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Entry
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- *173360 - SERPIN PEPTIDASE INHIBITOR, CLADE E (NEXIN, PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1), MEMBER 1; SERPINE1
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*173360</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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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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<a href="#molecularGenetics">Molecular Genetics</a>
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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/173360">Table View</a>
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</li>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></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 role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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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=ENSG00000106366;t=ENST00000223095" 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=5054" 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=173360" 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=ENSG00000106366;t=ENST00000223095" 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_000602,NM_001386456,NM_001386457,NM_001386458,NM_001386459,NM_001386460,NM_001386461,NM_001386462,NM_001386463,NM_001386464,NM_001386465,NM_001386466" 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_000602" 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=173360" 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=01418&isoform_id=01418_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/SERPINE1" 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/31147,35245,35261,35264,35272,129576,189542,189578,386996,386997,755747,1335247,5630083,5650696,5650698,5650699,5679572,5679573,5679574,10835159,14326588,14790036,119570580,119570581,119570582,221039424,221041958,221042070,221045838,229612376,311426285,1727530113,1895975948,1895975956,1895975965,1895975978,1895975991,1895976005,1895976010,1895976016,1895976031,1895976045,1896034491" 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/P05121" 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=5054" 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=ENSG00000106366;t=ENST00000223095" 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=SERPINE1" 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=SERPINE1" 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+5054" 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/SERPINE1" 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:5054" 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/5054" 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=chr7&hgg_gene=ENST00000223095.5&hgg_start=101127104&hgg_end=101139247&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:8583" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:8583" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/serpine1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=173360[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=173360[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/ENSG00000106366" 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=SERPINE1" 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=SERPINE1" 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=SERPINE1" 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=SERPINE1&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/PA261" 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:8583" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0024293.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:97608" 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/SERPINE1#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:97608" 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/5054/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=5054" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00005643;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00005643 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00005644;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00005644 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00005649;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00005649 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-070912-60" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:5054" 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=SERPINE1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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173360
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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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SERPIN PEPTIDASE INHIBITOR, CLADE E (NEXIN, PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1), MEMBER 1; SERPINE1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
PLASMINOGEN ACTIVATOR INHIBITOR 1; PAI1<br />
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ENDOTHELIAL PLASMINOGEN ACTIVATOR INHIBITOR
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</span>
|
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</h4>
|
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</div>
|
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</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SERPINE1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SERPINE1</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/7/527?start=-3&limit=10&highlight=527">7q22.1</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:101127104-101139247&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'})">7:101,127,104-101,139,247</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<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">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=613329" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
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</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/527?start=-3&limit=10&highlight=527">
|
|
7q22.1
|
|
</a>
|
|
</span>
|
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</td>
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
{Transcription of plasminogen activator inhibitor, modulator of}
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<p>The SERPINE1 gene encodes endothelial plasminogen activator inhibitor-1 (PAI1), a member of the serine protease inhibitor family that inhibits tissue-type plasminogen activator (PLAT; <a href="/entry/173370">173370</a>) and urokinase-type plasminogen activator (PLAU; <a href="/entry/191840">191840</a>). PLAT and PLAU proteolytically activate plasminogen (PLG; <a href="/entry/173350">173350</a>) into plasmin, which breaks down fibrin clots. Thus, SERPINE1 negatively regulates fibrinolysis and impairs the dissolution of clots (<a href="#11" class="mim-tip-reference" title="Ginsburg, D., Zeheb, R., Yang, A. Y., Rafferty, U. M., Andreasen, P. A., Nielsen, L., Dano, K., Lebo, R. V., Gelehrter, T. D. <strong>cDNA cloning of human plasminogen activator-inhibitor from endothelial cells.</strong> J. Clin. Invest. 78: 1673-1680, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3097076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3097076</a>] [<a href="https://doi.org/10.1172/JCI112761" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3097076">Ginsburg et al., 1986</a>; <a href="#23" class="mim-tip-reference" title="Mehta, R., Shapiro, A. D. <strong>Plasminogen activator inhibitor type 1 deficiency.</strong> Haemophilia 14: 1255-1260, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19141166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19141166</a>] [<a href="https://doi.org/10.1111/j.1365-2516.2008.01834.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19141166">Mehta and Shapiro, 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19141166+3097076" 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="#11" class="mim-tip-reference" title="Ginsburg, D., Zeheb, R., Yang, A. Y., Rafferty, U. M., Andreasen, P. A., Nielsen, L., Dano, K., Lebo, R. V., Gelehrter, T. D. <strong>cDNA cloning of human plasminogen activator-inhibitor from endothelial cells.</strong> J. Clin. Invest. 78: 1673-1680, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3097076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3097076</a>] [<a href="https://doi.org/10.1172/JCI112761" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3097076">Ginsburg et al. (1986)</a> isolated a full-length cDNA corresponding to plasminogen activator inhibitor-1 from a human umbilical vein endothelial cell lambda gt11 cDNA library. By nucleotide sequence analysis, they found that the PAI1 cDNA encodes a preprotein containing 402 amino acids, with the mature protein predicted to be 379 amino acids long with a predicted nonglycosylated molecular mass of 42.7 kD. The deduced amino acid sequence showed extensive homology with members of the serine protease inhibitor family (SERPINs), including angiotensinogen (AGT; <a href="/entry/106150">106150</a>), alpha-1-antitrypsin (PI; <a href="/entry/107400">107400</a>), and antithrombin III (AT3; <a href="/entry/107300">107300</a>). However, plasminogen activator inhibitor-2 (PAI2, SERPINB2; <a href="/entry/173390">173390</a>) was found to be less similar to PAI1 than it is to the other proteins of this group, suggesting that PAI1 and PAI2 did not arise by gene duplication event. Northern blot analysis showed that cultured human umbilical vein endothelial cells contained 2 PAI1 mRNA species, both encoded by a single gene, differing by 1 kb in the 3-prime untranslated region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3097076" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Ny, T., Sawdey, M., Lawrence, D., Millan, J. L., Loskutoff, D. J. <strong>Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor.</strong> Proc. Nat. Acad. Sci. 83: 6776-6780, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3092219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3092219</a>] [<a href="https://doi.org/10.1073/pnas.83.18.6776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3092219">Ny et al. (1986)</a> cloned and sequenced a cDNA for the endothelial cell type of PAI, which shows beta-mobility when analyzed by electrophoresis. The mature 379-residue protein had a calculated unglycosylated molecular mass of 42.7 kD. Three putative glycosylation sites were found. The deduced amino acid sequence showed 30% homology with alpha-1-antitrypsin and antithrombin III. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3092219" 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="#20" class="mim-tip-reference" title="Loskutoff, D. J., Linders, M., Keijer, J., Veerman, H., van Heerikhuizen, H., Pannekoek, H. <strong>Structure of the human plasminogen activator inhibitor 1 gene: nonrandom distribution of introns.</strong> Biochemistry 26: 3763-3768, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2820474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2820474</a>] [<a href="https://doi.org/10.1021/bi00387a004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2820474">Loskutoff et al. (1987)</a> demonstrated that the SERPINE1 gene is approximately 12.2 kb long and contains 9 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2820474" 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="#34" class="mim-tip-reference" title="van Zonneveld, A.-J., Curriden, S. A., Loskutoff, D. J. <strong>Type 1 plasminogen activator inhibitor gene: functional analysis and glucocorticoid regulation of its promoter.</strong> Proc. Nat. Acad. Sci. 85: 5525-5529, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2840665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2840665</a>] [<a href="https://doi.org/10.1073/pnas.85.15.5525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2840665">Van Zonneveld et al. (1988)</a> isolated and sequenced the promoter of the SERPINE1 gene. They used promoter-deletion mapping experiments and fusion of promoter fragments to a heterologous gene to show the existence of an enhancer-like glucocorticoid responsive element within the regions between nucleotides -305 and 75. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2840665" 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="#11" class="mim-tip-reference" title="Ginsburg, D., Zeheb, R., Yang, A. Y., Rafferty, U. M., Andreasen, P. A., Nielsen, L., Dano, K., Lebo, R. V., Gelehrter, T. D. <strong>cDNA cloning of human plasminogen activator-inhibitor from endothelial cells.</strong> J. Clin. Invest. 78: 1673-1680, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3097076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3097076</a>] [<a href="https://doi.org/10.1172/JCI112761" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3097076">Ginsburg et al. (1986)</a> assigned the SERPINE1 gene to human chromosome 7 by hybridization with sorted chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3097076" 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="#16" class="mim-tip-reference" title="Klinger, K. W., Winqvist, R., Andreasen, P. A., Stuart, N., Stanislovitis, P., Schwartz, R., Doherty, R., Alitalo, K., Blasi, F., Dano, K. <strong>Regional mapping of the plasminogen activator inhibitor type 1 gene to 7q21.3-q22 and assignment to the CF linkage group. (Abstract)</strong> Cytogenet. Cell Genet. 46: 640 only, 1987."None>Klinger et al. (1987)</a> stated that the gene resides on 7q, about 3 cM from erythropoietin (EPO; <a href="/entry/133170">133170</a>) and the alpha-2 chain of type I collagen (COL1A2; <a href="/entry/120160">120160</a>), which are very tightly linked. It is between these loci and about 20 cM away from the cystic fibrosis locus (CFTR; <a href="/entry/602421">602421</a>).</p><p>By Southern blot analysis of a panel of human/mouse somatic cell hybrids, <a href="#17" class="mim-tip-reference" title="Klinger, K. W., Winqvist, R., Andreasen, P. A., Stuart, N., Stanislovitis, P., Watkins, P., Schwartz, R., Doherty, R., Alitalo, K., Blasi, F., Dano, K. <strong>Assignment of the human plasminogen activator inhibitor type 1 (PAI-1) gene to 7q21.3-q22 and genetic linkage to markers on chromosome 7. (Abstract)</strong> Am. J. Hum. Genet. 41: A172 only, 1987."None>Klinger et al. (1987)</a> assigned the PAI1 gene to 7cen-q32; by in situ hybridization, they localized it to 7q21.3-q22. They also mapped its location in relation to other markers on chromosome 7 by means of family studies. <a href="#33" class="mim-tip-reference" title="Schwartz, C. E., Stanislovitis, P., Phelan, M. C., Klinger, K., Taylor, H. A., Stevenson, R. E. <strong>Deletion mapping of plasminogen activator inhibitor, type I (PLANH1) and beta-glucuronidase (GUSB) in 7q21-q22.</strong> Cytogenet. Cell Genet. 56: 152-153, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2055109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2055109</a>] [<a href="https://doi.org/10.1159/000133073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2055109">Schwartz et al. (1991)</a> localized the PAI1 gene to 7q22.1-q22.3 by study of an interstitial deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2055109" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#13" class="mim-tip-reference" title="Halleux, C. M., Declerck, P. J., Tran, S. L., Detry, R., Brichard, S. M. <strong>Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines.</strong> J. Clin. Endocr. Metab. 84: 4097-4105, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10566656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10566656</a>] [<a href="https://doi.org/10.1210/jcem.84.11.6127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10566656">Halleux et al. (1999)</a> investigated the hormonal control of PAI1 gene expression and secretion in cultured human adipose tissue. They focused on the effects of glucocorticoids, insulin, cAMP, and catecholamines in explants from the omental region. The addition of dexamethasone to the culture medium increased PAI1 secretion in a time-dependent manner for up to 24 hours. The stimulation by the glucocorticoid was preceded by a 2-fold rise in PAI1 mRNA levels between 4 to 8 hours of culture. The authors concluded that there is reciprocal regulation of PAI1 by dexamethasone (positive effector) and cAMP/catecholamines (negative effectors) in cultured human adipose tissue. The stimulation by glucocorticoids could contribute to enhanced production of PAI1 by adipose tissue and high plasma levels of PAI1 associated with central obesity and thereby be a link between this disorder and cardiovascular disease. Impaired inhibition by catecholamines could also contribute, because in vivo adipose tissue responses to these hormones are usually blunted in obese individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10566656" 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="#3" class="mim-tip-reference" title="Crandall, D. L., Busler, D. E., McHendry-Rinde, B., Groeling, T. M., Kral, J. G. <strong>Autocrine regulation of human preadipocyte migration by plasminogen activator inhibitor-1.</strong> J. Clin. Endocr. Metab. 85: 2609-2614, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10902815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10902815</a>] [<a href="https://doi.org/10.1210/jcem.85.7.6678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10902815">Crandall et al. (2000)</a> investigated the role of PAI1 in cultures of human preadipocytes from men and women of various ages and body mass indexes. Human preadipocytes expressed the mRNA for PAI1 and released significant quantities of PAI1 protein into the medium. <a href="#3" class="mim-tip-reference" title="Crandall, D. L., Busler, D. E., McHendry-Rinde, B., Groeling, T. M., Kral, J. G. <strong>Autocrine regulation of human preadipocyte migration by plasminogen activator inhibitor-1.</strong> J. Clin. Endocr. Metab. 85: 2609-2614, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10902815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10902815</a>] [<a href="https://doi.org/10.1210/jcem.85.7.6678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10902815">Crandall et al. (2000)</a> noted that PAI1 regulates motility through the interaction of vitronectin with its receptor, the integrin alpha-V-beta-3 (see <a href="/entry/193210">193210</a>), and they identified this receptor in human preadipocytes. Transwells with active PAI1 prevented preadipocyte migration. Vitronectin was identified in homogenates of the stromal-vascular fraction of human adipose tissue, but was absent from human adipocytes and cultured preadipocytes. The authors concluded that human preadipocyte migration is regulated through the endogenous expression of PAI1 and alpha-V-beta-3 integrin, a novel autocrine mechanism for potentially regulating cell cluster formation in adipogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10902815" 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="#19" class="mim-tip-reference" title="Kohler, H. P., Grant, P. J. <strong>Plasminogen-activator inhibitor type 1 and coronary artery disease.</strong> New Eng. J. Med. 342: 1792-1801, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10853003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10853003</a>] [<a href="https://doi.org/10.1056/NEJM200006153422406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10853003">Kohler and Grant (2000)</a> discussed the mechanisms regulating the production and action of PAI1 and the role of gene-environment interactions in controlling fibrinolysis. They also discussed how these factors may affect the risk of artherothrombosis in persons with coronary artery disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10853003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Maemura, K., de la Monte, S. M., Chin, M. T., Layne, M. D., Hsieh, C.-M., Yet, S.-F., Perrella, M. A., Lee, M.-E. <strong>CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression.</strong> J. Biol. Chem. 275: 36847-36851, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11018023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11018023</a>] [<a href="https://doi.org/10.1074/jbc.C000629200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11018023">Maemura et al. (2000)</a> stated that expression of PAI1 in humans is under circadian control, with peak expression in the morning. They found that peak Pai1 expression in mouse, a nocturnal animal, occurred in the evening in both brain and peripheral tissues. Expression of PAI1 in human umbilical vein endothelial cells was elevated by CLOCK (<a href="/entry/601851">601851</a>), the master circadian regulator, and CLOCK-dependent PAI1 expression was enhanced by coexpression of CLIF (ARNTL2; <a href="/entry/614517">614517</a>) with CLOCK. PER2 (<a href="/entry/603426">603426</a>) and CRY1 (<a href="/entry/601933">601933</a>) antagonized CLOCK/CLIF-dependent PAI1 expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11018023" 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>Aldosterone enhances angiotensin II (see <a href="/entry/106150">106150</a>)-induced PAI1 expression in vitro. <a href="#32" class="mim-tip-reference" title="Sawathiparnich, P., Murphey, L. J., Kumar, S., Vaughan, D. E., Brown, N. J. <strong>Effect of combined AT(1) receptor and aldosterone receptor antagonism on plasminogen activator inhibitor-1.</strong> J. Clin. Endocr. Metab. 88: 3867-3873, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12915681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12915681</a>] [<a href="https://doi.org/10.1210/jc.2003-030374" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12915681">Sawathiparnich et al. (2003)</a> tested the hypothesis that angiotensin II type 1 and aldosterone receptor (<a href="/entry/600983">600983</a>) antagonism interact to decrease PAI1 in humans. Effects of candesartan, spironolactone, or combined candesartan/spironolactone on mean arterial pressure, endocrine, and fibrinolytic variables were measured in 18 normotensive subjects in whom the renin (<a href="/entry/179820">179820</a>)-angiotensin-aldosterone system was activated by furosemide. This study evidenced an interactive effect of endogenous angiotensin II and aldosterone on PAI1 production in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12915681" 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="#29" class="mim-tip-reference" title="Patel, N., Tahara, S. M., Malik, P., Kalra, V. K. <strong>Involvement of miR-30c and miR-301a in immediate induction of plasminogen activator inhibitor-1 by placental growth factor in human pulmonary endothelial cells.</strong> Biochem. J. 434: 473-482, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21175428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21175428</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21175428[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/10.1042/BJ20101585" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21175428">Patel et al. (2011)</a> had previously determined that PIGF (<a href="/entry/600153">600153</a>) stimulation increased expression of PAI1 mRNA in human pulmonary microvascular endothelial cells by recruiting the transcription factors HIF1-alpha (HIF1A; <a href="/entry/603348">603348</a>) and AP1 (see <a href="/entry/165160">165160</a>) to the PAI1 promoter. The authors found that the 3-prime UTR of PAI1 mRNA contained binding sites for MIR301A (<a href="/entry/615675">615675</a>) and MIR30C. Knockdown of these miRNAs increased PAI1 mRNA levels, whereas overexpression of pre-MIR30C or pre-MIR301A attenuated PIGF-dependent induction of PAI1 mRNA and protein. <a href="#29" class="mim-tip-reference" title="Patel, N., Tahara, S. M., Malik, P., Kalra, V. K. <strong>Involvement of miR-30c and miR-301a in immediate induction of plasminogen activator inhibitor-1 by placental growth factor in human pulmonary endothelial cells.</strong> Biochem. J. 434: 473-482, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21175428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21175428</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21175428[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/10.1042/BJ20101585" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21175428">Patel et al. (2011)</a> found that plasma from patients with sickle cell anemia (<a href="/entry/603903">603903</a>), who exhibit elevated PIGF due to increased compensatory erythropoiesis, showed reduced MIR30C and MIR301A content compared with healthy control plasma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21175428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Plasminogen Activator Inhibitor-1 Deficiency</em></strong></p><p>
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In affected members of an Amish family with lifelong bleeding tendency after trauma or surgery due to PAI1 deficiency (<a href="/entry/613329">613329</a>), Fay et al. (<a href="#9" class="mim-tip-reference" title="Fay, W. P., Shapiro, A. D., Shih, J. L., Schleef, R. R., Ginsburg, D. <strong>Complete deficiency of plasminogen-activator inhibitor type I due to a frameshift mutation.</strong> New Eng. J. Med. 327: 1729-1733, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1435917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1435917</a>] [<a href="https://doi.org/10.1056/NEJM199212103272406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1435917">1992</a>, <a href="#8" class="mim-tip-reference" title="Fay, W. P., Parker, A. C., Condrey, L. R., Shapiro, A. D. <strong>Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene.</strong> Blood 90: 204-208, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207454</a>]" pmid="9207454">1997</a>) identified a homozygous frameshift mutation in the PAI1 gene (<a href="#0001">173360.0001</a>). The mutation resulted in complete loss of protein function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9207454+1435917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Possible Role in Thrombosis</em></strong></p><p>
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Thrombophilia (see <a href="/entry/188050">188050</a>) due to increased concentration of plasminogen activator inhibitor was described by <a href="#24" class="mim-tip-reference" title="Nilsson, I. M., Ljungner, H., Tengborn, L. <strong>Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor.</strong> Brit. Med. J. 290: 1453-1456, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3922531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3922531</a>] [<a href="https://doi.org/10.1136/bmj.290.6480.1453" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3922531">Nilsson et al. (1985)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3922531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="Nilsson, I. M., Tengborn, L. <strong>Impaired fibrinolysis: new evidence in relation to thrombosis. In: Jespersen, J.; Kluft, C.; Korsgaard, O. (eds.): Clinical Aspects of Fibrinolysis and Thrombolysis.</strong> Esbjerg: South Jutland Univ. Press (pub.) 1983. Pp. 273-291."None>Nilsson and Tengborn (1983)</a> restudied 2 members of a large family in which venous thrombosis was thought originally to have been associated with deficiency of tissue plasminogen activator (PLAT; <a href="/entry/173370">173370</a>). After venous occlusion, both members of the family showed a normal release of tissue plasminogen activator antigen, but low tissue plasminogen activator concentrations as measured by fibrin plates. The plasma contained 50 times more tissue plasminogen activator inhibitor than normal. However, <a href="#5" class="mim-tip-reference" title="Engesser, L., Brommer, E. J. P., Kluft, C., Briet, E. <strong>Elevated plasminogen activator inhibitor (PAI), a cause of thrombophilia? A study in 203 patients with familial or sporadic venous thrombophilia.</strong> Thromb. Haemost. 62: 673-680, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2683188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2683188</a>]" pmid="2683188">Engesser et al. (1989)</a> was unable to establish a connection between familial thrombophilia and inherited, persistent elevation of plasma PAI. The cause-and-effect relationship between increased PAI1 and thrombosis was supported by the observations of <a href="#6" class="mim-tip-reference" title="Erickson, L. A., Fici, G. J., Lund, J. E., Boyle, T. P., Polites, H. G., Marotti, K. R. <strong>Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene.</strong> Nature 346: 74-76, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2366866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2366866</a>] [<a href="https://doi.org/10.1038/346074a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2366866">Erickson et al. (1990)</a> who, from studies of mice transgenic for this gene, concluded that elevated levels contribute to the development of venous but not arterial occlusions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2683188+2366866" 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="#30" class="mim-tip-reference" title="Patrassi, G. M., Sartori, M. T., Saggiorato, G., Boeri, G., Girolami, A. <strong>Familial thrombophila (sic) associated with high levels of plasminogen activator inhibitor.</strong> Fibrinolysis 6: 99-103, 1992."None>Patrassi et al. (1992)</a> presented a family with several presumably affected members with thrombophilia associated with high levels of plasminogen activator inhibitor.</p><p><a href="#12" class="mim-tip-reference" title="Glueck, C. J., Glueck, H. I., Mieczkowski, L., Tracy, T., Speirs, J., Stroop, D. <strong>Familial high plasminogen activator inhibitor with hypofibrinolysis, a new pathophysiologic cause of osteonecrosis?</strong> Thromb. Haemost. 69: 460-465, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8322268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8322268</a>]" pmid="8322268">Glueck et al. (1993)</a> found familial high levels of PAI1 with hypofibrinolysis as the cause of osteonecrosis of both hips and a shoulder in a 29-year-old white male. High functional PAI1 and PAI1 antigen appeared to be inherited as an autosomal dominant trait. They referred to other patients with idiopathic osteonecrosis and a high level of PAI1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8322268" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a cross-sectional study of patients with a history of myocardial infarction (MI) and in matched controls from the Finnish population, <a href="#28" class="mim-tip-reference" title="Pastinen, T., Perola, M., Niini, P., Terwilliger, J., Salomaa, V., Vartiainen, E., Peltonen, L., Syvanen, A.-C. <strong>Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population.</strong> Hum. Molec. Genet. 7: 1453-1462, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9700201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9700201</a>] [<a href="https://doi.org/10.1093/hmg/7.9.1453" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9700201">Pastinen et al. (1998)</a> analyzed common variants of 8 genes implicated previously as risk factors for coronary heart disease or MI. Multiplex genotyping of the target genes was performed using a specific and efficient array-based minisequencing system. The authors identified an association between increased risk of MI and a SNP in the PAI1 gene with a 4G allele (<a href="#0002">173360.0002</a>) (p less than 0.05) and with a Pl(A2) allele of the glycoprotein IIIa (ITGB3; <a href="/entry/173470">173470</a>) gene (p less than 0.01) MI in the Finnish population. The combined effect of these risk alleles conferred a high risk for the development of MI (odds ratio (OR) = 4.5, p = 0.001), which was particularly prominent in male subjects (OR = 6.4, p = 0.0005). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9700201" 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="#37" class="mim-tip-reference" title="Yamada, Y., Izawa, H., Ichihara, S., Takatsu, F., Ishihara, H., Hirayama, H., Sone, T., Tanaka, M., Yokota, M. <strong>Prediction of the risk of myocardial infarction from polymorphisms in candidate genes.</strong> New Eng. J. Med. 347: 1916-1923, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12477941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12477941</a>] [<a href="https://doi.org/10.1056/NEJMoa021445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12477941">Yamada et al. (2002)</a> performed a 2-stage association study of myocardial infarction using 112 polymorphisms of 71 candidate genes in 2,819 unrelated Japanese patients with myocardial infarction and 2,242 unrelated Japanese controls. In an initial screening in 909 of the subjects with myocardial infarction, 19 polymorphisms were selected in men and 18 in women, after adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia. In a large-scale study involving the selected polymorphisms and the remaining 4,152 subjects, similar logistic regression analysis revealed that the risk of myocardial infarction was significantly associated with the 1019C-T polymorphism in the GJA4 gene (<a href="/entry/121012">121012</a>) in men and the -1171 5A/6A polymorphism in the MMP3 gene (<a href="/entry/185250">185250</a>) and the -668 4G/5G polymorphism in the PAI1 gene in women. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12477941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Carmeliet, P., Moons, L., Lijnen, R., Janssens, S., Lupu, F., Collen, D., Gerard, R. D. <strong>Inhibitory role of plasminogen activator inhibitor-1 in arterial wound healing and neointima formation: a gene targeting and gene transfer study in mice.</strong> Circulation 96: 3180-3191, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9386191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9386191</a>] [<a href="https://doi.org/10.1161/01.cir.96.9.3180" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9386191">Carmeliet et al. (1997)</a> provided direct evidence to support a role for Pai1 in arterial wound healing in mice. Techniques of arterial injury were designed in mice to model the histologic changes seen in human arteries following angioplasty and surgical anastomosis. Pai1 gene knockout mice underwent arterial injury followed by adenovirus-mediated Pai1 gene transfer by intravenous injection. Recombinant Pai1 expression was demonstrated in injured arteries and was found to inhibit neointima formation by inhibiting smooth muscle cell migration. <a href="#2" class="mim-tip-reference" title="Carmeliet, P., Moons, L., Lijnen, R., Janssens, S., Lupu, F., Collen, D., Gerard, R. D. <strong>Inhibitory role of plasminogen activator inhibitor-1 in arterial wound healing and neointima formation: a gene targeting and gene transfer study in mice.</strong> Circulation 96: 3180-3191, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9386191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9386191</a>] [<a href="https://doi.org/10.1161/01.cir.96.9.3180" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9386191">Carmeliet et al. (1997)</a> suggested that this may have implications for the treatment of arterial stenosis in humans following surgical intervention. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9386191" 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>Carbon monoxide can arrest cellular respiration, but paradoxically, it is synthesized endogenously by heme oxygenase-1 (HMOX1; <a href="/entry/141250">141250</a>) in response to ischemic stress. Hmox1 -/- mice exhibited lethal ischemic lung injury, but were rescued from death by inhaled carbon monoxide. Carbon monoxide drove ischemic protection by activating soluble guanylate cyclase and thereby suppressed hypoxic induction of Pai1 in mononuclear phagocytes, which reduced accrual of microvascular fibrin. Carbon monoxide-mediated ischemic protection observed in wildtype mice was lost in Pai1-null mice. <a href="#10" class="mim-tip-reference" title="Fujita, T., Toda, K., Karimova, A., Yan, S.-F., Naka, Y., Yet, S.-F., Pinsky, D. J. <strong>Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis.</strong> Nature Med. 7: 598-604, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11329062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11329062</a>] [<a href="https://doi.org/10.1038/87929" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11329062">Fujita et al. (2001)</a> concluded that their data established a fundamental link between carbon monoxide and prevention of ischemic injury based on the ability of carbon monoxide to derepress the fibrinolytic axis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11329062" 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="#38" class="mim-tip-reference" title="Yamamoto, K., Takeshita, K., Shimokawa, T., Yi, H., Isobe, K., Loskutoff, D. J., Saito, H. <strong>Plasminogen activator inhibitor-1 is a major stress-regulated gene: implications for stress-induced thrombosis in aged individuals.</strong> Proc. Nat. Acad. Sci. 99: 890-895, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11792849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11792849</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11792849[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.022608799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11792849">Yamamoto et al. (2002)</a> investigated the stress-induced changes in murine Pai1 gene expression to study the role of this inhibitor in the development of stress-induced hypercoagulability. Restraint stress led to a dramatic induction of plasma Pai1 antigen and of tissue Pai1 mRNA, with maximum induction in adipose tissues. In situ hybridization analysis of the stressed mice revealed that strong signals for Pai1 mRNA were localized to hepatocytes, renal tubular epithelial cells, adrenomedullar chromaffin cells, neural cells in the paraaortic sympathetic ganglion, vascular smooth muscle cells, and adipocytes, but not to endothelial cells. Thus, stress induced Pai1 gene expression in a tissue-specific and cell-specific manner. The induction of Pai1 mRNA by restraint stress was greater than that observed for heat shock protein (see <a href="/entry/140550">140550</a>), a typical stress protein, suggesting that Pai1 is one of the most highly induced stress proteins. The magnitude of induction of Pai1 mRNA by stress increased markedly with age, and this increase in Pai1 correlated with tissue thrombosis in the older stressed mice. Moreover, much less tissue thrombosis was induced by restraint stress in young and aged Pai1-deficient mice compared with age-matched wildtype mice. These results suggested that the large induction of PAI1 by stress increases the risk for thrombosis in older populations, and that adipose tissue may be involved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11792849" 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="#1" class="mim-tip-reference" title="Boccaccio, C., Sabatino, G., Medico, E., Girolami, F., Follenzi, A., Reato, G., Sottile, A., Naldini, L., Comoglio, P. M. <strong>The MET oncogene drives a genetic programme linking cancer to haemostasis. (Letter)</strong> Nature 434: 396-400, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772665</a>] [<a href="https://doi.org/10.1038/nature03357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15772665">Boccaccio et al. (2005)</a> developed a mouse model of sporadic tumorigenesis in which they targeted the activated human MET oncogene (<a href="/entry/164860">164860</a>) to adult liver. They observed slowly progressive hepatocarcinogenesis, which was preceded and accompanied by a disseminated intravascular coagulation (DIC)-like thrombohemorrhagic syndrome. Genomewide expression profiling of MLP29 cells transduced with the activated MET oncogene revealed prominent upregulation of PAI1 and cyclooxygenase-2 (PTGS2; <a href="/entry/600262">600262</a>), and in vivo administration of a PAI1 or COX2 inhibitor slowed the evolution towards full-blown DIC. <a href="#1" class="mim-tip-reference" title="Boccaccio, C., Sabatino, G., Medico, E., Girolami, F., Follenzi, A., Reato, G., Sottile, A., Naldini, L., Comoglio, P. M. <strong>The MET oncogene drives a genetic programme linking cancer to haemostasis. (Letter)</strong> Nature 434: 396-400, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772665</a>] [<a href="https://doi.org/10.1038/nature03357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15772665">Boccaccio et al. (2005)</a> concluded that this study provided the first direct genetic evidence for the link between oncogene activation and hemostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15772665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 9-year-old girl from an Old Order Amish community with plasminogen activator inhibitor-1 deficiency (<a href="/entry/613329">613329</a>), <a href="#9" class="mim-tip-reference" title="Fay, W. P., Shapiro, A. D., Shih, J. L., Schleef, R. R., Ginsburg, D. <strong>Complete deficiency of plasminogen-activator inhibitor type I due to a frameshift mutation.</strong> New Eng. J. Med. 327: 1729-1733, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1435917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1435917</a>] [<a href="https://doi.org/10.1056/NEJM199212103272406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1435917">Fay et al. (1992)</a> identified a homozygous 2-bp insertion (4977insTA) in exon 5 of the SERPINE1 gene, resulting in a frameshift, premature termination, and a nonfunctional protein. The TA insertion represented a duplication of nucleotides 4975 and 4976. The predicted protein product lacked the 169 C-terminal amino acids of the wildtype protein, including the active center, arg346-met347. The proposita had had several episodes of major hemorrhage, all in response to trauma or surgery. In the Amish pedigree of the proband reported by <a href="#9" class="mim-tip-reference" title="Fay, W. P., Shapiro, A. D., Shih, J. L., Schleef, R. R., Ginsburg, D. <strong>Complete deficiency of plasminogen-activator inhibitor type I due to a frameshift mutation.</strong> New Eng. J. Med. 327: 1729-1733, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1435917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1435917</a>] [<a href="https://doi.org/10.1056/NEJM199212103272406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1435917">Fay et al. (1992)</a>, <a href="#8" class="mim-tip-reference" title="Fay, W. P., Parker, A. C., Condrey, L. R., Shapiro, A. D. <strong>Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene.</strong> Blood 90: 204-208, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207454</a>]" pmid="9207454">Fay et al. (1997)</a> identified 7 additional homozygous mutation carriers. Clinical manifestations were restricted to abnormal bleeding, which was observed only after trauma or surgery. The spectrum of bleeding patterns included intracranial and joint bleeding after mild trauma, delayed surgical bleeding, severe menstrual bleeding, and frequent bruising. Fibrinolysis inhibitors, including epsilon-aminocaproic acid and tranexamic acid, were effective in treating and preventing bleeding episodes. Other than abnormal bleeding, no significant developmental or other abnormalities were observed in homozygotes. The 19 identified heterozygotes did not display abnormal bleeding, even after trauma or surgery. The observations of <a href="#8" class="mim-tip-reference" title="Fay, W. P., Parker, A. C., Condrey, L. R., Shapiro, A. D. <strong>Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene.</strong> Blood 90: 204-208, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207454</a>]" pmid="9207454">Fay et al. (1997)</a> supported the hypothesis that the primary function of plasminogen activator inhibitor-1 in vivo is to regulate vascular fibrinolysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9207454+1435917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1799762 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1799762;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=rs1799762" 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=rs1799762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#4" class="mim-tip-reference" title="Dawson, S. J., Wiman, B., Hamsten, A., Green, F., Humphries, S., Henney, A. M. <strong>The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells.</strong> J. Biol. Chem. 268: 10739-10745, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8388372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8388372</a>]" pmid="8388372">Dawson et al. (1993)</a> and <a href="#7" class="mim-tip-reference" title="Eriksson, P., Kallin, B., van t'Hooft, F. M., Bavhenolm. P., Hamsten, A. <strong>Allelic-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction.</strong> Proc. Nat. Acad. Sci. 92: 1851-1855, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7892190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7892190</a>] [<a href="https://doi.org/10.1073/pnas.92.6.1851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7892190">Eriksson et al. (1995)</a> demonstrated that raised PAI1 plasma levels are related to a 1-bp guanine deletion/insertion (4G/5G) polymorphism in the promoter of the PAI1 gene. The 4G allele is associated with higher plasma PAI1 transcription and activity. Although both alleles bind a transcriptional activator, the 5G allele also binds a repressor protein to an overlapping binding site. In the absence of bound repressor, the 4G allele is associated with an increased basal level of PAI1 transcription. <a href="#7" class="mim-tip-reference" title="Eriksson, P., Kallin, B., van t'Hooft, F. M., Bavhenolm. P., Hamsten, A. <strong>Allelic-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction.</strong> Proc. Nat. Acad. Sci. 92: 1851-1855, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7892190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7892190</a>] [<a href="https://doi.org/10.1073/pnas.92.6.1851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7892190">Eriksson et al. (1995)</a> found that the prevalence of the 4G allele was significantly higher in patients with myocardial infarction before the age of 45 (allele frequency of 0.63) than in population-based controls (allele frequency of 0.53). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8388372+7892190" 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="#22" class="mim-tip-reference" title="Margaglione, M., Cappucci, G., Colaizzo, D., Giuliani, N., Vecchione, G., Grandone, E., Pennelli, O., Di Minno, G. <strong>The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease.</strong> Arterioscler. Thromb. Vasc. Biol. 18: 152-156, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9484978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9484978</a>] [<a href="https://doi.org/10.1161/01.atv.18.2.152" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9484978">Margaglione et al. (1998)</a> investigated the relationship between the PAI1 4G/5G polymorphism in 1,179 healthy employees and the occurrence of coronary artery disease in their first-degree relatives. The group with a first-degree relative who had suffered from a coronary ischemic episode had a higher number of homozygotes for the 4G allele compared with subjects without such a family history (odds ratio = 1.62). The frequency of the 4G allele was abnormally high in individuals with a family history who also had a higher body mass index and total cholesterol levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9484978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of the PAI1 genotype in 175 children with meningococcal disease, <a href="#15" class="mim-tip-reference" title="Hermans, P. W. M., Hibberd, M. L., Booy, R., Daramola, O., Hazelzet, J. A., de Groot, R., Levin, M., Meningococcal Research Group. <strong>4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease.</strong> Lancet 354: 556-560, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10470700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10470700</a>] [<a href="https://doi.org/10.1016/s0140-6736(99)02220-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10470700">Hermans et al. (1999)</a> found that the median PAI1 concentration in children who died was substantially higher than that in survivors. Patients with the 4G/4G genotype had significantly higher PAI1 concentrations than those with the 4G/5G or 5G/5G genotype and had an increased risk of death. The findings suggested that impaired fibrinolysis is an important factor in the pathophysiology of meningococcal sepsis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10470700" 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>Some patients infected with Neisseria meningitidis develop septic shock accompanied by fibrin deposition and microthrombus formation in various organs, whereas others develop bacteremia or meningitis without septic shock. <a href="#35" class="mim-tip-reference" title="Westendorp, R. G. J., Hottenga, J.-J., Slagboom, P. E. <strong>Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock.</strong> Lancet 354: 561-563, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10470701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10470701</a>] [<a href="https://doi.org/10.1016/S0140-6736(98)09376-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10470701">Westendorp et al. (1999)</a> investigated whether genetic differences in the fibrinolytic system influence the development of meningococcal septic shock. They studied 50 patients who survived meningococcal infection, and 131 controls from the same geographic region. Because they had no information on genotypes of patients who died, they also genotyped 183 first-degree relatives of a consecutive series of patients with meningococcal infection for the 4G/5G deletion/insertion polymorphism in the promoter region of the PAI1 gene. The 4G allele was associated with increased gene transcription in cell lines in vitro and with increased PAI1 concentrations in carriers in vivo. The allele frequencies of 4G and 5G were similar between patients and controls. However, the 4G/4G genotype was present in only 9% of relatives of patients with meningitis compared with 36% of relatives of patients with septic shock. Patients whose relatives were carriers of the 4G/4G genotype had a 6-fold higher risk of developing septic shock than meningitis compared with all other genotypes. <a href="#35" class="mim-tip-reference" title="Westendorp, R. G. J., Hottenga, J.-J., Slagboom, P. E. <strong>Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock.</strong> Lancet 354: 561-563, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10470701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10470701</a>] [<a href="https://doi.org/10.1016/S0140-6736(98)09376-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10470701">Westendorp et al. (1999)</a> concluded that variation in the PAI1 gene does not affect the probability of contracting meningococcal infection, but does influence the development of septic shock. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10470701" 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>Preeclampsia is associated with thrombosis of the intervillous or spiral artery of the placenta. <a href="#36" class="mim-tip-reference" title="Yamada, N., Arinami, T., Yamakawa-Kobayashi, K., Watanabe, H., Sohda, S., Hamada, H., Kubo, T., Hamaguchi, H. <strong>The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia.</strong> J. Hum. Genet. 45: 138-141, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10807538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10807538</a>] [<a href="https://doi.org/10.1007/s100380050200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10807538">Yamada et al. (2000)</a> assessed the association between preeclampsia and the 4G/5G polymorphism of the PAI1 gene in 115 preeclampsia patients, 210 pregnant controls, and 298 healthy volunteer controls. The frequency of homozygotes for the 4G allele was significantly higher in the patients than in the control pregnant women or healthy volunteers. The 4G allele frequency was also significantly higher in the patients than in the 2 control groups. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10807538" 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="#39" class="mim-tip-reference" title="Yoon, S., Tromp, G., Vongpunsawad, S., Ronkainen, A., Juvonen, T., Kuivaniemi, H. <strong>Genetic analysis of MMP3, and PAI-1 in Finnish patients with abdominal aortic or intracranial aneurysms.</strong> Biochem. Biophys. Res. Commun. 265: 563-568, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10558909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10558909</a>] [<a href="https://doi.org/10.1006/bbrc.1999.1721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10558909">Yoon et al. (1999)</a> found no association between the 4G/5G polymorphism in the PAI1 gene and abdominal aortic aneurysm in a study of 47 Finnish patients and 74 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10558909" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The 5G variant of PAI1 is associated with less inhibition of the plasminogen activators and, consequently, increased conversion of plasminogen to plasmin and increased activation of matrix metalloproteinases. Thus, patients with this variant may be more at risk of the development of abdominal aortic aneurysm (AAA; <a href="/entry/100070">100070</a>). <a href="#31" class="mim-tip-reference" title="Rossaak, J. I., van Rij, A. M., Jones, G. T., Harris, E. L. <strong>Association of the 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor-1 with abdominal aortic aneurysms.</strong> J. Vasc. Surg. 31: 1026-1032, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10805895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10805895</a>] [<a href="https://doi.org/10.1067/mva.2000.104589" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10805895">Rossaak et al. (2000)</a> studied the ratios of the 4G:5G genotypes in 190 patients with AAA, including 39 patients with strong family histories, and 163 controls. The frequency of the 4G:5G alleles in the AAA population and in the control population was 0.6:0.4. However, 26% of patients with familial AAA were homozygous 5G compared with 13% of the control population. The 4G allele frequency was 0.47 in the familial AAAs, compared with 0.62 in the nonfamilial patients (P = 0.02) and 0.61 in the control population (P = 0.03). The association of the 5G homozygous genotype with familial AAA questioned the idea that atherosclerosis causes AAAs. Whereas the 4G variant of PAI1 shows a protective role in AAA, it is undesirable in the context of coronary artery disease and atherosclerosis (<a href="#14" class="mim-tip-reference" title="Harris, E. L. <strong>Personal Communication.</strong> Dunedin, New Zealand 11/27/2001."None>Harris, 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10805895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 PLASMINOGEN ACTIVATOR INHIBITOR-1 DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs6092 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6092;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs6092?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs6092" 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=rs6092" 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=RCV000014541 OR RCV001530150 OR RCV001723567 OR RCV001807002 OR RCV003982840" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014541, RCV001530150, RCV001723567, RCV001807002, RCV003982840" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014541...</a>
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<p>In a Chinese patient with PAI1 deficiency (<a href="/entry/613329">613329</a>), <a href="#40" class="mim-tip-reference" title="Zhang, Z. Y., Wang, Z. Y., Dong, N. Z., Bai, X., Zhang, W., Ruan, C. G. <strong>A case of deficiency of plasma plasminogen activator inhibitor-1 related to ala15thr mutation in its signal peptide.</strong> Blood Coagul. Fibrinolysis. 16: 79-84, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15650551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15650551</a>] [<a href="https://doi.org/10.1097/00001721-200501000-00013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15650551">Zhang et al. (2005)</a> identified a heterozygous 4497G-A transition in exon 2 of the SERPINE1 gene, resulting in an ala15-to-thr (A15T) substitution in the signal peptide. He had lifelong bleeding episodes in response to trauma and surgery, and laboratory studies showed decreased activity and antigen levels of PAI1 to about 10% of normal controls. His father, who was also heterozygous for the A15T mutation, had moderately reduced PAI1 antigen and activity, but had no bleeding history. Although his mother did not carry a mutation in the coding region of the SERPINE1 gene, <a href="#40" class="mim-tip-reference" title="Zhang, Z. Y., Wang, Z. Y., Dong, N. Z., Bai, X., Zhang, W., Ruan, C. G. <strong>A case of deficiency of plasma plasminogen activator inhibitor-1 related to ala15thr mutation in its signal peptide.</strong> Blood Coagul. Fibrinolysis. 16: 79-84, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15650551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15650551</a>] [<a href="https://doi.org/10.1097/00001721-200501000-00013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15650551">Zhang et al. (2005)</a> concluded that she likely had a heterozygous mutation in another region of the gene, since she had moderately decreased PAI1 antigen and activity similar to the heterozygous father. In vitro functional expression studies of the A15T mutant showed PAI1 activity at about 70% of wildtype, and the authors suggested that the mutation impaired the secretion of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15650551" 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="#Klinger1987" class="mim-tip-reference" title="Klinger, K. W., Winqvist, R., Riccio, A., Andreasen, P. A., Sartorio, R., Nielsen, L. S., Stuart, N., Stanislovitis, P., Watkins, P., Douglas, R., Grzeschik, K.-H., Alitalo, K., Blasi, F., Dano, K. <strong>Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis.</strong> Proc. Nat. Acad. Sci. 84: 8548-8552, 1987.">Klinger et al. (1987)</a>; <a href="#Pannekoek1986" class="mim-tip-reference" title="Pannekoek, H., Veerman, H., Lambers, H., Diergaarde, P., Verweij, C. L., van Zonneveld, A.-J., van Mourik, J. A. <strong>Endothelial plasminogen activator inhibitor (PAI): a new member of the serpin gene family.</strong> EMBO J. 5: 2539-2544, 1986.">Pannekoek et al. (1986)</a>
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Boccaccio, C., Sabatino, G., Medico, E., Girolami, F., Follenzi, A., Reato, G., Sottile, A., Naldini, L., Comoglio, P. M.
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<strong>The MET oncogene drives a genetic programme linking cancer to haemostasis. (Letter)</strong>
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Nature 434: 396-400, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772665</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15772665" 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/nature03357" target="_blank">Full Text</a>]
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Carmeliet, P., Moons, L., Lijnen, R., Janssens, S., Lupu, F., Collen, D., Gerard, R. D.
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<strong>Inhibitory role of plasminogen activator inhibitor-1 in arterial wound healing and neointima formation: a gene targeting and gene transfer study in mice.</strong>
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Circulation 96: 3180-3191, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9386191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9386191</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9386191" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1161/01.cir.96.9.3180" target="_blank">Full Text</a>]
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Crandall, D. L., Busler, D. E., McHendry-Rinde, B., Groeling, T. M., Kral, J. G.
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<strong>Autocrine regulation of human preadipocyte migration by plasminogen activator inhibitor-1.</strong>
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J. Clin. Endocr. Metab. 85: 2609-2614, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10902815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10902815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10902815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Dawson, S. J., Wiman, B., Hamsten, A., Green, F., Humphries, S., Henney, A. M.
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<strong>The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells.</strong>
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J. Biol. Chem. 268: 10739-10745, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8388372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8388372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8388372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Engesser, L., Brommer, E. J. P., Kluft, C., Briet, E.
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<strong>Elevated plasminogen activator inhibitor (PAI), a cause of thrombophilia? A study in 203 patients with familial or sporadic venous thrombophilia.</strong>
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Thromb. Haemost. 62: 673-680, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2683188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2683188</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2683188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Erickson1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Erickson, L. A., Fici, G. J., Lund, J. E., Boyle, T. P., Polites, H. G., Marotti, K. R.
|
|
<strong>Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene.</strong>
|
|
Nature 346: 74-76, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2366866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2366866</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2366866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/346074a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Eriksson1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eriksson, P., Kallin, B., van t'Hooft, F. M., Bavhenolm. P., Hamsten, A.
|
|
<strong>Allelic-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction.</strong>
|
|
Proc. Nat. Acad. Sci. 92: 1851-1855, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7892190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7892190</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7892190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.92.6.1851" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Fay1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fay, W. P., Parker, A. C., Condrey, L. R., Shapiro, A. D.
|
|
<strong>Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene.</strong>
|
|
Blood 90: 204-208, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207454</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9207454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Fay1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fay, W. P., Shapiro, A. D., Shih, J. L., Schleef, R. R., Ginsburg, D.
|
|
<strong>Complete deficiency of plasminogen-activator inhibitor type I due to a frameshift mutation.</strong>
|
|
New Eng. J. Med. 327: 1729-1733, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1435917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1435917</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1435917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM199212103272406" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Fujita2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fujita, T., Toda, K., Karimova, A., Yan, S.-F., Naka, Y., Yet, S.-F., Pinsky, D. J.
|
|
<strong>Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis.</strong>
|
|
Nature Med. 7: 598-604, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11329062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11329062</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11329062" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/87929" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Ginsburg1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ginsburg, D., Zeheb, R., Yang, A. Y., Rafferty, U. M., Andreasen, P. A., Nielsen, L., Dano, K., Lebo, R. V., Gelehrter, T. D.
|
|
<strong>cDNA cloning of human plasminogen activator-inhibitor from endothelial cells.</strong>
|
|
J. Clin. Invest. 78: 1673-1680, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3097076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3097076</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3097076" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112761" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Glueck1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Glueck, C. J., Glueck, H. I., Mieczkowski, L., Tracy, T., Speirs, J., Stroop, D.
|
|
<strong>Familial high plasminogen activator inhibitor with hypofibrinolysis, a new pathophysiologic cause of osteonecrosis?</strong>
|
|
Thromb. Haemost. 69: 460-465, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8322268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8322268</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8322268" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Halleux1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Halleux, C. M., Declerck, P. J., Tran, S. L., Detry, R., Brichard, S. M.
|
|
<strong>Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines.</strong>
|
|
J. Clin. Endocr. Metab. 84: 4097-4105, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10566656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10566656</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10566656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.84.11.6127" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Harris2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Harris, E. L.
|
|
<strong>Personal Communication.</strong>
|
|
Dunedin, New Zealand 11/27/2001.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Hermans1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hermans, P. W. M., Hibberd, M. L., Booy, R., Daramola, O., Hazelzet, J. A., de Groot, R., Levin, M., Meningococcal Research Group.
|
|
<strong>4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease.</strong>
|
|
Lancet 354: 556-560, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10470700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10470700</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10470700" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(99)02220-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Klinger1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Klinger, K. W., Winqvist, R., Andreasen, P. A., Stuart, N., Stanislovitis, P., Schwartz, R., Doherty, R., Alitalo, K., Blasi, F., Dano, K.
|
|
<strong>Regional mapping of the plasminogen activator inhibitor type 1 gene to 7q21.3-q22 and assignment to the CF linkage group. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 640 only, 1987.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Klinger1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Klinger, K. W., Winqvist, R., Andreasen, P. A., Stuart, N., Stanislovitis, P., Watkins, P., Schwartz, R., Doherty, R., Alitalo, K., Blasi, F., Dano, K.
|
|
<strong>Assignment of the human plasminogen activator inhibitor type 1 (PAI-1) gene to 7q21.3-q22 and genetic linkage to markers on chromosome 7. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 41: A172 only, 1987.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Klinger1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Klinger, K. W., Winqvist, R., Riccio, A., Andreasen, P. A., Sartorio, R., Nielsen, L. S., Stuart, N., Stanislovitis, P., Watkins, P., Douglas, R., Grzeschik, K.-H., Alitalo, K., Blasi, F., Dano, K.
|
|
<strong>Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis.</strong>
|
|
Proc. Nat. Acad. Sci. 84: 8548-8552, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2891140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2891140</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2891140" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.84.23.8548" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Kohler2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kohler, H. P., Grant, P. J.
|
|
<strong>Plasminogen-activator inhibitor type 1 and coronary artery disease.</strong>
|
|
New Eng. J. Med. 342: 1792-1801, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10853003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10853003</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10853003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM200006153422406" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Loskutoff1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Loskutoff, D. J., Linders, M., Keijer, J., Veerman, H., van Heerikhuizen, H., Pannekoek, H.
|
|
<strong>Structure of the human plasminogen activator inhibitor 1 gene: nonrandom distribution of introns.</strong>
|
|
Biochemistry 26: 3763-3768, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2820474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2820474</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2820474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1021/bi00387a004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Maemura2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maemura, K., de la Monte, S. M., Chin, M. T., Layne, M. D., Hsieh, C.-M., Yet, S.-F., Perrella, M. A., Lee, M.-E.
|
|
<strong>CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression.</strong>
|
|
J. Biol. Chem. 275: 36847-36851, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11018023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11018023</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11018023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.C000629200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Margaglione1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Margaglione, M., Cappucci, G., Colaizzo, D., Giuliani, N., Vecchione, G., Grandone, E., Pennelli, O., Di Minno, G.
|
|
<strong>The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease.</strong>
|
|
Arterioscler. Thromb. Vasc. Biol. 18: 152-156, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9484978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9484978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9484978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1161/01.atv.18.2.152" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Mehta2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mehta, R., Shapiro, A. D.
|
|
<strong>Plasminogen activator inhibitor type 1 deficiency.</strong>
|
|
Haemophilia 14: 1255-1260, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19141166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19141166</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19141166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2516.2008.01834.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Nilsson1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nilsson, I. M., Ljungner, H., Tengborn, L.
|
|
<strong>Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor.</strong>
|
|
Brit. Med. J. 290: 1453-1456, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3922531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3922531</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3922531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bmj.290.6480.1453" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Nilsson1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nilsson, I. M., Tengborn, L.
|
|
<strong>Impaired fibrinolysis: new evidence in relation to thrombosis. In: Jespersen, J.; Kluft, C.; Korsgaard, O. (eds.): Clinical Aspects of Fibrinolysis and Thrombolysis.</strong>
|
|
Esbjerg: South Jutland Univ. Press (pub.) 1983. Pp. 273-291.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Ny1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ny, T., Sawdey, M., Lawrence, D., Millan, J. L., Loskutoff, D. J.
|
|
<strong>Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor.</strong>
|
|
Proc. Nat. Acad. Sci. 83: 6776-6780, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3092219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3092219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3092219" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.83.18.6776" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Pannekoek1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pannekoek, H., Veerman, H., Lambers, H., Diergaarde, P., Verweij, C. L., van Zonneveld, A.-J., van Mourik, J. A.
|
|
<strong>Endothelial plasminogen activator inhibitor (PAI): a new member of the serpin gene family.</strong>
|
|
EMBO J. 5: 2539-2544, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2430793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2430793</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2430793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1986.tb04532.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Pastinen1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pastinen, T., Perola, M., Niini, P., Terwilliger, J., Salomaa, V., Vartiainen, E., Peltonen, L., Syvanen, A.-C.
|
|
<strong>Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population.</strong>
|
|
Hum. Molec. Genet. 7: 1453-1462, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9700201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9700201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9700201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/7.9.1453" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Patel2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Patel, N., Tahara, S. M., Malik, P., Kalra, V. K.
|
|
<strong>Involvement of miR-30c and miR-301a in immediate induction of plasminogen activator inhibitor-1 by placental growth factor in human pulmonary endothelial cells.</strong>
|
|
Biochem. J. 434: 473-482, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21175428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21175428</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21175428[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=21175428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1042/BJ20101585" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Patrassi1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Patrassi, G. M., Sartori, M. T., Saggiorato, G., Boeri, G., Girolami, A.
|
|
<strong>Familial thrombophila (sic) associated with high levels of plasminogen activator inhibitor.</strong>
|
|
Fibrinolysis 6: 99-103, 1992.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Rossaak2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rossaak, J. I., van Rij, A. M., Jones, G. T., Harris, E. L.
|
|
<strong>Association of the 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor-1 with abdominal aortic aneurysms.</strong>
|
|
J. Vasc. Surg. 31: 1026-1032, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10805895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10805895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10805895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1067/mva.2000.104589" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Sawathiparnich2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sawathiparnich, P., Murphey, L. J., Kumar, S., Vaughan, D. E., Brown, N. J.
|
|
<strong>Effect of combined AT(1) receptor and aldosterone receptor antagonism on plasminogen activator inhibitor-1.</strong>
|
|
J. Clin. Endocr. Metab. 88: 3867-3873, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12915681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12915681</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12915681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2003-030374" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Schwartz1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schwartz, C. E., Stanislovitis, P., Phelan, M. C., Klinger, K., Taylor, H. A., Stevenson, R. E.
|
|
<strong>Deletion mapping of plasminogen activator inhibitor, type I (PLANH1) and beta-glucuronidase (GUSB) in 7q21-q22.</strong>
|
|
Cytogenet. Cell Genet. 56: 152-153, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2055109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2055109</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2055109" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000133073" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="van Zonneveld1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van Zonneveld, A.-J., Curriden, S. A., Loskutoff, D. J.
|
|
<strong>Type 1 plasminogen activator inhibitor gene: functional analysis and glucocorticoid regulation of its promoter.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 5525-5529, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2840665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2840665</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2840665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.85.15.5525" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Westendorp1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Westendorp, R. G. J., Hottenga, J.-J., Slagboom, P. E.
|
|
<strong>Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock.</strong>
|
|
Lancet 354: 561-563, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10470701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10470701</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10470701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/S0140-6736(98)09376-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Yamada2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamada, N., Arinami, T., Yamakawa-Kobayashi, K., Watanabe, H., Sohda, S., Hamada, H., Kubo, T., Hamaguchi, H.
|
|
<strong>The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia.</strong>
|
|
J. Hum. Genet. 45: 138-141, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10807538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10807538</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10807538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s100380050200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Yamada2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamada, Y., Izawa, H., Ichihara, S., Takatsu, F., Ishihara, H., Hirayama, H., Sone, T., Tanaka, M., Yokota, M.
|
|
<strong>Prediction of the risk of myocardial infarction from polymorphisms in candidate genes.</strong>
|
|
New Eng. J. Med. 347: 1916-1923, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12477941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12477941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12477941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa021445" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Yamamoto2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamamoto, K., Takeshita, K., Shimokawa, T., Yi, H., Isobe, K., Loskutoff, D. J., Saito, H.
|
|
<strong>Plasminogen activator inhibitor-1 is a major stress-regulated gene: implications for stress-induced thrombosis in aged individuals.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 890-895, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11792849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11792849</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11792849[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=11792849" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.022608799" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Yoon1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yoon, S., Tromp, G., Vongpunsawad, S., Ronkainen, A., Juvonen, T., Kuivaniemi, H.
|
|
<strong>Genetic analysis of MMP3, and PAI-1 in Finnish patients with abdominal aortic or intracranial aneurysms.</strong>
|
|
Biochem. Biophys. Res. Commun. 265: 563-568, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10558909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10558909</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10558909" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.1999.1721" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Zhang2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, Z. Y., Wang, Z. Y., Dong, N. Z., Bai, X., Zhang, W., Ruan, C. G.
|
|
<strong>A case of deficiency of plasma plasminogen activator inhibitor-1 related to ala15thr mutation in its signal peptide.</strong>
|
|
Blood Coagul. Fibrinolysis. 16: 79-84, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15650551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15650551</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15650551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00001721-200501000-00013" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
</ol>
|
|
|
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|
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|
|
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|
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Patricia A. Hartz - updated : 03/18/2014
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Patricia A. Hartz - updated : 2/29/2012<br>Cassandra L. Kniffin - reorganized : 4/1/2010<br>Cassandra L. Kniffin - updated : 3/30/2010<br>Marla J. F. O'Neill - updated : 3/23/2005<br>John A. Phillips, III - updated : 10/12/2004<br>Victor A. McKusick - updated : 12/17/2002<br>Victor A. McKusick - updated : 2/6/2002<br>Victor A. McKusick - updated : 1/8/2002<br>Victor A. McKusick - updated : 12/14/2001<br>Ada Hamosh - updated : 5/2/2001<br>John A. Phillips, III - updated : 2/9/2001<br>John A. Phillips, III - updated : 10/2/2000<br>Victor A. McKusick - updated : 7/14/2000<br>Victor A. McKusick - updated : 6/12/2000<br>Victor A. McKusick - updated : 11/1/1999<br>Victor A. McKusick - updated : 2/10/1999<br>Victor A. McKusick - updated : 9/17/1998<br>Paul Brennan - updated : 1/16/1998<br>Victor A. McKusick - updated : 9/29/1997
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Creation Date:
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Victor A. McKusick : 12/15/1986
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alopez : 08/01/2023
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carol : 08/25/2016<br>carol : 08/24/2016<br>mgross : 03/18/2014<br>carol : 9/17/2013<br>mgross : 3/2/2012<br>terry : 2/29/2012<br>ckniffin : 2/23/2012<br>carol : 4/1/2010<br>carol : 4/1/2010<br>ckniffin : 3/30/2010<br>joanna : 3/19/2010<br>wwang : 8/28/2006<br>carol : 12/13/2005<br>alopez : 12/13/2005<br>alopez : 3/23/2005<br>alopez : 3/23/2005<br>alopez : 10/12/2004<br>tkritzer : 12/20/2002<br>tkritzer : 12/19/2002<br>terry : 12/17/2002<br>ckniffin : 6/5/2002<br>terry : 3/13/2002<br>mgross : 2/11/2002<br>terry : 2/6/2002<br>alopez : 1/8/2002<br>alopez : 1/7/2002<br>terry : 12/14/2001<br>alopez : 5/3/2001<br>terry : 5/2/2001<br>alopez : 2/22/2001<br>terry : 2/9/2001<br>mgross : 10/13/2000<br>terry : 10/2/2000<br>terry : 7/14/2000<br>mcapotos : 6/27/2000<br>terry : 6/12/2000<br>carol : 11/9/1999<br>terry : 11/1/1999<br>terry : 5/5/1999<br>mgross : 3/10/1999<br>carol : 2/17/1999<br>mgross : 2/16/1999<br>mgross : 2/12/1999<br>terry : 2/10/1999<br>carol : 12/13/1998<br>carol : 9/21/1998<br>terry : 9/17/1998<br>carol : 1/16/1998<br>jenny : 10/1/1997<br>terry : 9/29/1997<br>mark : 4/3/1997<br>mimadm : 1/14/1995<br>carol : 7/6/1993<br>carol : 12/8/1992<br>carol : 10/22/1992<br>carol : 10/20/1992<br>carol : 7/2/1992
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<strong>*</strong> 173360
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SERPIN PEPTIDASE INHIBITOR, CLADE E (NEXIN, PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1), MEMBER 1; SERPINE1
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PLASMINOGEN ACTIVATOR INHIBITOR 1; PAI1<br />
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ENDOTHELIAL PLASMINOGEN ACTIVATOR INHIBITOR
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<strong><em>HGNC Approved Gene Symbol: SERPINE1</em></strong>
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Cytogenetic location: 7q22.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 7:101,127,104-101,139,247 </span>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Phenotype
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Phenotype <br /> MIM number
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7q22.1
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{Transcription of plasminogen activator inhibitor, modulator of}
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3
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Plasminogen activator inhibitor-1 deficiency
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613329
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Autosomal dominant; Autosomal recessive
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The SERPINE1 gene encodes endothelial plasminogen activator inhibitor-1 (PAI1), a member of the serine protease inhibitor family that inhibits tissue-type plasminogen activator (PLAT; 173370) and urokinase-type plasminogen activator (PLAU; 191840). PLAT and PLAU proteolytically activate plasminogen (PLG; 173350) into plasmin, which breaks down fibrin clots. Thus, SERPINE1 negatively regulates fibrinolysis and impairs the dissolution of clots (Ginsburg et al., 1986; Mehta and Shapiro, 2008). </p>
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<strong>Cloning and Expression</strong>
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<p>Ginsburg et al. (1986) isolated a full-length cDNA corresponding to plasminogen activator inhibitor-1 from a human umbilical vein endothelial cell lambda gt11 cDNA library. By nucleotide sequence analysis, they found that the PAI1 cDNA encodes a preprotein containing 402 amino acids, with the mature protein predicted to be 379 amino acids long with a predicted nonglycosylated molecular mass of 42.7 kD. The deduced amino acid sequence showed extensive homology with members of the serine protease inhibitor family (SERPINs), including angiotensinogen (AGT; 106150), alpha-1-antitrypsin (PI; 107400), and antithrombin III (AT3; 107300). However, plasminogen activator inhibitor-2 (PAI2, SERPINB2; 173390) was found to be less similar to PAI1 than it is to the other proteins of this group, suggesting that PAI1 and PAI2 did not arise by gene duplication event. Northern blot analysis showed that cultured human umbilical vein endothelial cells contained 2 PAI1 mRNA species, both encoded by a single gene, differing by 1 kb in the 3-prime untranslated region. </p><p>Ny et al. (1986) cloned and sequenced a cDNA for the endothelial cell type of PAI, which shows beta-mobility when analyzed by electrophoresis. The mature 379-residue protein had a calculated unglycosylated molecular mass of 42.7 kD. Three putative glycosylation sites were found. The deduced amino acid sequence showed 30% homology with alpha-1-antitrypsin and antithrombin III. </p>
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<strong>Gene Structure</strong>
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<p>Loskutoff et al. (1987) demonstrated that the SERPINE1 gene is approximately 12.2 kb long and contains 9 exons. </p><p>Van Zonneveld et al. (1988) isolated and sequenced the promoter of the SERPINE1 gene. They used promoter-deletion mapping experiments and fusion of promoter fragments to a heterologous gene to show the existence of an enhancer-like glucocorticoid responsive element within the regions between nucleotides -305 and 75. </p>
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<strong>Mapping</strong>
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<p>Ginsburg et al. (1986) assigned the SERPINE1 gene to human chromosome 7 by hybridization with sorted chromosomes. </p><p>Klinger et al. (1987) stated that the gene resides on 7q, about 3 cM from erythropoietin (EPO; 133170) and the alpha-2 chain of type I collagen (COL1A2; 120160), which are very tightly linked. It is between these loci and about 20 cM away from the cystic fibrosis locus (CFTR; 602421).</p><p>By Southern blot analysis of a panel of human/mouse somatic cell hybrids, Klinger et al. (1987) assigned the PAI1 gene to 7cen-q32; by in situ hybridization, they localized it to 7q21.3-q22. They also mapped its location in relation to other markers on chromosome 7 by means of family studies. Schwartz et al. (1991) localized the PAI1 gene to 7q22.1-q22.3 by study of an interstitial deletion. </p>
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<strong>Gene Function</strong>
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<p>Halleux et al. (1999) investigated the hormonal control of PAI1 gene expression and secretion in cultured human adipose tissue. They focused on the effects of glucocorticoids, insulin, cAMP, and catecholamines in explants from the omental region. The addition of dexamethasone to the culture medium increased PAI1 secretion in a time-dependent manner for up to 24 hours. The stimulation by the glucocorticoid was preceded by a 2-fold rise in PAI1 mRNA levels between 4 to 8 hours of culture. The authors concluded that there is reciprocal regulation of PAI1 by dexamethasone (positive effector) and cAMP/catecholamines (negative effectors) in cultured human adipose tissue. The stimulation by glucocorticoids could contribute to enhanced production of PAI1 by adipose tissue and high plasma levels of PAI1 associated with central obesity and thereby be a link between this disorder and cardiovascular disease. Impaired inhibition by catecholamines could also contribute, because in vivo adipose tissue responses to these hormones are usually blunted in obese individuals. </p><p>Crandall et al. (2000) investigated the role of PAI1 in cultures of human preadipocytes from men and women of various ages and body mass indexes. Human preadipocytes expressed the mRNA for PAI1 and released significant quantities of PAI1 protein into the medium. Crandall et al. (2000) noted that PAI1 regulates motility through the interaction of vitronectin with its receptor, the integrin alpha-V-beta-3 (see 193210), and they identified this receptor in human preadipocytes. Transwells with active PAI1 prevented preadipocyte migration. Vitronectin was identified in homogenates of the stromal-vascular fraction of human adipose tissue, but was absent from human adipocytes and cultured preadipocytes. The authors concluded that human preadipocyte migration is regulated through the endogenous expression of PAI1 and alpha-V-beta-3 integrin, a novel autocrine mechanism for potentially regulating cell cluster formation in adipogenesis. </p><p>Kohler and Grant (2000) discussed the mechanisms regulating the production and action of PAI1 and the role of gene-environment interactions in controlling fibrinolysis. They also discussed how these factors may affect the risk of artherothrombosis in persons with coronary artery disease. </p><p>Maemura et al. (2000) stated that expression of PAI1 in humans is under circadian control, with peak expression in the morning. They found that peak Pai1 expression in mouse, a nocturnal animal, occurred in the evening in both brain and peripheral tissues. Expression of PAI1 in human umbilical vein endothelial cells was elevated by CLOCK (601851), the master circadian regulator, and CLOCK-dependent PAI1 expression was enhanced by coexpression of CLIF (ARNTL2; 614517) with CLOCK. PER2 (603426) and CRY1 (601933) antagonized CLOCK/CLIF-dependent PAI1 expression. </p><p>Aldosterone enhances angiotensin II (see 106150)-induced PAI1 expression in vitro. Sawathiparnich et al. (2003) tested the hypothesis that angiotensin II type 1 and aldosterone receptor (600983) antagonism interact to decrease PAI1 in humans. Effects of candesartan, spironolactone, or combined candesartan/spironolactone on mean arterial pressure, endocrine, and fibrinolytic variables were measured in 18 normotensive subjects in whom the renin (179820)-angiotensin-aldosterone system was activated by furosemide. This study evidenced an interactive effect of endogenous angiotensin II and aldosterone on PAI1 production in humans. </p><p>Patel et al. (2011) had previously determined that PIGF (600153) stimulation increased expression of PAI1 mRNA in human pulmonary microvascular endothelial cells by recruiting the transcription factors HIF1-alpha (HIF1A; 603348) and AP1 (see 165160) to the PAI1 promoter. The authors found that the 3-prime UTR of PAI1 mRNA contained binding sites for MIR301A (615675) and MIR30C. Knockdown of these miRNAs increased PAI1 mRNA levels, whereas overexpression of pre-MIR30C or pre-MIR301A attenuated PIGF-dependent induction of PAI1 mRNA and protein. Patel et al. (2011) found that plasma from patients with sickle cell anemia (603903), who exhibit elevated PIGF due to increased compensatory erythropoiesis, showed reduced MIR30C and MIR301A content compared with healthy control plasma. </p>
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<strong>Molecular Genetics</strong>
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<p><strong><em>Plasminogen Activator Inhibitor-1 Deficiency</em></strong></p><p>
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In affected members of an Amish family with lifelong bleeding tendency after trauma or surgery due to PAI1 deficiency (613329), Fay et al. (1992, 1997) identified a homozygous frameshift mutation in the PAI1 gene (173360.0001). The mutation resulted in complete loss of protein function. </p><p><strong><em>Possible Role in Thrombosis</em></strong></p><p>
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Thrombophilia (see 188050) due to increased concentration of plasminogen activator inhibitor was described by Nilsson et al. (1985). </p><p>Nilsson and Tengborn (1983) restudied 2 members of a large family in which venous thrombosis was thought originally to have been associated with deficiency of tissue plasminogen activator (PLAT; 173370). After venous occlusion, both members of the family showed a normal release of tissue plasminogen activator antigen, but low tissue plasminogen activator concentrations as measured by fibrin plates. The plasma contained 50 times more tissue plasminogen activator inhibitor than normal. However, Engesser et al. (1989) was unable to establish a connection between familial thrombophilia and inherited, persistent elevation of plasma PAI. The cause-and-effect relationship between increased PAI1 and thrombosis was supported by the observations of Erickson et al. (1990) who, from studies of mice transgenic for this gene, concluded that elevated levels contribute to the development of venous but not arterial occlusions. </p><p>Patrassi et al. (1992) presented a family with several presumably affected members with thrombophilia associated with high levels of plasminogen activator inhibitor.</p><p>Glueck et al. (1993) found familial high levels of PAI1 with hypofibrinolysis as the cause of osteonecrosis of both hips and a shoulder in a 29-year-old white male. High functional PAI1 and PAI1 antigen appeared to be inherited as an autosomal dominant trait. They referred to other patients with idiopathic osteonecrosis and a high level of PAI1. </p><p>In a cross-sectional study of patients with a history of myocardial infarction (MI) and in matched controls from the Finnish population, Pastinen et al. (1998) analyzed common variants of 8 genes implicated previously as risk factors for coronary heart disease or MI. Multiplex genotyping of the target genes was performed using a specific and efficient array-based minisequencing system. The authors identified an association between increased risk of MI and a SNP in the PAI1 gene with a 4G allele (173360.0002) (p less than 0.05) and with a Pl(A2) allele of the glycoprotein IIIa (ITGB3; 173470) gene (p less than 0.01) MI in the Finnish population. The combined effect of these risk alleles conferred a high risk for the development of MI (odds ratio (OR) = 4.5, p = 0.001), which was particularly prominent in male subjects (OR = 6.4, p = 0.0005). </p><p>Yamada et al. (2002) performed a 2-stage association study of myocardial infarction using 112 polymorphisms of 71 candidate genes in 2,819 unrelated Japanese patients with myocardial infarction and 2,242 unrelated Japanese controls. In an initial screening in 909 of the subjects with myocardial infarction, 19 polymorphisms were selected in men and 18 in women, after adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia. In a large-scale study involving the selected polymorphisms and the remaining 4,152 subjects, similar logistic regression analysis revealed that the risk of myocardial infarction was significantly associated with the 1019C-T polymorphism in the GJA4 gene (121012) in men and the -1171 5A/6A polymorphism in the MMP3 gene (185250) and the -668 4G/5G polymorphism in the PAI1 gene in women. </p>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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<p>Carmeliet et al. (1997) provided direct evidence to support a role for Pai1 in arterial wound healing in mice. Techniques of arterial injury were designed in mice to model the histologic changes seen in human arteries following angioplasty and surgical anastomosis. Pai1 gene knockout mice underwent arterial injury followed by adenovirus-mediated Pai1 gene transfer by intravenous injection. Recombinant Pai1 expression was demonstrated in injured arteries and was found to inhibit neointima formation by inhibiting smooth muscle cell migration. Carmeliet et al. (1997) suggested that this may have implications for the treatment of arterial stenosis in humans following surgical intervention. </p><p>Carbon monoxide can arrest cellular respiration, but paradoxically, it is synthesized endogenously by heme oxygenase-1 (HMOX1; 141250) in response to ischemic stress. Hmox1 -/- mice exhibited lethal ischemic lung injury, but were rescued from death by inhaled carbon monoxide. Carbon monoxide drove ischemic protection by activating soluble guanylate cyclase and thereby suppressed hypoxic induction of Pai1 in mononuclear phagocytes, which reduced accrual of microvascular fibrin. Carbon monoxide-mediated ischemic protection observed in wildtype mice was lost in Pai1-null mice. Fujita et al. (2001) concluded that their data established a fundamental link between carbon monoxide and prevention of ischemic injury based on the ability of carbon monoxide to derepress the fibrinolytic axis. </p><p>Yamamoto et al. (2002) investigated the stress-induced changes in murine Pai1 gene expression to study the role of this inhibitor in the development of stress-induced hypercoagulability. Restraint stress led to a dramatic induction of plasma Pai1 antigen and of tissue Pai1 mRNA, with maximum induction in adipose tissues. In situ hybridization analysis of the stressed mice revealed that strong signals for Pai1 mRNA were localized to hepatocytes, renal tubular epithelial cells, adrenomedullar chromaffin cells, neural cells in the paraaortic sympathetic ganglion, vascular smooth muscle cells, and adipocytes, but not to endothelial cells. Thus, stress induced Pai1 gene expression in a tissue-specific and cell-specific manner. The induction of Pai1 mRNA by restraint stress was greater than that observed for heat shock protein (see 140550), a typical stress protein, suggesting that Pai1 is one of the most highly induced stress proteins. The magnitude of induction of Pai1 mRNA by stress increased markedly with age, and this increase in Pai1 correlated with tissue thrombosis in the older stressed mice. Moreover, much less tissue thrombosis was induced by restraint stress in young and aged Pai1-deficient mice compared with age-matched wildtype mice. These results suggested that the large induction of PAI1 by stress increases the risk for thrombosis in older populations, and that adipose tissue may be involved. </p><p>Boccaccio et al. (2005) developed a mouse model of sporadic tumorigenesis in which they targeted the activated human MET oncogene (164860) to adult liver. They observed slowly progressive hepatocarcinogenesis, which was preceded and accompanied by a disseminated intravascular coagulation (DIC)-like thrombohemorrhagic syndrome. Genomewide expression profiling of MLP29 cells transduced with the activated MET oncogene revealed prominent upregulation of PAI1 and cyclooxygenase-2 (PTGS2; 600262), and in vivo administration of a PAI1 or COX2 inhibitor slowed the evolution towards full-blown DIC. Boccaccio et al. (2005) concluded that this study provided the first direct genetic evidence for the link between oncogene activation and hemostasis. </p>
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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>3 Selected Examples):</strong>
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</h4>
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<h4>
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<span class="mim-font">
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<strong>.0001 PLASMINOGEN ACTIVATOR INHIBITOR-1 DEFICIENCY</strong>
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</span>
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</h4>
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SERPINE1, 2-BP INS, 4977TA
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ClinVar: RCV000014539
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<p>In a 9-year-old girl from an Old Order Amish community with plasminogen activator inhibitor-1 deficiency (613329), Fay et al. (1992) identified a homozygous 2-bp insertion (4977insTA) in exon 5 of the SERPINE1 gene, resulting in a frameshift, premature termination, and a nonfunctional protein. The TA insertion represented a duplication of nucleotides 4975 and 4976. The predicted protein product lacked the 169 C-terminal amino acids of the wildtype protein, including the active center, arg346-met347. The proposita had had several episodes of major hemorrhage, all in response to trauma or surgery. In the Amish pedigree of the proband reported by Fay et al. (1992), Fay et al. (1997) identified 7 additional homozygous mutation carriers. Clinical manifestations were restricted to abnormal bleeding, which was observed only after trauma or surgery. The spectrum of bleeding patterns included intracranial and joint bleeding after mild trauma, delayed surgical bleeding, severe menstrual bleeding, and frequent bruising. Fibrinolysis inhibitors, including epsilon-aminocaproic acid and tranexamic acid, were effective in treating and preventing bleeding episodes. Other than abnormal bleeding, no significant developmental or other abnormalities were observed in homozygotes. The 19 identified heterozygotes did not display abnormal bleeding, even after trauma or surgery. The observations of Fay et al. (1997) supported the hypothesis that the primary function of plasminogen activator inhibitor-1 in vivo is to regulate vascular fibrinolysis. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 TRANSCRIPTION OF PLASMINOGEN ACTIVATOR INHIBITOR, MODULATOR OF</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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SEPINE1, 1-BP DEL/INS, 4G/5G
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<br />
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SNP: rs1799762,
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ClinVar: RCV000014540
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<span class="mim-text-font">
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<p>Dawson et al. (1993) and Eriksson et al. (1995) demonstrated that raised PAI1 plasma levels are related to a 1-bp guanine deletion/insertion (4G/5G) polymorphism in the promoter of the PAI1 gene. The 4G allele is associated with higher plasma PAI1 transcription and activity. Although both alleles bind a transcriptional activator, the 5G allele also binds a repressor protein to an overlapping binding site. In the absence of bound repressor, the 4G allele is associated with an increased basal level of PAI1 transcription. Eriksson et al. (1995) found that the prevalence of the 4G allele was significantly higher in patients with myocardial infarction before the age of 45 (allele frequency of 0.63) than in population-based controls (allele frequency of 0.53). </p><p>Margaglione et al. (1998) investigated the relationship between the PAI1 4G/5G polymorphism in 1,179 healthy employees and the occurrence of coronary artery disease in their first-degree relatives. The group with a first-degree relative who had suffered from a coronary ischemic episode had a higher number of homozygotes for the 4G allele compared with subjects without such a family history (odds ratio = 1.62). The frequency of the 4G allele was abnormally high in individuals with a family history who also had a higher body mass index and total cholesterol levels. </p><p>In a study of the PAI1 genotype in 175 children with meningococcal disease, Hermans et al. (1999) found that the median PAI1 concentration in children who died was substantially higher than that in survivors. Patients with the 4G/4G genotype had significantly higher PAI1 concentrations than those with the 4G/5G or 5G/5G genotype and had an increased risk of death. The findings suggested that impaired fibrinolysis is an important factor in the pathophysiology of meningococcal sepsis. </p><p>Some patients infected with Neisseria meningitidis develop septic shock accompanied by fibrin deposition and microthrombus formation in various organs, whereas others develop bacteremia or meningitis without septic shock. Westendorp et al. (1999) investigated whether genetic differences in the fibrinolytic system influence the development of meningococcal septic shock. They studied 50 patients who survived meningococcal infection, and 131 controls from the same geographic region. Because they had no information on genotypes of patients who died, they also genotyped 183 first-degree relatives of a consecutive series of patients with meningococcal infection for the 4G/5G deletion/insertion polymorphism in the promoter region of the PAI1 gene. The 4G allele was associated with increased gene transcription in cell lines in vitro and with increased PAI1 concentrations in carriers in vivo. The allele frequencies of 4G and 5G were similar between patients and controls. However, the 4G/4G genotype was present in only 9% of relatives of patients with meningitis compared with 36% of relatives of patients with septic shock. Patients whose relatives were carriers of the 4G/4G genotype had a 6-fold higher risk of developing septic shock than meningitis compared with all other genotypes. Westendorp et al. (1999) concluded that variation in the PAI1 gene does not affect the probability of contracting meningococcal infection, but does influence the development of septic shock. </p><p>Preeclampsia is associated with thrombosis of the intervillous or spiral artery of the placenta. Yamada et al. (2000) assessed the association between preeclampsia and the 4G/5G polymorphism of the PAI1 gene in 115 preeclampsia patients, 210 pregnant controls, and 298 healthy volunteer controls. The frequency of homozygotes for the 4G allele was significantly higher in the patients than in the control pregnant women or healthy volunteers. The 4G allele frequency was also significantly higher in the patients than in the 2 control groups. </p><p>Yoon et al. (1999) found no association between the 4G/5G polymorphism in the PAI1 gene and abdominal aortic aneurysm in a study of 47 Finnish patients and 74 controls. </p><p>The 5G variant of PAI1 is associated with less inhibition of the plasminogen activators and, consequently, increased conversion of plasminogen to plasmin and increased activation of matrix metalloproteinases. Thus, patients with this variant may be more at risk of the development of abdominal aortic aneurysm (AAA; 100070). Rossaak et al. (2000) studied the ratios of the 4G:5G genotypes in 190 patients with AAA, including 39 patients with strong family histories, and 163 controls. The frequency of the 4G:5G alleles in the AAA population and in the control population was 0.6:0.4. However, 26% of patients with familial AAA were homozygous 5G compared with 13% of the control population. The 4G allele frequency was 0.47 in the familial AAAs, compared with 0.62 in the nonfamilial patients (P = 0.02) and 0.61 in the control population (P = 0.03). The association of the 5G homozygous genotype with familial AAA questioned the idea that atherosclerosis causes AAAs. Whereas the 4G variant of PAI1 shows a protective role in AAA, it is undesirable in the context of coronary artery disease and atherosclerosis (Harris, 2001). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 PLASMINOGEN ACTIVATOR INHIBITOR-1 DEFICIENCY</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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SERPINE1, ALA15THR
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<br />
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SNP: rs6092,
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gnomAD: rs6092,
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ClinVar: RCV000014541, RCV001530150, RCV001723567, RCV001807002, RCV003982840
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Chinese patient with PAI1 deficiency (613329), Zhang et al. (2005) identified a heterozygous 4497G-A transition in exon 2 of the SERPINE1 gene, resulting in an ala15-to-thr (A15T) substitution in the signal peptide. He had lifelong bleeding episodes in response to trauma and surgery, and laboratory studies showed decreased activity and antigen levels of PAI1 to about 10% of normal controls. His father, who was also heterozygous for the A15T mutation, had moderately reduced PAI1 antigen and activity, but had no bleeding history. Although his mother did not carry a mutation in the coding region of the SERPINE1 gene, Zhang et al. (2005) concluded that she likely had a heterozygous mutation in another region of the gene, since she had moderately decreased PAI1 antigen and activity similar to the heterozygous father. In vitro functional expression studies of the A15T mutant showed PAI1 activity at about 70% of wildtype, and the authors suggested that the mutation impaired the secretion of the protein. </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>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Klinger et al. (1987); Pannekoek et al. (1986)
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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>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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Boccaccio, C., Sabatino, G., Medico, E., Girolami, F., Follenzi, A., Reato, G., Sottile, A., Naldini, L., Comoglio, P. M.
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<strong>The MET oncogene drives a genetic programme linking cancer to haemostasis. (Letter)</strong>
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Nature 434: 396-400, 2005.
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[PubMed: 15772665]
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[Full Text: https://doi.org/10.1038/nature03357]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Carmeliet, P., Moons, L., Lijnen, R., Janssens, S., Lupu, F., Collen, D., Gerard, R. D.
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<strong>Inhibitory role of plasminogen activator inhibitor-1 in arterial wound healing and neointima formation: a gene targeting and gene transfer study in mice.</strong>
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Circulation 96: 3180-3191, 1997.
|
|
|
|
|
|
[PubMed: 9386191]
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|
|
|
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[Full Text: https://doi.org/10.1161/01.cir.96.9.3180]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Crandall, D. L., Busler, D. E., McHendry-Rinde, B., Groeling, T. M., Kral, J. G.
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<strong>Autocrine regulation of human preadipocyte migration by plasminogen activator inhibitor-1.</strong>
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J. Clin. Endocr. Metab. 85: 2609-2614, 2000.
|
|
|
|
|
|
[PubMed: 10902815]
|
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|
|
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[Full Text: https://doi.org/10.1210/jcem.85.7.6678]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Dawson, S. J., Wiman, B., Hamsten, A., Green, F., Humphries, S., Henney, A. M.
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<strong>The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells.</strong>
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J. Biol. Chem. 268: 10739-10745, 1993.
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[PubMed: 8388372]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Engesser, L., Brommer, E. J. P., Kluft, C., Briet, E.
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<strong>Elevated plasminogen activator inhibitor (PAI), a cause of thrombophilia? A study in 203 patients with familial or sporadic venous thrombophilia.</strong>
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Thromb. Haemost. 62: 673-680, 1989.
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[PubMed: 2683188]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Erickson, L. A., Fici, G. J., Lund, J. E., Boyle, T. P., Polites, H. G., Marotti, K. R.
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<strong>Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene.</strong>
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Nature 346: 74-76, 1990.
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|
|
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[PubMed: 2366866]
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[Full Text: https://doi.org/10.1038/346074a0]
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</li>
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<li>
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<p class="mim-text-font">
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Eriksson, P., Kallin, B., van t'Hooft, F. M., Bavhenolm. P., Hamsten, A.
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<strong>Allelic-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction.</strong>
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Proc. Nat. Acad. Sci. 92: 1851-1855, 1995.
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[PubMed: 7892190]
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[Full Text: https://doi.org/10.1073/pnas.92.6.1851]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Fay, W. P., Parker, A. C., Condrey, L. R., Shapiro, A. D.
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<strong>Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene.</strong>
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Blood 90: 204-208, 1997.
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[PubMed: 9207454]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Fay, W. P., Shapiro, A. D., Shih, J. L., Schleef, R. R., Ginsburg, D.
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<strong>Complete deficiency of plasminogen-activator inhibitor type I due to a frameshift mutation.</strong>
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New Eng. J. Med. 327: 1729-1733, 1992.
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[PubMed: 1435917]
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[Full Text: https://doi.org/10.1056/NEJM199212103272406]
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</li>
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<li>
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<p class="mim-text-font">
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Fujita, T., Toda, K., Karimova, A., Yan, S.-F., Naka, Y., Yet, S.-F., Pinsky, D. J.
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<strong>Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis.</strong>
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Nature Med. 7: 598-604, 2001.
|
|
|
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[PubMed: 11329062]
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[Full Text: https://doi.org/10.1038/87929]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ginsburg, D., Zeheb, R., Yang, A. Y., Rafferty, U. M., Andreasen, P. A., Nielsen, L., Dano, K., Lebo, R. V., Gelehrter, T. D.
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<strong>cDNA cloning of human plasminogen activator-inhibitor from endothelial cells.</strong>
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J. Clin. Invest. 78: 1673-1680, 1986.
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[PubMed: 3097076]
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[Full Text: https://doi.org/10.1172/JCI112761]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Glueck, C. J., Glueck, H. I., Mieczkowski, L., Tracy, T., Speirs, J., Stroop, D.
|
|
<strong>Familial high plasminogen activator inhibitor with hypofibrinolysis, a new pathophysiologic cause of osteonecrosis?</strong>
|
|
Thromb. Haemost. 69: 460-465, 1993.
|
|
|
|
|
|
[PubMed: 8322268]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Halleux, C. M., Declerck, P. J., Tran, S. L., Detry, R., Brichard, S. M.
|
|
<strong>Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines.</strong>
|
|
J. Clin. Endocr. Metab. 84: 4097-4105, 1999.
|
|
|
|
|
|
[PubMed: 10566656]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.84.11.6127]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Harris, E. L.
|
|
<strong>Personal Communication.</strong>
|
|
Dunedin, New Zealand 11/27/2001.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hermans, P. W. M., Hibberd, M. L., Booy, R., Daramola, O., Hazelzet, J. A., de Groot, R., Levin, M., Meningococcal Research Group.
|
|
<strong>4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease.</strong>
|
|
Lancet 354: 556-560, 1999.
|
|
|
|
|
|
[PubMed: 10470700]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(99)02220-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Klinger, K. W., Winqvist, R., Andreasen, P. A., Stuart, N., Stanislovitis, P., Schwartz, R., Doherty, R., Alitalo, K., Blasi, F., Dano, K.
|
|
<strong>Regional mapping of the plasminogen activator inhibitor type 1 gene to 7q21.3-q22 and assignment to the CF linkage group. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 640 only, 1987.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Klinger, K. W., Winqvist, R., Andreasen, P. A., Stuart, N., Stanislovitis, P., Watkins, P., Schwartz, R., Doherty, R., Alitalo, K., Blasi, F., Dano, K.
|
|
<strong>Assignment of the human plasminogen activator inhibitor type 1 (PAI-1) gene to 7q21.3-q22 and genetic linkage to markers on chromosome 7. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 41: A172 only, 1987.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Klinger, K. W., Winqvist, R., Riccio, A., Andreasen, P. A., Sartorio, R., Nielsen, L. S., Stuart, N., Stanislovitis, P., Watkins, P., Douglas, R., Grzeschik, K.-H., Alitalo, K., Blasi, F., Dano, K.
|
|
<strong>Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis.</strong>
|
|
Proc. Nat. Acad. Sci. 84: 8548-8552, 1987.
|
|
|
|
|
|
[PubMed: 2891140]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.84.23.8548]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kohler, H. P., Grant, P. J.
|
|
<strong>Plasminogen-activator inhibitor type 1 and coronary artery disease.</strong>
|
|
New Eng. J. Med. 342: 1792-1801, 2000.
|
|
|
|
|
|
[PubMed: 10853003]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM200006153422406]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Loskutoff, D. J., Linders, M., Keijer, J., Veerman, H., van Heerikhuizen, H., Pannekoek, H.
|
|
<strong>Structure of the human plasminogen activator inhibitor 1 gene: nonrandom distribution of introns.</strong>
|
|
Biochemistry 26: 3763-3768, 1987.
|
|
|
|
|
|
[PubMed: 2820474]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1021/bi00387a004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maemura, K., de la Monte, S. M., Chin, M. T., Layne, M. D., Hsieh, C.-M., Yet, S.-F., Perrella, M. A., Lee, M.-E.
|
|
<strong>CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression.</strong>
|
|
J. Biol. Chem. 275: 36847-36851, 2000.
|
|
|
|
|
|
[PubMed: 11018023]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.C000629200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Margaglione, M., Cappucci, G., Colaizzo, D., Giuliani, N., Vecchione, G., Grandone, E., Pennelli, O., Di Minno, G.
|
|
<strong>The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease.</strong>
|
|
Arterioscler. Thromb. Vasc. Biol. 18: 152-156, 1998.
|
|
|
|
|
|
[PubMed: 9484978]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1161/01.atv.18.2.152]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mehta, R., Shapiro, A. D.
|
|
<strong>Plasminogen activator inhibitor type 1 deficiency.</strong>
|
|
Haemophilia 14: 1255-1260, 2008.
|
|
|
|
|
|
[PubMed: 19141166]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2516.2008.01834.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nilsson, I. M., Ljungner, H., Tengborn, L.
|
|
<strong>Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor.</strong>
|
|
Brit. Med. J. 290: 1453-1456, 1985.
|
|
|
|
|
|
[PubMed: 3922531]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bmj.290.6480.1453]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nilsson, I. M., Tengborn, L.
|
|
<strong>Impaired fibrinolysis: new evidence in relation to thrombosis. In: Jespersen, J.; Kluft, C.; Korsgaard, O. (eds.): Clinical Aspects of Fibrinolysis and Thrombolysis.</strong>
|
|
Esbjerg: South Jutland Univ. Press (pub.) 1983. Pp. 273-291.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ny, T., Sawdey, M., Lawrence, D., Millan, J. L., Loskutoff, D. J.
|
|
<strong>Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor.</strong>
|
|
Proc. Nat. Acad. Sci. 83: 6776-6780, 1986.
|
|
|
|
|
|
[PubMed: 3092219]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.83.18.6776]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pannekoek, H., Veerman, H., Lambers, H., Diergaarde, P., Verweij, C. L., van Zonneveld, A.-J., van Mourik, J. A.
|
|
<strong>Endothelial plasminogen activator inhibitor (PAI): a new member of the serpin gene family.</strong>
|
|
EMBO J. 5: 2539-2544, 1986.
|
|
|
|
|
|
[PubMed: 2430793]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1986.tb04532.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pastinen, T., Perola, M., Niini, P., Terwilliger, J., Salomaa, V., Vartiainen, E., Peltonen, L., Syvanen, A.-C.
|
|
<strong>Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population.</strong>
|
|
Hum. Molec. Genet. 7: 1453-1462, 1998.
|
|
|
|
|
|
[PubMed: 9700201]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/7.9.1453]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Patel, N., Tahara, S. M., Malik, P., Kalra, V. K.
|
|
<strong>Involvement of miR-30c and miR-301a in immediate induction of plasminogen activator inhibitor-1 by placental growth factor in human pulmonary endothelial cells.</strong>
|
|
Biochem. J. 434: 473-482, 2011.
|
|
|
|
|
|
[PubMed: 21175428]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1042/BJ20101585]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Patrassi, G. M., Sartori, M. T., Saggiorato, G., Boeri, G., Girolami, A.
|
|
<strong>Familial thrombophila (sic) associated with high levels of plasminogen activator inhibitor.</strong>
|
|
Fibrinolysis 6: 99-103, 1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rossaak, J. I., van Rij, A. M., Jones, G. T., Harris, E. L.
|
|
<strong>Association of the 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor-1 with abdominal aortic aneurysms.</strong>
|
|
J. Vasc. Surg. 31: 1026-1032, 2000.
|
|
|
|
|
|
[PubMed: 10805895]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1067/mva.2000.104589]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sawathiparnich, P., Murphey, L. J., Kumar, S., Vaughan, D. E., Brown, N. J.
|
|
<strong>Effect of combined AT(1) receptor and aldosterone receptor antagonism on plasminogen activator inhibitor-1.</strong>
|
|
J. Clin. Endocr. Metab. 88: 3867-3873, 2003.
|
|
|
|
|
|
[PubMed: 12915681]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2003-030374]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schwartz, C. E., Stanislovitis, P., Phelan, M. C., Klinger, K., Taylor, H. A., Stevenson, R. E.
|
|
<strong>Deletion mapping of plasminogen activator inhibitor, type I (PLANH1) and beta-glucuronidase (GUSB) in 7q21-q22.</strong>
|
|
Cytogenet. Cell Genet. 56: 152-153, 1991.
|
|
|
|
|
|
[PubMed: 2055109]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000133073]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van Zonneveld, A.-J., Curriden, S. A., Loskutoff, D. J.
|
|
<strong>Type 1 plasminogen activator inhibitor gene: functional analysis and glucocorticoid regulation of its promoter.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 5525-5529, 1988.
|
|
|
|
|
|
[PubMed: 2840665]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.85.15.5525]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Westendorp, R. G. J., Hottenga, J.-J., Slagboom, P. E.
|
|
<strong>Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock.</strong>
|
|
Lancet 354: 561-563, 1999.
|
|
|
|
|
|
[PubMed: 10470701]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(98)09376-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamada, N., Arinami, T., Yamakawa-Kobayashi, K., Watanabe, H., Sohda, S., Hamada, H., Kubo, T., Hamaguchi, H.
|
|
<strong>The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia.</strong>
|
|
J. Hum. Genet. 45: 138-141, 2000.
|
|
|
|
|
|
[PubMed: 10807538]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s100380050200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamada, Y., Izawa, H., Ichihara, S., Takatsu, F., Ishihara, H., Hirayama, H., Sone, T., Tanaka, M., Yokota, M.
|
|
<strong>Prediction of the risk of myocardial infarction from polymorphisms in candidate genes.</strong>
|
|
New Eng. J. Med. 347: 1916-1923, 2002.
|
|
|
|
|
|
[PubMed: 12477941]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa021445]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamamoto, K., Takeshita, K., Shimokawa, T., Yi, H., Isobe, K., Loskutoff, D. J., Saito, H.
|
|
<strong>Plasminogen activator inhibitor-1 is a major stress-regulated gene: implications for stress-induced thrombosis in aged individuals.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 890-895, 2002.
|
|
|
|
|
|
[PubMed: 11792849]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.022608799]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yoon, S., Tromp, G., Vongpunsawad, S., Ronkainen, A., Juvonen, T., Kuivaniemi, H.
|
|
<strong>Genetic analysis of MMP3, and PAI-1 in Finnish patients with abdominal aortic or intracranial aneurysms.</strong>
|
|
Biochem. Biophys. Res. Commun. 265: 563-568, 1999.
|
|
|
|
|
|
[PubMed: 10558909]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1999.1721]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, Z. Y., Wang, Z. Y., Dong, N. Z., Bai, X., Zhang, W., Ruan, C. G.
|
|
<strong>A case of deficiency of plasma plasminogen activator inhibitor-1 related to ala15thr mutation in its signal peptide.</strong>
|
|
Blood Coagul. Fibrinolysis. 16: 79-84, 2005.
|
|
|
|
|
|
[PubMed: 15650551]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00001721-200501000-00013]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
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|
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Patricia A. Hartz - updated : 03/18/2014<br>Patricia A. Hartz - updated : 2/29/2012<br>Cassandra L. Kniffin - reorganized : 4/1/2010<br>Cassandra L. Kniffin - updated : 3/30/2010<br>Marla J. F. O'Neill - updated : 3/23/2005<br>John A. Phillips, III - updated : 10/12/2004<br>Victor A. McKusick - updated : 12/17/2002<br>Victor A. McKusick - updated : 2/6/2002<br>Victor A. McKusick - updated : 1/8/2002<br>Victor A. McKusick - updated : 12/14/2001<br>Ada Hamosh - updated : 5/2/2001<br>John A. Phillips, III - updated : 2/9/2001<br>John A. Phillips, III - updated : 10/2/2000<br>Victor A. McKusick - updated : 7/14/2000<br>Victor A. McKusick - updated : 6/12/2000<br>Victor A. McKusick - updated : 11/1/1999<br>Victor A. McKusick - updated : 2/10/1999<br>Victor A. McKusick - updated : 9/17/1998<br>Paul Brennan - updated : 1/16/1998<br>Victor A. McKusick - updated : 9/29/1997
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Victor A. McKusick : 12/15/1986
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alopez : 08/01/2023<br>carol : 08/25/2016<br>carol : 08/24/2016<br>mgross : 03/18/2014<br>carol : 9/17/2013<br>mgross : 3/2/2012<br>terry : 2/29/2012<br>ckniffin : 2/23/2012<br>carol : 4/1/2010<br>carol : 4/1/2010<br>ckniffin : 3/30/2010<br>joanna : 3/19/2010<br>wwang : 8/28/2006<br>carol : 12/13/2005<br>alopez : 12/13/2005<br>alopez : 3/23/2005<br>alopez : 3/23/2005<br>alopez : 10/12/2004<br>tkritzer : 12/20/2002<br>tkritzer : 12/19/2002<br>terry : 12/17/2002<br>ckniffin : 6/5/2002<br>terry : 3/13/2002<br>mgross : 2/11/2002<br>terry : 2/6/2002<br>alopez : 1/8/2002<br>alopez : 1/7/2002<br>terry : 12/14/2001<br>alopez : 5/3/2001<br>terry : 5/2/2001<br>alopez : 2/22/2001<br>terry : 2/9/2001<br>mgross : 10/13/2000<br>terry : 10/2/2000<br>terry : 7/14/2000<br>mcapotos : 6/27/2000<br>terry : 6/12/2000<br>carol : 11/9/1999<br>terry : 11/1/1999<br>terry : 5/5/1999<br>mgross : 3/10/1999<br>carol : 2/17/1999<br>mgross : 2/16/1999<br>mgross : 2/12/1999<br>terry : 2/10/1999<br>carol : 12/13/1998<br>carol : 9/21/1998<br>terry : 9/17/1998<br>carol : 1/16/1998<br>jenny : 10/1/1997<br>terry : 9/29/1997<br>mark : 4/3/1997<br>mimadm : 1/14/1995<br>carol : 7/6/1993<br>carol : 12/8/1992<br>carol : 10/22/1992<br>carol : 10/20/1992<br>carol : 7/2/1992
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