4784 lines
384 KiB
Text
4784 lines
384 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- *147557 - INTEGRIN, BETA-4; ITGB4
|
|
|
|
|
|
- OMIM
|
|
|
|
</title>
|
|
|
|
|
|
|
|
</head>
|
|
|
|
<body>
|
|
<div id="mimBody">
|
|
|
|
|
|
|
|
<div id="mimHeader" class="hidden-print">
|
|
|
|
|
|
|
|
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
|
|
<div class="container-fluid">
|
|
|
|
<!-- Brand and toggle get grouped for better mobile display -->
|
|
<div class="navbar-header">
|
|
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
|
|
<span class="sr-only"> Toggle navigation </span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
</button>
|
|
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
|
|
</div>
|
|
|
|
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
|
|
|
|
<ul class="nav navbar-nav">
|
|
|
|
|
|
<li>
|
|
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
|
|
<li>
|
|
<a href="/statistics/update"> Update List </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/entry"> Entry Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
|
|
|
|
<li>
|
|
<a href="/downloads/"> Register for Downloads </a>
|
|
</li>
|
|
<li>
|
|
<a href="/api"> Register for API Access </a>
|
|
</li>
|
|
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="/contact?mimNumber=147557"><span class="mim-navbar-menu-font"> Contact Us </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li>
|
|
|
|
<a href="/mimmatch/">
|
|
|
|
<span class="mim-navbar-menu-font">
|
|
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
|
|
MIMmatch
|
|
</span>
|
|
</span>
|
|
</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
|
|
<li>
|
|
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
|
|
</li>
|
|
<li>
|
|
<a href="/donors"> Donors </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
|
|
<li>
|
|
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/search"> Search Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/linking"> Linking Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/api"> API Help </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/external"> External Links </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/agreement"> Use Agreement </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/copyright"> Copyright </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimSearch" class="hidden-print">
|
|
|
|
<div class="container">
|
|
|
|
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
|
|
|
|
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
|
|
<input type="hidden" id="mimSearchStart" name="start" value="1" />
|
|
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
|
|
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
|
|
<div class="form-group">
|
|
<div class="input-group">
|
|
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
|
|
<div class="input-group-btn">
|
|
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
|
|
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
|
|
<ul class="dropdown-menu dropdown-menu-right">
|
|
<li class="dropdown-header">
|
|
Advanced Search
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/entry"> OMIM </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/geneMap"> Gene Map </a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/history"> Search History </a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
|
|
<span class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</form>
|
|
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
<!-- <div id="mimSearch"> -->
|
|
|
|
|
|
|
|
|
|
<div id="mimContent">
|
|
|
|
|
|
|
|
<div class="container hidden-print">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
|
|
<div id="mimAlertBanner">
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
|
|
|
|
<div id="mimFloatingTocMenu" class="small" role="navigation">
|
|
|
|
<p>
|
|
<span class="h4">*147557</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#pathogenesis">Pathogenesis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/147557">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<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">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000132470;t=ENST00000200181" 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>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=3691" 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>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=147557" 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>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000132470;t=ENST00000200181" 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>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000213,NM_001005619,NM_001005731,NM_001321123,XM_005257309,XM_005257311,XM_006721866,XM_006721867,XM_006721868,XM_006721870,XM_011524751,XM_011524752,XM_047435926,XM_047435927,XM_047435928,XM_047435929" 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>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000213" 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>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=147557" 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>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://hprd.org/summary?hprd_id=00946&isoform_id=00946_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>
|
|
|
|
|
|
|
|
<div><a href="https://www.proteinatlas.org/search/ITGB4" 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>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/protein/33911,33951,33957,2270923,2270924,2270925,2293521,2293523,6453380,54607027,54607033,54607035,62087406,83318381,111600276,116496731,119609711,119609712,119609713,119609714,119609715,119609716,119609717,119609718,119609719,119609720,119609721,194388316,219517978,219518902,317373584,530412108,530412112,578830851,578830853,578830855,578830859,767994635,767994639,1005880651,2217311584,2217311589,2217311592,2217311594,2462554955,2462554957,2462554959,2462554961,2462554963,2462554965,2462554967,2462554969,2462554971,2462554973,2462554975,2462554977" 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>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.uniprot.org/uniprotkb/P16144" 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>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Gene Info</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="http://biogps.org/#goto=genereport&id=3691" 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>
|
|
|
|
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000132470;t=ENST00000200181" 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>
|
|
|
|
|
|
|
|
<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=ITGB4" 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>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=ITGB4" 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>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+3691" 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>
|
|
|
|
|
|
|
|
<dd><a href="http://v1.marrvel.org/search/gene/ITGB4" 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>
|
|
|
|
|
|
|
|
<dd><a href="https://monarchinitiative.org/NCBIGene:3691" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/3691" 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>
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr17&hgg_gene=ENST00000200181.8&hgg_start=75721459&hgg_end=75757818&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>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/itgb4" 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>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=147557[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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=147557[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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000132470" 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>
|
|
|
|
|
|
|
|
<div><a href="https://www.ebi.ac.uk/gwas/search?query=ITGB4" 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>
|
|
|
|
|
|
|
|
<div><a href="https://www.gwascentral.org/search?q=ITGB4" 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>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ITGB4" 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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ITGB4&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>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.pharmgkb.org/gene/PA29957" 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>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/gene/HGNC:6158" 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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0010395.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>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:96613" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://v1.marrvel.org/search/gene/ITGB4#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>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/marker/MGI:96613" 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>
|
|
|
|
|
|
|
|
|
|
|
|
<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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/3691/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>
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA001948/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=3691" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-030131-7209" 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>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3691" 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>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=ITGB4&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>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<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.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<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">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
147557
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
INTEGRIN, BETA-4; ITGB4
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ITGB4" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ITGB4</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/17/950?start=-3&limit=10&highlight=950">17q25.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:75721459-75757818&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'})">17:75,721,459-75,757,818</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=619816,226730" 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>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/17/950?start=-3&limit=10&highlight=950">
|
|
17q25.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Epidermolysis bullosa, junctional 5A, intermediate
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/619816"> 619816 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Epidermolysis bullosa, junctional 5B, with pyloric atresia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/226730"> 226730 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/147557" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/147557" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#21" class="mim-tip-reference" title="Suzuki, S., Naitoh, Y. <strong>Amino acid sequence of a novel integrin beta-4 subunit and primary expression of the mRNA in epithelial cells.</strong> EMBO J. 9: 757-763, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2311577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2311577</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1990.tb08170.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2311577">Suzuki and Naitoh (1990)</a> isolated a cDNA corresponding to integrin beta-4 (ITGB4). The integrin beta-4 protein contains a putative signal sequence as well as a transmembrane domain that divides the molecule into an extracellular domain at the N-terminal side and a cytoplasmic domain at the C-terminal side. The extracellular domain exhibits a 4-fold repeat of a cysteine-rich motif similar to those of other integrin beta subunits. The cytoplasmic domain is much larger than those of other beta subunits and has no significant homology with them. A protein homology search revealed that the integrin beta-4 cytoplasmic domain has 4 repeating units that are homologous to the type III repetition exhibited by fibronectin. Integrin beta-4 subunit mRNA was expressed primarily in epithelial cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2311577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Hogervorst, F., Kuikman, I., von dem Borne, A. E., Sonnenberg, A. <strong>Cloning and sequence analysis of beta-4 cDNA: an integrin subunit that contains a unique 118 kd cytoplasmic domain.</strong> EMBO J. 9: 765-770, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2311578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2311578</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1990.tb08171.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2311578">Hogervorst et al. (1990)</a> isolated an ITGB4 cDNA. They demonstrated that the ITGB4 extracellular domain shows 35% identify with other integrin beta subunits, but is the most different among this class of molecules. The transmembrane region is poorly conserved, whereas the cytoplasmic domain showed no substantial identity in any region to the cytoplasmic tails of other integrin beta sequences or to other protein sequences. <a href="#8" class="mim-tip-reference" title="Hogervorst, F., Kuikman, I., von dem Borne, A. E., Sonnenberg, A. <strong>Cloning and sequence analysis of beta-4 cDNA: an integrin subunit that contains a unique 118 kd cytoplasmic domain.</strong> EMBO J. 9: 765-770, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2311578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2311578</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1990.tb08171.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2311578">Hogervorst et al. (1990)</a> stated that the exceptionally long cytoplasmic domain suggests distinct interactions of the beta-4 subunit with cytoplasmic proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2311578" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#7" class="mim-tip-reference" title="Hogervorst, F., Kuikman, I., Geurts van Kessel, A., Sonnenberg, A. <strong>Molecular cloning of the human alpha-6 integrin subunit: alternative splicing of alpha-6 mRNA and chromosomal localization of the alpha-6 and beta-4 genes.</strong> Europ. J. Biochem. 199: 425-433, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2070796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2070796</a>] [<a href="https://doi.org/10.1111/j.1432-1033.1991.tb16140.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2070796">Hogervorst et al. (1991)</a> mapped the ITGB4 gene to 17q11-qter by analysis of human-rodent somatic cell hybrids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2070796" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Integrins are transmembrane glycoprotein receptors that mediate cell-matrix or cell-cell adhesion, and transduced signals that regulate gene expression and cell growth (<a href="#22" class="mim-tip-reference" title="Vidal, F., Aberdam, D., Miquel, C., Christiano, A. M., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G. <strong>Integrin beta-4 mutations associated with junctional epidermolysis bullosa with pyloric atresia.</strong> Nature Genet. 10: 229-234, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7545057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7545057</a>] [<a href="https://doi.org/10.1038/ng0695-229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7545057">Vidal et al., 1995</a>). These heterodimeric molecules consist of noncovalently linked alpha and beta subunits. Different combinations of alpha and beta polypeptides form complexes that vary in their ligand-binding specificities. Both alpha and beta subunits display a cytoplasmic domain that interacts with the cytoskeleton (and possibly signaling molecules), a transmembrane region, and a large extracellular domain that interacts with the extracellular matrix. In the human epidermis, basal keratinocytes express integrins alpha-2 (<a href="/entry/192974">192974</a>)/beta-1 (<a href="/entry/135630">135630</a>), alpha-3 (<a href="/entry/605025">605025</a>)/beta-1, and alpha-6 (<a href="/entry/147556">147556</a>)/beta-4. The first 2 of these are located primarily at the lateral surface of these cells, suggesting a role in cell-cell interaction, whereas the third, alpha-6/beta-4, is restricted to the ventral surface opposed to the basal membrane zone, suggestive of its role in cell-matrix adhesion. Consistent with this possibility, alpha-6/beta-4 is found to be associated with the hemidesmosomes in stratified and transitional epithelia. Hemidesmosomes are dense cytoplasmic plaques that mediate the attachment of stratified squamous epithelium to the underlying dermis by connecting with the extracellular anchoring filaments of the basement membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7545057" 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 integrin alpha-6/beta-4, a receptor for the laminins, is likely to play a pivotal role in the biology of invasive carcinoma. In the MDA-MB-435 breast carcinoma cell line, <a href="#20" class="mim-tip-reference" title="Shaw, L. M., Rabinovitz, I., Wang, H. H.-F., Toker, A., Mercurio, A. M. <strong>Activation of phosphoinositide 3-OH kinase by the alpha-6/beta-4 integrin promotes carcinoma invasion.</strong> Cell 91: 949-960, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9428518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9428518</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80486-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9428518">Shaw et al. (1997)</a> demonstrated that the alpha-6/beta-4 integrin promotes carcinoma invasion through a preferential and localized targeting of phosphoinositide-3 OH kinase (PI3K) activity. Stable expression of alpha-6/beta-4 increased carcinoma invasion in a PI3K-dependent manner, and transient expression of a constitutively active PI3K increased invasion in the absence of alpha-6/beta-4. Ligation of alpha-6/beta-4 stimulated significantly more PI3K activity than ligation of beta-1 integrins, establishing specificity among integrins for PI3K activation. Alpha-6/beta-4-regulated PI3K activity was required for the formation of lamellae, dynamic sites of motility, in carcinoma cells. The small G protein Rac is required downstream of PI3K for invasion. <a href="#20" class="mim-tip-reference" title="Shaw, L. M., Rabinovitz, I., Wang, H. H.-F., Toker, A., Mercurio, A. M. <strong>Activation of phosphoinositide 3-OH kinase by the alpha-6/beta-4 integrin promotes carcinoma invasion.</strong> Cell 91: 949-960, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9428518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9428518</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80486-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9428518">Shaw et al. (1997)</a> concluded that their studies defined a mechanism by which the alpha-6/beta-4 integrin promotes carcinoma invasion and invoke a novel function for PI3K signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9428518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Dajee, M., Lazarov, M., Zhang, J. Y., Cai, T., Green, C. L., Russell, A. J., Marinkovich, M. P., Tao, S., Lin, Q., Kubo, Y., Khavari, P. A. <strong>NF-kappa-B blockade and oncogenic Ras trigger invasive human epidermal neoplasia.</strong> Nature 421: 639-643, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12571598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12571598</a>] [<a href="https://doi.org/10.1038/nature01283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12571598">Dajee et al. (2003)</a> showed that human keratinocytes lacking laminin-5 (LAMB3; <a href="/entry/150310">150310</a>) and ITGB4 failed to form tumors on coexpression with RAS (<a href="/entry/190020">190020</a>) and IKBA (NFKBIA; <a href="/entry/164008">164008</a>); however, introduction of wildtype LAMB3 and ITGB4 restored tumor-forming capacity, suggesting that these 2 proteins are required for human squamous cell carcinoma tumorigenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12571598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using expression profiling, <a href="#23" class="mim-tip-reference" title="Yang, L., Zhang, L., Wu, Q., Boyd, D. D. <strong>Unbiased screening for transcriptional targets of ZKSCAN3 identifies integrin beta-4 and vascular endothelial growth factor as downstream targets.</strong> J. Biol. Chem. 283: 35295-35304, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18940803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18940803</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18940803[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/10.1074/jbc.M806965200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18940803">Yang et al. (2008)</a> found that ITGB4 was upregulated 6-fold by ZKSCAN3 (<a href="/entry/612791">612791</a>) in transfected human colon cancer cells compared with parental cells. They confirmed that ZKSCAN3 bound the promoter of ITGB4 in vitro and in vivo. ITGB4 knockdown by short hairpin RNA countered ZKSCAN3-augmented anchorage-independent colony formation in the colon cancer cell lines. <a href="#23" class="mim-tip-reference" title="Yang, L., Zhang, L., Wu, Q., Boyd, D. D. <strong>Unbiased screening for transcriptional targets of ZKSCAN3 identifies integrin beta-4 and vascular endothelial growth factor as downstream targets.</strong> J. Biol. Chem. 283: 35295-35304, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18940803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18940803</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18940803[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/10.1074/jbc.M806965200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18940803">Yang et al. (2008)</a> concluded that ZKSCAN3 regulates expression of genes favoring tumor progression, including ITGB4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18940803" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="pathogenesis" class="mim-anchor"></a>
|
|
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The integrin beta-4 subunit is characterized by an unusually long cytoplasmic domain that harbors 4 fibronectin type III (FNIII) repeats, residing in 2 pairs separated by a connecting segment. A fragment of beta-4 containing the first pair of FNIII repeats and the first 36 amino acids of the connecting segment is crucial for the recruitment of plectin (<a href="/entry/601282">601282</a>) in hemidesmosomes (<a href="#16" class="mim-tip-reference" title="Niessen, C. M., Hulsman, E. H. M., Rots, E. S., Sanchez-Aparicio, P., Sonnenberg, A. <strong>Integrin alpha-6-beta-4 forms a complex with the cytoskeletal protein HD1 and induces its redistribution in transfected COS-7 cells.</strong> Molec. Biol. Cell 8: 555-566, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9247637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9247637</a>] [<a href="https://doi.org/10.1091/mbc.8.4.555" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9247637">Niessen et al., 1997</a>; <a href="#17" class="mim-tip-reference" title="Nievers, M. G., Schaapveld, R. Q. J., Oomen, L. C. J. M., Fontao, L., Geerts, D., Sonnenberg, A. <strong>Ligand-independent role of the beta-4 integrin subunit in the formation of hemidesmosomes.</strong> J. Cell Sci. 111: 1659-1672, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9601096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9601096</a>] [<a href="https://doi.org/10.1242/jcs.111.12.1659" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9601096">Nievers et al., 1998</a>). <a href="#5" class="mim-tip-reference" title="Geerts, D., Fontao, L., Nievers, M. G., Schaapveld, R. Q. J., Purkis, P. E., Wheeler, G. N., Lane, E. B., Leigh, I.M., Sonnenberg, A. <strong>Binding of integrin alpha-6-beta-4 to plectin prevents plectin association with F-actin but does not interfere with intermediate filament binding.</strong> J. Cell Biol. 147: 417-434, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10525545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10525545</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10525545[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1083/jcb.147.2.417" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10525545">Geerts et al. (1999)</a> demonstrated that this fragment of beta-4 contains a binding site for plectin and that this interaction depends in the presence of the actin-binding domain of plectin. Two mutations in ITGB4, arg1281 to trp (R1281W; <a href="#0014">147557.0014</a>) and arg 1225 to his (R1225H; <a href="#0015">147557.0015</a>), are located in the second FNIII repeat; R1281W is localized in the loop region that connects 2 beta strands, whereas R1225H is located in the N-terminal end of the second FNIII repeat. <a href="#11" class="mim-tip-reference" title="Koster, J., Kuikman, I., Kreft, M., Sonnenberg, A. <strong>Two different mutations in the cytoplasmic domain of the integrin 4 subunit in nonlethal forms of epidermolysis bullosa prevent interaction of 4 with plectin.</strong> J. Invest. Derm. 117: 1405-1411, 2001. Note: Erratum: J. Invest. Derm. 118: 910 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11886501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11886501</a>] [<a href="https://doi.org/10.1046/j.0022-202x.2001.01567.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11886501">Koster et al. (2001)</a> demonstrated that these mutations render beta-4 unable to interact with plectin and prevent the localization of plectin in hemidesmosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9601096+10525545+9247637+11886501" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Intermediate Junctional Epidermolysis Bullosa 5A</em></strong></p><p>
|
|
<a href="#9" class="mim-tip-reference" title="Inoue, M., Tamai, K., Shimizu, H., Owaribe, K., Nakama, T., Hashimoto, T., McGrath, J. A. <strong>A homozygous missense mutation in the cytoplasmic tail of beta-4 integrin, G931D, that disrupts hemidesmosome assembly and underlies non-Herlitz junctional epidermolysis bullosa without pyloric atresia?</strong> J. Invest. Derm. 114: 1061-1064, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10792571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10792571</a>] [<a href="https://doi.org/10.1046/j.1523-1747.2000.00960-3.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10792571">Inoue et al. (2000)</a> studied a 68-year-old Japanese man with typical features of non-Herlitz JEB without pyloric atresia (JEB5A; <a href="/entry/618716">618716</a>) who had a homozygous missense mutation in the ITGB4 gene (G931D; <a href="#0012">147557.0012</a>). He had lifelong trauma-induced skin fragility, but no history of gastrointestinal symptoms or previous abdominal surgery. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10792571" 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 49-year-old woman with mild blistering of hands and feet from birth, dystrophy of the nails with onychogryposis, and enamel hypoplasia, without pyloric atresia, <a href="#10" class="mim-tip-reference" title="Jonkman, M. F., Pas, H. H., Nijenhuis, M., Kloosterhuis, G., van der Steege, G. <strong>Deletion of a cytoplasmic domain of integrin beta-4 causes epidermolysis bullosa simplex.</strong> J. Invest. Derm. 119: 1275-1281, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12485428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12485428</a>] [<a href="https://doi.org/10.1046/j.1523-1747.2002.19609.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12485428">Jonkman et al. (2002)</a> identified a heterozygous 2-bp deletion in the ITGB4 gene (<a href="#0013">147557.0013</a>). She was also expected to be heterozygous for a null allele, as no full-size protein was detected in vitro and the epitope 450-11 A was absent in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12485428" 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>Junctional Epidermolysis Bullosa 5B with Pyloric Atresia</em></strong></p><p>
|
|
<a href="#22" class="mim-tip-reference" title="Vidal, F., Aberdam, D., Miquel, C., Christiano, A. M., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G. <strong>Integrin beta-4 mutations associated with junctional epidermolysis bullosa with pyloric atresia.</strong> Nature Genet. 10: 229-234, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7545057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7545057</a>] [<a href="https://doi.org/10.1038/ng0695-229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7545057">Vidal et al. (1995)</a> identified 2 mutations in compound heterozygosity (<a href="#0001">147557.0001</a> and <a href="#0002">147557.0002</a>) in a patient with junctional epidermolysis bullosa associated with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7545057" 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>Improvement with aging has been reported in a few cases of epidermolysis bullosa with pyloric atresia. In a patient who improved from severe to mild JEB-PA, <a href="#3" class="mim-tip-reference" title="Chavanas, S., Gache, Y., Vailly, J., Kanitakis, J., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G. <strong>Splicing modulation of integrin beta-4 pre-mRNA carrying a branch point mutation underlies epidermolysis bullosa with pyloric atresia undergoing spontaneous amelioration with ageing.</strong> Hum. Molec. Genet. 8: 2097-2105, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484780</a>] [<a href="https://doi.org/10.1093/hmg/8.11.2097" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10484780">Chavanas et al. (1999)</a> found compound heterozygosity for 2 splice site mutations in the ITGB4 gene (<a href="#0011">147557.0011</a> and <a href="#0007">147557.0007</a>). Analysis of the mRNA showed that 1 of the mutations prevented legitimate splicing of the beta-4 pre-mRNA. Functional splicing could be restored in vitro by seeding the patient's keratinocytes on feeders of irradiated fibroblasts. Study of mRNA in wildtype keratinocytes transfected with ITGB4 minigenes containing intron 31 with or without the mutation confirmed the causative role in JEB-PA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10484780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Nakano, A., Pulkkinen, L., Murrell, D., Rico, J., Lucky, A. W., Garzon, M., Stevens, C. A., Robertson, S., Pfendner, E., Uitto, J. <strong>Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta-4 integrin gene (ITGB4) and genotype/phenotype correlations.</strong> Pediat. Res. 49: 618-626, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328943</a>] [<a href="https://doi.org/10.1203/00006450-200105000-00003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11328943">Nakano et al. (2001)</a> identified 11 novel mutations in ITGB4 in patients with epidermolysis bullosa with congenital pyloric atresia. Four mutations predicted a premature termination codon and 7 were missense mutations. Of the 33 mutations reported to that time, those causing premature termination codons were associated with the lethal variant, whereas missense mutations were more prevalent in nonlethal forms. In general, indirect immunofluorescent studies of affected skin revealed negative staining for beta-4 integrin in lethal cases and positive, but attenuated, staining in nonlethal cases and correlated with clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11328943" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In addition to promoting cell adhesion and cytoskeletal organization, basement membranes influence the proliferation and differentiation of cells. The effects of basement membranes on cellular behavior are likely to be mediated by integrins. The cytoplasmic domain of the integrin beta-4 subunit mediates both association with the hemidesmosomal cytoskeleton and recruitment of the signaling adaptor protein SHC (<a href="/entry/600560">600560</a>). To examine the significance of these interactions during development, <a href="#14" class="mim-tip-reference" title="Murgia, C., Blaikie, P., Kim, N., Dans, M., Petrie, H. T., Giancotti, F. G. <strong>Cell cycle and adhesion defects in mice carrying a targeted deletion of the integrin beta-4 cytoplasmic domain.</strong> EMBO J. 17: 3940-3951, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9670011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9670011</a>] [<a href="https://doi.org/10.1093/emboj/17.14.3940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9670011">Murgia et al. (1998)</a> generated mice carrying a targeted deletion of the beta-4 cytoplasmic domain. Analysis of homozygous mutant mice indicated that the tail-less alpha-6/beta-4 binds efficiently to laminin-5 (see <a href="/entry/600805">600805</a>), but is unable to integrate with the cytoskeleton. Accordingly, these mice displayed extensive epidermal detachment at birth and died immediately thereafter from a syndrome resembling junctional epidermolysis bullosa with pyloric atresia in humans. In addition, <a href="#14" class="mim-tip-reference" title="Murgia, C., Blaikie, P., Kim, N., Dans, M., Petrie, H. T., Giancotti, F. G. <strong>Cell cycle and adhesion defects in mice carrying a targeted deletion of the integrin beta-4 cytoplasmic domain.</strong> EMBO J. 17: 3940-3951, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9670011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9670011</a>] [<a href="https://doi.org/10.1093/emboj/17.14.3940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9670011">Murgia et al. (1998)</a> found a significant proliferative defect. Specifically, the number of precursor cells in the intestinal epithelium, which remains adherent to the basement membrane, and in intact areas of the skin was reduced, and postmitotic enterocytes displayed increased levels of the cyclin-dependent kinase inhibitor p27(Kip) (<a href="/entry/600778">600778</a>). These findings indicated that the interactions mediated by the beta-4 tail are crucial for stable adhesion of stratified epithelia to the basement membrane and for proper cell cycle control of the proliferative compartments of both stratified and simple epithelia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9670011" 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>Amplification of ERBB2 (<a href="/entry/164870">164870</a>) is common in aggressive breast tumors and correlates with poor prognosis. <a href="#6" class="mim-tip-reference" title="Guo, W., Pylayeva, Y., Pepe, A., Yoshioka, T., Muller, W. J., Inghirami, G., Giancotti, F. G. <strong>Beta-4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis.</strong> Cell 126: 489-502, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16901783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16901783</a>] [<a href="https://doi.org/10.1016/j.cell.2006.05.047" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16901783">Guo et al. (2006)</a> found that deletion of the signaling domain of beta-4 integrin suppressed tumor onset and invasive growth in a mouse model of Erbb2-induced mammary carcinoma. Ex vivo studies showed that beta-4 formed a complex with Erbb2 and enhanced activation of Stat3 (<a href="/entry/102582">102582</a>) and Jun (<a href="/entry/165160">165160</a>). Stat3 contributed to disruption of epithelial adhesion and polarity, whereas Jun was required for hyperproliferation. Deletion of the beta-4 signaling domain enhanced the efficacy of Erbb2-targeted therapy. <a href="#6" class="mim-tip-reference" title="Guo, W., Pylayeva, Y., Pepe, A., Yoshioka, T., Muller, W. J., Inghirami, G., Giancotti, F. G. <strong>Beta-4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis.</strong> Cell 126: 489-502, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16901783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16901783</a>] [<a href="https://doi.org/10.1016/j.cell.2006.05.047" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16901783">Guo et al. (2006)</a> concluded that beta-4 integrin promotes tumor progression by amplifying ERBB2 signaling and is a potential target for breast cancer therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16901783" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>16 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/147557" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=147557[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
|
|
|
|
</div>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0001" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, 1-BP INS, 3801T
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886041205 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886041205;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=rs886041205" 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=rs886041205" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000401703 OR RCV002280814" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000401703, RCV002280814" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000401703...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#22" class="mim-tip-reference" title="Vidal, F., Aberdam, D., Miquel, C., Christiano, A. M., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G. <strong>Integrin beta-4 mutations associated with junctional epidermolysis bullosa with pyloric atresia.</strong> Nature Genet. 10: 229-234, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7545057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7545057</a>] [<a href="https://doi.org/10.1038/ng0695-229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7545057">Vidal et al. (1995)</a> found compound heterozygosity for mutations in the ITGB4 gene in an infant with junctional epidermolysis bullosa associated with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>). The parents were unaffected and unrelated. At birth, the infant presented with pyloric atresia and cutaneous aplasia of the left hand. Perioral blistering and erosions of the mucosa of the mouth, upper esophagus, and cornea were noted shortly after birth. Pyloric atresia was treated surgically at the age of 2 weeks. During a surgical procedure at the age of 8 weeks, erosions of the gastric epithelium were found. At the age of 8 months, infection of skin blisters resulted in generalized infection and death of the infant. In the allele inherited from the mother, an insertion of a T was found after the second base at the 5-prime end of the intron after nucleotide 3801. This was predicted to result in shortening of the cytoplasmic domain of the integrin beta-4 subunit. The mutation was designated 3801+2insT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7545057" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0002" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, 1-BP DEL, 1150G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015851" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015851" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015851</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with JEB associated with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>), <a href="#22" class="mim-tip-reference" title="Vidal, F., Aberdam, D., Miquel, C., Christiano, A. M., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G. <strong>Integrin beta-4 mutations associated with junctional epidermolysis bullosa with pyloric atresia.</strong> Nature Genet. 10: 229-234, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7545057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7545057</a>] [<a href="https://doi.org/10.1038/ng0695-229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7545057">Vidal et al. (1995)</a> found that the mutant allele inherited from the father had deletion of the ITGB4 cDNA sequence. This mutation, 1150delG, resulted in a premature termination codon 168-bp downstream from the deletion, predicting a truncated beta-4 polypeptide terminating at residue 409. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7545057" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0003" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, LEU156PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912461 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912461;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=rs121912461" 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=rs121912461" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015853" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015853" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015853</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mutation in the ITGA6 and ITGB4 genes had been demonstrated in patients with a lethal form of epidermolysis bullosa with congenital pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>). <a href="#18" class="mim-tip-reference" title="Pulkkinen, L., Bruckner-Tuderman, L., August, C., Uitto, J. <strong>Compound heterozygosity for missense mutation (L156P) and nonsense (R554X) mutations in the beta-4 integrin gene (ITGB4) underlies mild, nonlethal phenotype of epidermolysis bullosa with pyloric atresia.</strong> Am. J. Path. 152: 935-941, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9546354/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9546354</a>]" pmid="9546354">Pulkkinen et al. (1998)</a> provided the first demonstration of ITGB4 mutations in nonlethal epidermolysis bullosa with congenital pyloric atresia. The patient was compound heterozygous for a missense mutation (L156P) and a nonsense mutation (R554X; <a href="#0004">147557.0004</a>). The leucine substitution by proline affected a residue conserved in different human, rodent, and Drosophila integrin-beta polypeptides and disrupts the alpha-helix formation of the polypeptide segment. The nonsense mutation was accompanied by undetectable levels of the corresponding mRNA transcript, as determined by RT-PCR. The presence of a missense mutation, when combined with a premature termination codon mutation, may explain the milder blistering tendency of the skin in this patient. The proband was an 18-month-old male, the product of a nonconsanguineous union. Pyloric atresia was diagnosed at birth and treated surgically at the age of 3 days. Following the operation, skin blistering was noted at sites exposed to mechanical trauma, and the blisters healed without apparent scarring, milia, or pigmentary changes. Later on, however, only occasional blisters developed, mostly at the sites of trauma such as the knees and toes, and dystrophy of some toenails developed. The mucous membranes were not involved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9546354" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, ARG554TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<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> rs121912462 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912462;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/rs121912462?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=rs121912462" 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=rs121912462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015854 OR RCV005016271" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015854, RCV005016271" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015854...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg554-to-ter (R554X) mutation in the ITGB4 gene that was found in compound heterozygous state in a patient with lethal epidermolysis bullosa with congenital pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>) by <a href="#18" class="mim-tip-reference" title="Pulkkinen, L., Bruckner-Tuderman, L., August, C., Uitto, J. <strong>Compound heterozygosity for missense mutation (L156P) and nonsense (R554X) mutations in the beta-4 integrin gene (ITGB4) underlies mild, nonlethal phenotype of epidermolysis bullosa with pyloric atresia.</strong> Am. J. Path. 152: 935-941, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9546354/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9546354</a>]" pmid="9546354">Pulkkinen et al. (1998)</a>, see <a href="#0003">147557.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9546354" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0005" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, CYS61TYR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<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> rs80338755 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338755;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/rs80338755?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=rs80338755" 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=rs80338755" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015855 OR RCV000413122 OR RCV002504794 OR RCV003156061" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015855, RCV000413122, RCV002504794, RCV003156061" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015855...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#19" class="mim-tip-reference" title="Pulkkinen, L., Rouan, F., Bruckner-Tuderman, L., Wallerstein, R., Garzon, M., Brown, T., Smith, L., Carter, W., Uitto, J. <strong>Novel ITGB4 mutations in lethal and nonlethal variants of epidermolysis bullosa with pyloric atresia: missense versus nonsense.</strong> Am. J. Hum. Genet. 63: 1376-1387, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792864</a>] [<a href="https://doi.org/10.1086/302116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792864">Pulkkinen et al. (1998)</a> pointed out that patients with the lethal variant of epidermolysis bullosa with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>) usually have mutations leading to premature termination of the protein, whereas missense mutations may lead to nonlethal phenotypes. A missense mutation that resulted in a lethal phenotype involved a cysteine residue (C61Y). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792864" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0006" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, CYS562ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<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> rs121912463 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912463;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/rs121912463?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=rs121912463" 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=rs121912463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015856 OR RCV005089264" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015856, RCV005089264" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015856...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#19" class="mim-tip-reference" title="Pulkkinen, L., Rouan, F., Bruckner-Tuderman, L., Wallerstein, R., Garzon, M., Brown, T., Smith, L., Carter, W., Uitto, J. <strong>Novel ITGB4 mutations in lethal and nonlethal variants of epidermolysis bullosa with pyloric atresia: missense versus nonsense.</strong> Am. J. Hum. Genet. 63: 1376-1387, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792864</a>] [<a href="https://doi.org/10.1086/302116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792864">Pulkkinen et al. (1998)</a> found 1 of 3 patients with a nonlethal form of epidermolysis bullosa with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>) to be homozygous for a cys562-to-arg (C562R) missense mutation in the ITGB4 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792864" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, IVS30DS, G-A, +1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<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> rs147222357 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs147222357;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/rs147222357?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=rs147222357" 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=rs147222357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015857 OR RCV000255841" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015857, RCV000255841" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015857...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#13" class="mim-tip-reference" title="Mellerio, J. E., Pulkkinen, L., McMillan, J. R., Lake, B. D., Horn, H. M., Tidman, M. J., Harper, J. I., McGrath, J. A., Uitto, J., Eady, R. A. J. <strong>Pyloric atresia-junctional epidermolysis bullosa syndrome: mutations in the integrin beta-4 gene (ITGB4) in two unrelated patients with mild disease.</strong> Brit. J. Derm. 139: 862-871, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9892956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9892956</a>] [<a href="https://doi.org/10.1046/j.1365-2133.1998.02515.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9892956">Mellerio et al. (1998)</a> reported 2 unrelated patients with junctional epidermolysis bullosa with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>) who survived into early childhood with mild cutaneous involvement. One patient was compound heterozygous for a splice site mutation in exon 30 (3793+1G-A) and a nonsense mutation in exon 36 (W1478X; <a href="#0008">147557.0008</a>). The second patient was compound heterozygous with a missense mutation in exon 3 (C38R; <a href="#0009">147557.0009</a>) and a 1-bp deletion in exon 36 (4776delG; <a href="#0010">147557.0010</a>). Although the nonsense and deletion mutations were predicted to result in markedly reduced beta-4 integrin mRNA levels, the presence of the missense or splice site mutation on the second allele may enable the synthesis of some functional, albeit perturbed, beta-4 polypeptide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9892956" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, TRP1478TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912464 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912464;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=rs121912464" 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=rs121912464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015858" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015858" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015858</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the trp1478-to-ter (W1478X) mutation in the ITGB4 gene that was found in compound heterozygous state in a patient with junctional epidermolysis bullosa with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>) by <a href="#13" class="mim-tip-reference" title="Mellerio, J. E., Pulkkinen, L., McMillan, J. R., Lake, B. D., Horn, H. M., Tidman, M. J., Harper, J. I., McGrath, J. A., Uitto, J., Eady, R. A. J. <strong>Pyloric atresia-junctional epidermolysis bullosa syndrome: mutations in the integrin beta-4 gene (ITGB4) in two unrelated patients with mild disease.</strong> Brit. J. Derm. 139: 862-871, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9892956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9892956</a>] [<a href="https://doi.org/10.1046/j.1365-2133.1998.02515.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9892956">Mellerio et al. (1998)</a>, see <a href="#0007">147557.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9892956" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, CYS38ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912465 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912465;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=rs121912465" 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=rs121912465" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015859" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015859" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015859</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the cys38-to-arg (C38R) mutation in the ITGB4 gene that was found in compound heterozygous state in a patient with junctional epidermolysis bullosa with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>) by <a href="#13" class="mim-tip-reference" title="Mellerio, J. E., Pulkkinen, L., McMillan, J. R., Lake, B. D., Horn, H. M., Tidman, M. J., Harper, J. I., McGrath, J. A., Uitto, J., Eady, R. A. J. <strong>Pyloric atresia-junctional epidermolysis bullosa syndrome: mutations in the integrin beta-4 gene (ITGB4) in two unrelated patients with mild disease.</strong> Brit. J. Derm. 139: 862-871, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9892956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9892956</a>] [<a href="https://doi.org/10.1046/j.1365-2133.1998.02515.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9892956">Mellerio et al. (1998)</a>, see <a href="#0007">147557.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9892956" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, 1-BP DEL, 4776G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs794726676 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs794726676;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=rs794726676" 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=rs794726676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015852 OR RCV005025059" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015852, RCV005025059" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015852...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion in the ITGB4 gene (4776delG) that was found in compound heterozygous state in a patient with junctional epidermolysis bullosa with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>) by <a href="#13" class="mim-tip-reference" title="Mellerio, J. E., Pulkkinen, L., McMillan, J. R., Lake, B. D., Horn, H. M., Tidman, M. J., Harper, J. I., McGrath, J. A., Uitto, J., Eady, R. A. J. <strong>Pyloric atresia-junctional epidermolysis bullosa syndrome: mutations in the integrin beta-4 gene (ITGB4) in two unrelated patients with mild disease.</strong> Brit. J. Derm. 139: 862-871, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9892956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9892956</a>] [<a href="https://doi.org/10.1046/j.1365-2133.1998.02515.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9892956">Mellerio et al. (1998)</a>, see <a href="#0007">147557.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9892956" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, IVS31DS, T-A, -19
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<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> rs1434530468 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1434530468;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/rs1434530468?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=rs1434530468" 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=rs1434530468" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015860 OR RCV003556028" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015860, RCV003556028" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015860...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#3" class="mim-tip-reference" title="Chavanas, S., Gache, Y., Vailly, J., Kanitakis, J., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G. <strong>Splicing modulation of integrin beta-4 pre-mRNA carrying a branch point mutation underlies epidermolysis bullosa with pyloric atresia undergoing spontaneous amelioration with ageing.</strong> Hum. Molec. Genet. 8: 2097-2105, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484780</a>] [<a href="https://doi.org/10.1093/hmg/8.11.2097" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10484780">Chavanas et al. (1999)</a> reported a patient who represented the rare instance in which epidermolysis bullosa with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>) shows improvement with age. The proband was a 14-year-old boy, the child of nonconsanguineous parents, who at birth presented all the hallmarks of severe PA-JEB, including extensive skin blistering, pyloric atresia, and urethrovesical occlusion. As the child grew, however, the blistering tendency decreased and his skin and epithelia acquired resistance to trauma. At the age of 14, induction of blisters required prolonged rubbing of the skin. In this patient, <a href="#3" class="mim-tip-reference" title="Chavanas, S., Gache, Y., Vailly, J., Kanitakis, J., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G. <strong>Splicing modulation of integrin beta-4 pre-mRNA carrying a branch point mutation underlies epidermolysis bullosa with pyloric atresia undergoing spontaneous amelioration with ageing.</strong> Hum. Molec. Genet. 8: 2097-2105, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484780</a>] [<a href="https://doi.org/10.1093/hmg/8.11.2097" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10484780">Chavanas et al. (1999)</a> found compound heterozygosity for the intron 30 splice donor site mutation (3802+1G-A; <a href="#0007">147557.0007</a>) and a novel T-to-A transversion at nucleotide 3986-19 in intron 31 of the ITGB4 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10484780" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5A, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, GLY931ASP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912466 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912466;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=rs121912466" 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=rs121912466" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV002051629" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002051629" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002051629</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 68-year-old male with typical non-Herlitz junctional epidermolysis bullosa (JEB5A; <a href="/entry/619816">619816</a>) without pyloric atresia, <a href="#9" class="mim-tip-reference" title="Inoue, M., Tamai, K., Shimizu, H., Owaribe, K., Nakama, T., Hashimoto, T., McGrath, J. A. <strong>A homozygous missense mutation in the cytoplasmic tail of beta-4 integrin, G931D, that disrupts hemidesmosome assembly and underlies non-Herlitz junctional epidermolysis bullosa without pyloric atresia?</strong> J. Invest. Derm. 114: 1061-1064, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10792571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10792571</a>] [<a href="https://doi.org/10.1046/j.1523-1747.2000.00960-3.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10792571">Inoue et al. (2000)</a> reported a homozygous ITGB4 gly931-to-asp (G931D) mutation. The patient, who was the product of a consanguineous mating, had a history of congenital blisters, recurrent urethral stenosis since age 12 years, progressive alopecia since childhood, loss of permanent dentition by age 30 years, nail dystrophy, and absence of pubic and axillary hair. There was no history of gastrointestinal symptoms or previous abdominal surgery. The mutation, a G-to-A transition at nucleotide 2792, created a novel BsmF1 cut site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10792571" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5A, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, 2-BP DEL, 4733CT
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV002051630" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002051630" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002051630</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#10" class="mim-tip-reference" title="Jonkman, M. F., Pas, H. H., Nijenhuis, M., Kloosterhuis, G., van der Steege, G. <strong>Deletion of a cytoplasmic domain of integrin beta-4 causes epidermolysis bullosa simplex.</strong> J. Invest. Derm. 119: 1275-1281, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12485428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12485428</a>] [<a href="https://doi.org/10.1046/j.1523-1747.2002.19609.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12485428">Jonkman et al. (2002)</a> reported a patient with predominant features of epidermolysis bullosa simplex confined to the hands and feet (JEB5A; <a href="/entry/619816">619816</a>) due to a heterozygous 2-bp deletion (4733delCT) in the ITGB4 gene, resulting in in-frame skipping of exon 36 and a deduced 50-amino acid deletion (1450-1499) within the third fibronectin type III repeat in the cytoplasmic domain of integrin beta-4. Although mutation in exon 36 of the ITGB4 gene had been reported in epidermolysis bullosa with pyloric atresia (<a href="/entry/226730">226730</a>) (see <a href="#0007">147557.0007</a>), this patient had no history of pyloric atresia. The patient, a 49-year-old female, had mild blistering of hands and feet from birth, dystrophy of the nails with onychogryposis, and enamel hypoplasia. Electron microscopy and antigen mapping of a skin blister revealed that the level of separation was intraepidermal, low in the basal keratinocytes through the attachment plaque of the hemidesmosome. Immunofluorescence microscopy revealed absent binding of monoclonal antibody 450-11 A against the third fibronectin III repeat on the intracellular domain of integrin beta-4, whereas binding was reduced with monoclonal antibodies recognizing epitopes on amino-terminal and carboxy-terminal ends of the polypeptide. Immunoblot analysis demonstrated a 5-kD shorter beta-4 polypeptide. The patient was also expected to be heterozygous for a null allele, as no full-size protein was detected in vitro and the epitope 450-11 A was absent in vivo. These data showed that deletion of the third fibronectin type III repeat in the cytoplasmic domain of integrin beta-4, which is thought to interact with BP180/type XVII collagen (<a href="/entry/113811">113811</a>), is clinically pathogenic and results in a mild phenotype. Although <a href="#10" class="mim-tip-reference" title="Jonkman, M. F., Pas, H. H., Nijenhuis, M., Kloosterhuis, G., van der Steege, G. <strong>Deletion of a cytoplasmic domain of integrin beta-4 causes epidermolysis bullosa simplex.</strong> J. Invest. Derm. 119: 1275-1281, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12485428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12485428</a>] [<a href="https://doi.org/10.1046/j.1523-1747.2002.19609.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12485428">Jonkman et al. (2002)</a> stated that the level of skin separation was intraepidermal (i.e., consistent with that seen in epidermolysis bullosa simplex), they pointed out that 'pseudojunctional' splits very low in the basal cells had been reported in patients with JEB with pyloric atresia carrying mutations in the ITGB4 gene (e.g., <a href="#18" class="mim-tip-reference" title="Pulkkinen, L., Bruckner-Tuderman, L., August, C., Uitto, J. <strong>Compound heterozygosity for missense mutation (L156P) and nonsense (R554X) mutations in the beta-4 integrin gene (ITGB4) underlies mild, nonlethal phenotype of epidermolysis bullosa with pyloric atresia.</strong> Am. J. Path. 152: 935-941, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9546354/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9546354</a>]" pmid="9546354">Pulkkinen et al. (1998)</a>, <a href="#13" class="mim-tip-reference" title="Mellerio, J. E., Pulkkinen, L., McMillan, J. R., Lake, B. D., Horn, H. M., Tidman, M. J., Harper, J. I., McGrath, J. A., Uitto, J., Eady, R. A. J. <strong>Pyloric atresia-junctional epidermolysis bullosa syndrome: mutations in the integrin beta-4 gene (ITGB4) in two unrelated patients with mild disease.</strong> Brit. J. Derm. 139: 862-871, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9892956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9892956</a>] [<a href="https://doi.org/10.1046/j.1365-2133.1998.02515.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9892956">Mellerio et al. (1998)</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9546354+12485428+9892956" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0014" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, ARG1281TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<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> rs121912467 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912467;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/rs121912467?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=rs121912467" 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=rs121912467" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015863 OR RCV000359496 OR RCV004586010 OR RCV005016272" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015863, RCV000359496, RCV004586010, RCV005016272" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015863...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with epidermolysis bullosa with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>), <a href="#19" class="mim-tip-reference" title="Pulkkinen, L., Rouan, F., Bruckner-Tuderman, L., Wallerstein, R., Garzon, M., Brown, T., Smith, L., Carter, W., Uitto, J. <strong>Novel ITGB4 mutations in lethal and nonlethal variants of epidermolysis bullosa with pyloric atresia: missense versus nonsense.</strong> Am. J. Hum. Genet. 63: 1376-1387, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792864</a>] [<a href="https://doi.org/10.1086/302116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9792864">Pulkkinen et al. (1998)</a> described an arg1281-to-trp (R1281W) mutation in the ITGB4 gene. In 1 patient the mutation was homozygous, and in the other compound heterozygous with another missense mutation. <a href="#11" class="mim-tip-reference" title="Koster, J., Kuikman, I., Kreft, M., Sonnenberg, A. <strong>Two different mutations in the cytoplasmic domain of the integrin 4 subunit in nonlethal forms of epidermolysis bullosa prevent interaction of 4 with plectin.</strong> J. Invest. Derm. 117: 1405-1411, 2001. Note: Erratum: J. Invest. Derm. 118: 910 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11886501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11886501</a>] [<a href="https://doi.org/10.1046/j.0022-202x.2001.01567.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11886501">Koster et al. (2001)</a> reported that this mutation renders integrin beta-4 unable to interact with plectin (<a href="/entry/601282">601282</a>) and prevents the localization of plectin in hemidesmosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9792864+11886501" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0015" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, ARG1225HIS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<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> rs121912468 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912468;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/rs121912468?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=rs121912468" 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=rs121912468" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015864" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015864" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015864</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an individual with epidermolysis bullosa with pyloric atresia (JEB5B; <a href="/entry/226730">226730</a>), <a href="#15" class="mim-tip-reference" title="Nakano, A., Pulkkinen, L., Murrell, D., Rico, J., Lucky, A. W., Garzon, M., Stevens, C. A., Robertson, S., Pfendner, E., Uitto, J. <strong>Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta-4 integrin gene (ITGB4) and genotype/phenotype correlations.</strong> Pediat. Res. 49: 618-626, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328943</a>] [<a href="https://doi.org/10.1203/00006450-200105000-00003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11328943">Nakano et al. (2001)</a> found an arg1225-to-his (R1225H) mutation in the ITGB4 gene. The mutation occurred in compound heterozygosity. The blistering tendency of the patient improved with time. <a href="#11" class="mim-tip-reference" title="Koster, J., Kuikman, I., Kreft, M., Sonnenberg, A. <strong>Two different mutations in the cytoplasmic domain of the integrin 4 subunit in nonlethal forms of epidermolysis bullosa prevent interaction of 4 with plectin.</strong> J. Invest. Derm. 117: 1405-1411, 2001. Note: Erratum: J. Invest. Derm. 118: 910 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11886501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11886501</a>] [<a href="https://doi.org/10.1046/j.0022-202x.2001.01567.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11886501">Koster et al. (2001)</a> reported that this mutation renders integrin beta-4 unable to interact with plectin (<a href="/entry/601282">601282</a>) and prevents the localization of plectin in hemidesmosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11886501+11328943" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0016" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ITGB4, 2,279-BP DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015865" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015865" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015865</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of the original Bedouin kindred from southern Israel with epidermolysis bullosa with pyloric atresia and aplasia cutis congenita (JEB5B; <a href="/entry/226730">226730</a>), described by <a href="#2" class="mim-tip-reference" title="Carmi, R., Sofer, S., Karplus, M., Ben-Yakar, Y., Mahler, D., Zirkin, H., Bar-Ziv, J. <strong>Aplasia cutis congenita in two sibs discordant for pyloric atresia.</strong> Am. J. Med. Genet. 11: 319-328, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6177243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6177243</a>] [<a href="https://doi.org/10.1002/ajmg.1320110308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6177243">Carmi et al. (1982)</a> and <a href="#12" class="mim-tip-reference" title="Maman, E., Maor, E., Kachko, L., Carmi, R. <strong>Epidermolysis bullosa, pyloric atresia, aplasia cutis congenita: histopathological delineation of an autosomal recessive disease.</strong> Am. J. Med. Genet. 78: 127-133, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9674902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9674902</a>]" pmid="9674902">Maman et al. (1998)</a>, <a href="#1" class="mim-tip-reference" title="Birnbaum, R. Y., Landau, D., Elbedour, K., Ofir, R., Birk, O. S., Carmi, R. <strong>Deletion of the first pair of fibronectin type III repeats of the integrin beta-4 gene is associated with epidermolysis bullosa, pyloric atresia and aplasia cutis congenita in the original Carmi syndrome patients. (Letter)</strong> Am. J. Med. Genet. 146A: 1063-1066, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348258</a>] [<a href="https://doi.org/10.1002/ajmg.a.31903" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18348258">Birnbaum et al. (2008)</a> identified a homozygous 2,279-bp in-frame deletion in part of exon 27 and all of exons 28-30 of the ITGB4 gene in 3 affected family members. The deletion includes the authentic 5-prime splice site of exon 27 that creates a new cryptic 5-prime splice site leading to a 570-bp deletion within the integrin beta-4 final transcript. The mutation generates an in-frame deletion of 190 amino acids (1075-1266). The ITGB4 fragment deleted in this family encodes the first pair of fibronectin type III (FNIII) repeats. <a href="#1" class="mim-tip-reference" title="Birnbaum, R. Y., Landau, D., Elbedour, K., Ofir, R., Birk, O. S., Carmi, R. <strong>Deletion of the first pair of fibronectin type III repeats of the integrin beta-4 gene is associated with epidermolysis bullosa, pyloric atresia and aplasia cutis congenita in the original Carmi syndrome patients. (Letter)</strong> Am. J. Med. Genet. 146A: 1063-1066, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348258</a>] [<a href="https://doi.org/10.1002/ajmg.a.31903" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18348258">Birnbaum et al. (2008)</a> suggested that the deletion affected the integrity of the basement membrane and the assembly of hemidesmosomes, consequently abrogating the control of normal skin structure. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6177243+9674902+18348258" 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>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Birnbaum2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Birnbaum, R. Y., Landau, D., Elbedour, K., Ofir, R., Birk, O. S., Carmi, R.
|
|
<strong>Deletion of the first pair of fibronectin type III repeats of the integrin beta-4 gene is associated with epidermolysis bullosa, pyloric atresia and aplasia cutis congenita in the original Carmi syndrome patients. (Letter)</strong>
|
|
Am. J. Med. Genet. 146A: 1063-1066, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348258</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18348258" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.31903" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Carmi1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Carmi, R., Sofer, S., Karplus, M., Ben-Yakar, Y., Mahler, D., Zirkin, H., Bar-Ziv, J.
|
|
<strong>Aplasia cutis congenita in two sibs discordant for pyloric atresia.</strong>
|
|
Am. J. Med. Genet. 11: 319-328, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6177243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6177243</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6177243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320110308" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Chavanas1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chavanas, S., Gache, Y., Vailly, J., Kanitakis, J., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G.
|
|
<strong>Splicing modulation of integrin beta-4 pre-mRNA carrying a branch point mutation underlies epidermolysis bullosa with pyloric atresia undergoing spontaneous amelioration with ageing.</strong>
|
|
Hum. Molec. Genet. 8: 2097-2105, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484780</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10484780" 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/8.11.2097" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Dajee2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dajee, M., Lazarov, M., Zhang, J. Y., Cai, T., Green, C. L., Russell, A. J., Marinkovich, M. P., Tao, S., Lin, Q., Kubo, Y., Khavari, P. A.
|
|
<strong>NF-kappa-B blockade and oncogenic Ras trigger invasive human epidermal neoplasia.</strong>
|
|
Nature 421: 639-643, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12571598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12571598</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12571598" 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/nature01283" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Geerts1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Geerts, D., Fontao, L., Nievers, M. G., Schaapveld, R. Q. J., Purkis, P. E., Wheeler, G. N., Lane, E. B., Leigh, I.M., Sonnenberg, A.
|
|
<strong>Binding of integrin alpha-6-beta-4 to plectin prevents plectin association with F-actin but does not interfere with intermediate filament binding.</strong>
|
|
J. Cell Biol. 147: 417-434, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10525545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10525545</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10525545[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=10525545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1083/jcb.147.2.417" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Guo2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guo, W., Pylayeva, Y., Pepe, A., Yoshioka, T., Muller, W. J., Inghirami, G., Giancotti, F. G.
|
|
<strong>Beta-4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis.</strong>
|
|
Cell 126: 489-502, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16901783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16901783</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16901783" 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/j.cell.2006.05.047" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Hogervorst1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hogervorst, F., Kuikman, I., Geurts van Kessel, A., Sonnenberg, A.
|
|
<strong>Molecular cloning of the human alpha-6 integrin subunit: alternative splicing of alpha-6 mRNA and chromosomal localization of the alpha-6 and beta-4 genes.</strong>
|
|
Europ. J. Biochem. 199: 425-433, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2070796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2070796</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2070796" 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.1432-1033.1991.tb16140.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Hogervorst1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hogervorst, F., Kuikman, I., von dem Borne, A. E., Sonnenberg, A.
|
|
<strong>Cloning and sequence analysis of beta-4 cDNA: an integrin subunit that contains a unique 118 kd cytoplasmic domain.</strong>
|
|
EMBO J. 9: 765-770, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2311578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2311578</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2311578" 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.1460-2075.1990.tb08171.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Inoue2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Inoue, M., Tamai, K., Shimizu, H., Owaribe, K., Nakama, T., Hashimoto, T., McGrath, J. A.
|
|
<strong>A homozygous missense mutation in the cytoplasmic tail of beta-4 integrin, G931D, that disrupts hemidesmosome assembly and underlies non-Herlitz junctional epidermolysis bullosa without pyloric atresia?</strong>
|
|
J. Invest. Derm. 114: 1061-1064, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10792571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10792571</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10792571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1523-1747.2000.00960-3.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Jonkman2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jonkman, M. F., Pas, H. H., Nijenhuis, M., Kloosterhuis, G., van der Steege, G.
|
|
<strong>Deletion of a cytoplasmic domain of integrin beta-4 causes epidermolysis bullosa simplex.</strong>
|
|
J. Invest. Derm. 119: 1275-1281, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12485428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12485428</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12485428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1523-1747.2002.19609.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Koster2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koster, J., Kuikman, I., Kreft, M., Sonnenberg, A.
|
|
<strong>Two different mutations in the cytoplasmic domain of the integrin 4 subunit in nonlethal forms of epidermolysis bullosa prevent interaction of 4 with plectin.</strong>
|
|
J. Invest. Derm. 117: 1405-1411, 2001. Note: Erratum: J. Invest. Derm. 118: 910 only, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11886501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11886501</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11886501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.0022-202x.2001.01567.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Maman1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maman, E., Maor, E., Kachko, L., Carmi, R.
|
|
<strong>Epidermolysis bullosa, pyloric atresia, aplasia cutis congenita: histopathological delineation of an autosomal recessive disease.</strong>
|
|
Am. J. Med. Genet. 78: 127-133, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9674902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9674902</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9674902" 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="Mellerio1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mellerio, J. E., Pulkkinen, L., McMillan, J. R., Lake, B. D., Horn, H. M., Tidman, M. J., Harper, J. I., McGrath, J. A., Uitto, J., Eady, R. A. J.
|
|
<strong>Pyloric atresia-junctional epidermolysis bullosa syndrome: mutations in the integrin beta-4 gene (ITGB4) in two unrelated patients with mild disease.</strong>
|
|
Brit. J. Derm. 139: 862-871, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9892956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9892956</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9892956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2133.1998.02515.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Murgia1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Murgia, C., Blaikie, P., Kim, N., Dans, M., Petrie, H. T., Giancotti, F. G.
|
|
<strong>Cell cycle and adhesion defects in mice carrying a targeted deletion of the integrin beta-4 cytoplasmic domain.</strong>
|
|
EMBO J. 17: 3940-3951, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9670011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9670011</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9670011" 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/emboj/17.14.3940" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Nakano2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nakano, A., Pulkkinen, L., Murrell, D., Rico, J., Lucky, A. W., Garzon, M., Stevens, C. A., Robertson, S., Pfendner, E., Uitto, J.
|
|
<strong>Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta-4 integrin gene (ITGB4) and genotype/phenotype correlations.</strong>
|
|
Pediat. Res. 49: 618-626, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11328943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11328943</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11328943" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1203/00006450-200105000-00003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Niessen1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Niessen, C. M., Hulsman, E. H. M., Rots, E. S., Sanchez-Aparicio, P., Sonnenberg, A.
|
|
<strong>Integrin alpha-6-beta-4 forms a complex with the cytoskeletal protein HD1 and induces its redistribution in transfected COS-7 cells.</strong>
|
|
Molec. Biol. Cell 8: 555-566, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9247637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9247637</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9247637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1091/mbc.8.4.555" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Nievers1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nievers, M. G., Schaapveld, R. Q. J., Oomen, L. C. J. M., Fontao, L., Geerts, D., Sonnenberg, A.
|
|
<strong>Ligand-independent role of the beta-4 integrin subunit in the formation of hemidesmosomes.</strong>
|
|
J. Cell Sci. 111: 1659-1672, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9601096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9601096</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9601096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1242/jcs.111.12.1659" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Pulkkinen1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pulkkinen, L., Bruckner-Tuderman, L., August, C., Uitto, J.
|
|
<strong>Compound heterozygosity for missense mutation (L156P) and nonsense (R554X) mutations in the beta-4 integrin gene (ITGB4) underlies mild, nonlethal phenotype of epidermolysis bullosa with pyloric atresia.</strong>
|
|
Am. J. Path. 152: 935-941, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9546354/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9546354</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9546354" 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="19" class="mim-anchor"></a>
|
|
<a id="Pulkkinen1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pulkkinen, L., Rouan, F., Bruckner-Tuderman, L., Wallerstein, R., Garzon, M., Brown, T., Smith, L., Carter, W., Uitto, J.
|
|
<strong>Novel ITGB4 mutations in lethal and nonlethal variants of epidermolysis bullosa with pyloric atresia: missense versus nonsense.</strong>
|
|
Am. J. Hum. Genet. 63: 1376-1387, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792864</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792864" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302116" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Shaw1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shaw, L. M., Rabinovitz, I., Wang, H. H.-F., Toker, A., Mercurio, A. M.
|
|
<strong>Activation of phosphoinositide 3-OH kinase by the alpha-6/beta-4 integrin promotes carcinoma invasion.</strong>
|
|
Cell 91: 949-960, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9428518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9428518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9428518" 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/s0092-8674(00)80486-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Suzuki1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Suzuki, S., Naitoh, Y.
|
|
<strong>Amino acid sequence of a novel integrin beta-4 subunit and primary expression of the mRNA in epithelial cells.</strong>
|
|
EMBO J. 9: 757-763, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2311577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2311577</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2311577" 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.1460-2075.1990.tb08170.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Vidal1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vidal, F., Aberdam, D., Miquel, C., Christiano, A. M., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G.
|
|
<strong>Integrin beta-4 mutations associated with junctional epidermolysis bullosa with pyloric atresia.</strong>
|
|
Nature Genet. 10: 229-234, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7545057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7545057</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7545057" 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/ng0695-229" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Yang2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yang, L., Zhang, L., Wu, Q., Boyd, D. D.
|
|
<strong>Unbiased screening for transcriptional targets of ZKSCAN3 identifies integrin beta-4 and vascular endothelial growth factor as downstream targets.</strong>
|
|
J. Biol. Chem. 283: 35295-35304, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18940803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18940803</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18940803[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=18940803" 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.M806965200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Patricia A. Hartz - updated : 5/19/2009
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Kelly A. Przylepa - updated : 2/5/2009<br>Matthew B. Gross - updated : 2/8/2007<br>Anne M. Stumpf - reorganized : 5/21/2003<br>Gary A. Bellus - updated : 5/21/2003<br>Gary A. Bellus - updated : 5/13/2003<br>Ada Hamosh - updated : 2/13/2002<br>Gary A. Bellus - updated : 6/12/2000<br>Victor A. McKusick - updated : 10/25/1999<br>Victor A. McKusick - updated : 2/1/1999<br>Victor A. McKusick - updated : 12/8/1998<br>Victor A. McKusick - updated : 10/7/1998<br>Victor A. McKusick - updated : 7/2/1998<br>Stylianos E. Antonarakis - updated : 2/20/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 3/3/1992
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 03/29/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
mcolton : 06/15/2015<br>terry : 4/1/2013<br>terry : 6/11/2012<br>mgross : 5/19/2009<br>carol : 2/5/2009<br>terry : 2/5/2009<br>carol : 7/9/2008<br>ckniffin : 7/2/2008<br>ckniffin : 5/29/2008<br>ckniffin : 5/23/2008<br>wwang : 2/22/2007<br>mgross : 2/8/2007<br>wwang : 12/20/2006<br>cwells : 11/10/2003<br>cwells : 11/10/2003<br>alopez : 5/21/2003<br>alopez : 5/21/2003<br>carol : 5/14/2003<br>alopez : 5/13/2003<br>alopez : 2/13/2002<br>terry : 2/13/2002<br>terry : 6/7/2001<br>alopez : 6/12/2000<br>alopez : 6/12/2000<br>mgross : 11/5/1999<br>terry : 10/25/1999<br>carol : 2/3/1999<br>terry : 2/1/1999<br>carol : 12/11/1998<br>terry : 12/8/1998<br>carol : 10/14/1998<br>terry : 10/7/1998<br>terry : 8/24/1998<br>carol : 7/13/1998<br>terry : 7/2/1998<br>dholmes : 2/20/1998<br>dholmes : 2/20/1998<br>dholmes : 2/19/1998<br>terry : 7/1/1996<br>terry : 7/1/1996<br>mark : 6/1/1995<br>supermim : 3/16/1992<br>carol : 3/3/1992
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 147557
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
INTEGRIN, BETA-4; ITGB4
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: ITGB4</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 17q25.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 17:75,721,459-75,757,818 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
17q25.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Epidermolysis bullosa, junctional 5A, intermediate
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
619816
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Epidermolysis bullosa, junctional 5B, with pyloric atresia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
226730
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Suzuki and Naitoh (1990) isolated a cDNA corresponding to integrin beta-4 (ITGB4). The integrin beta-4 protein contains a putative signal sequence as well as a transmembrane domain that divides the molecule into an extracellular domain at the N-terminal side and a cytoplasmic domain at the C-terminal side. The extracellular domain exhibits a 4-fold repeat of a cysteine-rich motif similar to those of other integrin beta subunits. The cytoplasmic domain is much larger than those of other beta subunits and has no significant homology with them. A protein homology search revealed that the integrin beta-4 cytoplasmic domain has 4 repeating units that are homologous to the type III repetition exhibited by fibronectin. Integrin beta-4 subunit mRNA was expressed primarily in epithelial cells. </p><p>Hogervorst et al. (1990) isolated an ITGB4 cDNA. They demonstrated that the ITGB4 extracellular domain shows 35% identify with other integrin beta subunits, but is the most different among this class of molecules. The transmembrane region is poorly conserved, whereas the cytoplasmic domain showed no substantial identity in any region to the cytoplasmic tails of other integrin beta sequences or to other protein sequences. Hogervorst et al. (1990) stated that the exceptionally long cytoplasmic domain suggests distinct interactions of the beta-4 subunit with cytoplasmic proteins. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Hogervorst et al. (1991) mapped the ITGB4 gene to 17q11-qter by analysis of human-rodent somatic cell hybrids. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Integrins are transmembrane glycoprotein receptors that mediate cell-matrix or cell-cell adhesion, and transduced signals that regulate gene expression and cell growth (Vidal et al., 1995). These heterodimeric molecules consist of noncovalently linked alpha and beta subunits. Different combinations of alpha and beta polypeptides form complexes that vary in their ligand-binding specificities. Both alpha and beta subunits display a cytoplasmic domain that interacts with the cytoskeleton (and possibly signaling molecules), a transmembrane region, and a large extracellular domain that interacts with the extracellular matrix. In the human epidermis, basal keratinocytes express integrins alpha-2 (192974)/beta-1 (135630), alpha-3 (605025)/beta-1, and alpha-6 (147556)/beta-4. The first 2 of these are located primarily at the lateral surface of these cells, suggesting a role in cell-cell interaction, whereas the third, alpha-6/beta-4, is restricted to the ventral surface opposed to the basal membrane zone, suggestive of its role in cell-matrix adhesion. Consistent with this possibility, alpha-6/beta-4 is found to be associated with the hemidesmosomes in stratified and transitional epithelia. Hemidesmosomes are dense cytoplasmic plaques that mediate the attachment of stratified squamous epithelium to the underlying dermis by connecting with the extracellular anchoring filaments of the basement membrane. </p><p>The integrin alpha-6/beta-4, a receptor for the laminins, is likely to play a pivotal role in the biology of invasive carcinoma. In the MDA-MB-435 breast carcinoma cell line, Shaw et al. (1997) demonstrated that the alpha-6/beta-4 integrin promotes carcinoma invasion through a preferential and localized targeting of phosphoinositide-3 OH kinase (PI3K) activity. Stable expression of alpha-6/beta-4 increased carcinoma invasion in a PI3K-dependent manner, and transient expression of a constitutively active PI3K increased invasion in the absence of alpha-6/beta-4. Ligation of alpha-6/beta-4 stimulated significantly more PI3K activity than ligation of beta-1 integrins, establishing specificity among integrins for PI3K activation. Alpha-6/beta-4-regulated PI3K activity was required for the formation of lamellae, dynamic sites of motility, in carcinoma cells. The small G protein Rac is required downstream of PI3K for invasion. Shaw et al. (1997) concluded that their studies defined a mechanism by which the alpha-6/beta-4 integrin promotes carcinoma invasion and invoke a novel function for PI3K signaling. </p><p>Dajee et al. (2003) showed that human keratinocytes lacking laminin-5 (LAMB3; 150310) and ITGB4 failed to form tumors on coexpression with RAS (190020) and IKBA (NFKBIA; 164008); however, introduction of wildtype LAMB3 and ITGB4 restored tumor-forming capacity, suggesting that these 2 proteins are required for human squamous cell carcinoma tumorigenesis. </p><p>Using expression profiling, Yang et al. (2008) found that ITGB4 was upregulated 6-fold by ZKSCAN3 (612791) in transfected human colon cancer cells compared with parental cells. They confirmed that ZKSCAN3 bound the promoter of ITGB4 in vitro and in vivo. ITGB4 knockdown by short hairpin RNA countered ZKSCAN3-augmented anchorage-independent colony formation in the colon cancer cell lines. Yang et al. (2008) concluded that ZKSCAN3 regulates expression of genes favoring tumor progression, including ITGB4. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The integrin beta-4 subunit is characterized by an unusually long cytoplasmic domain that harbors 4 fibronectin type III (FNIII) repeats, residing in 2 pairs separated by a connecting segment. A fragment of beta-4 containing the first pair of FNIII repeats and the first 36 amino acids of the connecting segment is crucial for the recruitment of plectin (601282) in hemidesmosomes (Niessen et al., 1997; Nievers et al., 1998). Geerts et al. (1999) demonstrated that this fragment of beta-4 contains a binding site for plectin and that this interaction depends in the presence of the actin-binding domain of plectin. Two mutations in ITGB4, arg1281 to trp (R1281W; 147557.0014) and arg 1225 to his (R1225H; 147557.0015), are located in the second FNIII repeat; R1281W is localized in the loop region that connects 2 beta strands, whereas R1225H is located in the N-terminal end of the second FNIII repeat. Koster et al. (2001) demonstrated that these mutations render beta-4 unable to interact with plectin and prevent the localization of plectin in hemidesmosomes. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Intermediate Junctional Epidermolysis Bullosa 5A</em></strong></p><p>
|
|
Inoue et al. (2000) studied a 68-year-old Japanese man with typical features of non-Herlitz JEB without pyloric atresia (JEB5A; 618716) who had a homozygous missense mutation in the ITGB4 gene (G931D; 147557.0012). He had lifelong trauma-induced skin fragility, but no history of gastrointestinal symptoms or previous abdominal surgery. </p><p>In a 49-year-old woman with mild blistering of hands and feet from birth, dystrophy of the nails with onychogryposis, and enamel hypoplasia, without pyloric atresia, Jonkman et al. (2002) identified a heterozygous 2-bp deletion in the ITGB4 gene (147557.0013). She was also expected to be heterozygous for a null allele, as no full-size protein was detected in vitro and the epitope 450-11 A was absent in vivo. </p><p><strong><em>Junctional Epidermolysis Bullosa 5B with Pyloric Atresia</em></strong></p><p>
|
|
Vidal et al. (1995) identified 2 mutations in compound heterozygosity (147557.0001 and 147557.0002) in a patient with junctional epidermolysis bullosa associated with pyloric atresia (JEB5B; 226730). </p><p>Improvement with aging has been reported in a few cases of epidermolysis bullosa with pyloric atresia. In a patient who improved from severe to mild JEB-PA, Chavanas et al. (1999) found compound heterozygosity for 2 splice site mutations in the ITGB4 gene (147557.0011 and 147557.0007). Analysis of the mRNA showed that 1 of the mutations prevented legitimate splicing of the beta-4 pre-mRNA. Functional splicing could be restored in vitro by seeding the patient's keratinocytes on feeders of irradiated fibroblasts. Study of mRNA in wildtype keratinocytes transfected with ITGB4 minigenes containing intron 31 with or without the mutation confirmed the causative role in JEB-PA. </p><p>Nakano et al. (2001) identified 11 novel mutations in ITGB4 in patients with epidermolysis bullosa with congenital pyloric atresia. Four mutations predicted a premature termination codon and 7 were missense mutations. Of the 33 mutations reported to that time, those causing premature termination codons were associated with the lethal variant, whereas missense mutations were more prevalent in nonlethal forms. In general, indirect immunofluorescent studies of affected skin revealed negative staining for beta-4 integrin in lethal cases and positive, but attenuated, staining in nonlethal cases and correlated with clinical phenotype. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In addition to promoting cell adhesion and cytoskeletal organization, basement membranes influence the proliferation and differentiation of cells. The effects of basement membranes on cellular behavior are likely to be mediated by integrins. The cytoplasmic domain of the integrin beta-4 subunit mediates both association with the hemidesmosomal cytoskeleton and recruitment of the signaling adaptor protein SHC (600560). To examine the significance of these interactions during development, Murgia et al. (1998) generated mice carrying a targeted deletion of the beta-4 cytoplasmic domain. Analysis of homozygous mutant mice indicated that the tail-less alpha-6/beta-4 binds efficiently to laminin-5 (see 600805), but is unable to integrate with the cytoskeleton. Accordingly, these mice displayed extensive epidermal detachment at birth and died immediately thereafter from a syndrome resembling junctional epidermolysis bullosa with pyloric atresia in humans. In addition, Murgia et al. (1998) found a significant proliferative defect. Specifically, the number of precursor cells in the intestinal epithelium, which remains adherent to the basement membrane, and in intact areas of the skin was reduced, and postmitotic enterocytes displayed increased levels of the cyclin-dependent kinase inhibitor p27(Kip) (600778). These findings indicated that the interactions mediated by the beta-4 tail are crucial for stable adhesion of stratified epithelia to the basement membrane and for proper cell cycle control of the proliferative compartments of both stratified and simple epithelia. </p><p>Amplification of ERBB2 (164870) is common in aggressive breast tumors and correlates with poor prognosis. Guo et al. (2006) found that deletion of the signaling domain of beta-4 integrin suppressed tumor onset and invasive growth in a mouse model of Erbb2-induced mammary carcinoma. Ex vivo studies showed that beta-4 formed a complex with Erbb2 and enhanced activation of Stat3 (102582) and Jun (165160). Stat3 contributed to disruption of epithelial adhesion and polarity, whereas Jun was required for hyperproliferation. Deletion of the beta-4 signaling domain enhanced the efficacy of Erbb2-targeted therapy. Guo et al. (2006) concluded that beta-4 integrin promotes tumor progression by amplifying ERBB2 signaling and is a potential target for breast cancer therapy. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>16 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, 1-BP INS, 3801T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs886041205,
|
|
|
|
|
|
|
|
ClinVar: RCV000401703, RCV002280814
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Vidal et al. (1995) found compound heterozygosity for mutations in the ITGB4 gene in an infant with junctional epidermolysis bullosa associated with pyloric atresia (JEB5B; 226730). The parents were unaffected and unrelated. At birth, the infant presented with pyloric atresia and cutaneous aplasia of the left hand. Perioral blistering and erosions of the mucosa of the mouth, upper esophagus, and cornea were noted shortly after birth. Pyloric atresia was treated surgically at the age of 2 weeks. During a surgical procedure at the age of 8 weeks, erosions of the gastric epithelium were found. At the age of 8 months, infection of skin blisters resulted in generalized infection and death of the infant. In the allele inherited from the mother, an insertion of a T was found after the second base at the 5-prime end of the intron after nucleotide 3801. This was predicted to result in shortening of the cytoplasmic domain of the integrin beta-4 subunit. The mutation was designated 3801+2insT. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, 1-BP DEL, 1150G
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000015851
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with JEB associated with pyloric atresia (JEB5B; 226730), Vidal et al. (1995) found that the mutant allele inherited from the father had deletion of the ITGB4 cDNA sequence. This mutation, 1150delG, resulted in a premature termination codon 168-bp downstream from the deletion, predicting a truncated beta-4 polypeptide terminating at residue 409. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, LEU156PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912461,
|
|
|
|
|
|
|
|
ClinVar: RCV000015853
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mutation in the ITGA6 and ITGB4 genes had been demonstrated in patients with a lethal form of epidermolysis bullosa with congenital pyloric atresia (JEB5B; 226730). Pulkkinen et al. (1998) provided the first demonstration of ITGB4 mutations in nonlethal epidermolysis bullosa with congenital pyloric atresia. The patient was compound heterozygous for a missense mutation (L156P) and a nonsense mutation (R554X; 147557.0004). The leucine substitution by proline affected a residue conserved in different human, rodent, and Drosophila integrin-beta polypeptides and disrupts the alpha-helix formation of the polypeptide segment. The nonsense mutation was accompanied by undetectable levels of the corresponding mRNA transcript, as determined by RT-PCR. The presence of a missense mutation, when combined with a premature termination codon mutation, may explain the milder blistering tendency of the skin in this patient. The proband was an 18-month-old male, the product of a nonconsanguineous union. Pyloric atresia was diagnosed at birth and treated surgically at the age of 3 days. Following the operation, skin blistering was noted at sites exposed to mechanical trauma, and the blisters healed without apparent scarring, milia, or pigmentary changes. Later on, however, only occasional blisters developed, mostly at the sites of trauma such as the knees and toes, and dystrophy of some toenails developed. The mucous membranes were not involved. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, ARG554TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912462,
|
|
|
|
|
|
gnomAD: rs121912462,
|
|
|
|
|
|
ClinVar: RCV000015854, RCV005016271
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg554-to-ter (R554X) mutation in the ITGB4 gene that was found in compound heterozygous state in a patient with lethal epidermolysis bullosa with congenital pyloric atresia (JEB5B; 226730) by Pulkkinen et al. (1998), see 147557.0003. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, CYS61TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80338755,
|
|
|
|
|
|
gnomAD: rs80338755,
|
|
|
|
|
|
ClinVar: RCV000015855, RCV000413122, RCV002504794, RCV003156061
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Pulkkinen et al. (1998) pointed out that patients with the lethal variant of epidermolysis bullosa with pyloric atresia (JEB5B; 226730) usually have mutations leading to premature termination of the protein, whereas missense mutations may lead to nonlethal phenotypes. A missense mutation that resulted in a lethal phenotype involved a cysteine residue (C61Y). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, CYS562ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912463,
|
|
|
|
|
|
gnomAD: rs121912463,
|
|
|
|
|
|
ClinVar: RCV000015856, RCV005089264
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Pulkkinen et al. (1998) found 1 of 3 patients with a nonlethal form of epidermolysis bullosa with pyloric atresia (JEB5B; 226730) to be homozygous for a cys562-to-arg (C562R) missense mutation in the ITGB4 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, IVS30DS, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs147222357,
|
|
|
|
|
|
gnomAD: rs147222357,
|
|
|
|
|
|
ClinVar: RCV000015857, RCV000255841
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mellerio et al. (1998) reported 2 unrelated patients with junctional epidermolysis bullosa with pyloric atresia (JEB5B; 226730) who survived into early childhood with mild cutaneous involvement. One patient was compound heterozygous for a splice site mutation in exon 30 (3793+1G-A) and a nonsense mutation in exon 36 (W1478X; 147557.0008). The second patient was compound heterozygous with a missense mutation in exon 3 (C38R; 147557.0009) and a 1-bp deletion in exon 36 (4776delG; 147557.0010). Although the nonsense and deletion mutations were predicted to result in markedly reduced beta-4 integrin mRNA levels, the presence of the missense or splice site mutation on the second allele may enable the synthesis of some functional, albeit perturbed, beta-4 polypeptide. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, TRP1478TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912464,
|
|
|
|
|
|
|
|
ClinVar: RCV000015858
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the trp1478-to-ter (W1478X) mutation in the ITGB4 gene that was found in compound heterozygous state in a patient with junctional epidermolysis bullosa with pyloric atresia (JEB5B; 226730) by Mellerio et al. (1998), see 147557.0007. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, CYS38ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912465,
|
|
|
|
|
|
|
|
ClinVar: RCV000015859
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the cys38-to-arg (C38R) mutation in the ITGB4 gene that was found in compound heterozygous state in a patient with junctional epidermolysis bullosa with pyloric atresia (JEB5B; 226730) by Mellerio et al. (1998), see 147557.0007. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, 1-BP DEL, 4776G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs794726676,
|
|
|
|
|
|
|
|
ClinVar: RCV000015852, RCV005025059
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion in the ITGB4 gene (4776delG) that was found in compound heterozygous state in a patient with junctional epidermolysis bullosa with pyloric atresia (JEB5B; 226730) by Mellerio et al. (1998), see 147557.0007. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, IVS31DS, T-A, -19
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1434530468,
|
|
|
|
|
|
gnomAD: rs1434530468,
|
|
|
|
|
|
ClinVar: RCV000015860, RCV003556028
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Chavanas et al. (1999) reported a patient who represented the rare instance in which epidermolysis bullosa with pyloric atresia (JEB5B; 226730) shows improvement with age. The proband was a 14-year-old boy, the child of nonconsanguineous parents, who at birth presented all the hallmarks of severe PA-JEB, including extensive skin blistering, pyloric atresia, and urethrovesical occlusion. As the child grew, however, the blistering tendency decreased and his skin and epithelia acquired resistance to trauma. At the age of 14, induction of blisters required prolonged rubbing of the skin. In this patient, Chavanas et al. (1999) found compound heterozygosity for the intron 30 splice donor site mutation (3802+1G-A; 147557.0007) and a novel T-to-A transversion at nucleotide 3986-19 in intron 31 of the ITGB4 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5A, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, GLY931ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912466,
|
|
|
|
|
|
|
|
ClinVar: RCV002051629
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 68-year-old male with typical non-Herlitz junctional epidermolysis bullosa (JEB5A; 619816) without pyloric atresia, Inoue et al. (2000) reported a homozygous ITGB4 gly931-to-asp (G931D) mutation. The patient, who was the product of a consanguineous mating, had a history of congenital blisters, recurrent urethral stenosis since age 12 years, progressive alopecia since childhood, loss of permanent dentition by age 30 years, nail dystrophy, and absence of pubic and axillary hair. There was no history of gastrointestinal symptoms or previous abdominal surgery. The mutation, a G-to-A transition at nucleotide 2792, created a novel BsmF1 cut site. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5A, INTERMEDIATE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, 2-BP DEL, 4733CT
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV002051630
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Jonkman et al. (2002) reported a patient with predominant features of epidermolysis bullosa simplex confined to the hands and feet (JEB5A; 619816) due to a heterozygous 2-bp deletion (4733delCT) in the ITGB4 gene, resulting in in-frame skipping of exon 36 and a deduced 50-amino acid deletion (1450-1499) within the third fibronectin type III repeat in the cytoplasmic domain of integrin beta-4. Although mutation in exon 36 of the ITGB4 gene had been reported in epidermolysis bullosa with pyloric atresia (226730) (see 147557.0007), this patient had no history of pyloric atresia. The patient, a 49-year-old female, had mild blistering of hands and feet from birth, dystrophy of the nails with onychogryposis, and enamel hypoplasia. Electron microscopy and antigen mapping of a skin blister revealed that the level of separation was intraepidermal, low in the basal keratinocytes through the attachment plaque of the hemidesmosome. Immunofluorescence microscopy revealed absent binding of monoclonal antibody 450-11 A against the third fibronectin III repeat on the intracellular domain of integrin beta-4, whereas binding was reduced with monoclonal antibodies recognizing epitopes on amino-terminal and carboxy-terminal ends of the polypeptide. Immunoblot analysis demonstrated a 5-kD shorter beta-4 polypeptide. The patient was also expected to be heterozygous for a null allele, as no full-size protein was detected in vitro and the epitope 450-11 A was absent in vivo. These data showed that deletion of the third fibronectin type III repeat in the cytoplasmic domain of integrin beta-4, which is thought to interact with BP180/type XVII collagen (113811), is clinically pathogenic and results in a mild phenotype. Although Jonkman et al. (2002) stated that the level of skin separation was intraepidermal (i.e., consistent with that seen in epidermolysis bullosa simplex), they pointed out that 'pseudojunctional' splits very low in the basal cells had been reported in patients with JEB with pyloric atresia carrying mutations in the ITGB4 gene (e.g., Pulkkinen et al. (1998), Mellerio et al. (1998)). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, ARG1281TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912467,
|
|
|
|
|
|
gnomAD: rs121912467,
|
|
|
|
|
|
ClinVar: RCV000015863, RCV000359496, RCV004586010, RCV005016272
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with epidermolysis bullosa with pyloric atresia (JEB5B; 226730), Pulkkinen et al. (1998) described an arg1281-to-trp (R1281W) mutation in the ITGB4 gene. In 1 patient the mutation was homozygous, and in the other compound heterozygous with another missense mutation. Koster et al. (2001) reported that this mutation renders integrin beta-4 unable to interact with plectin (601282) and prevents the localization of plectin in hemidesmosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, ARG1225HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912468,
|
|
|
|
|
|
gnomAD: rs121912468,
|
|
|
|
|
|
ClinVar: RCV000015864
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an individual with epidermolysis bullosa with pyloric atresia (JEB5B; 226730), Nakano et al. (2001) found an arg1225-to-his (R1225H) mutation in the ITGB4 gene. The mutation occurred in compound heterozygosity. The blistering tendency of the patient improved with time. Koster et al. (2001) reported that this mutation renders integrin beta-4 unable to interact with plectin (601282) and prevents the localization of plectin in hemidesmosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 EPIDERMOLYSIS BULLOSA, JUNCTIONAL 5B, WITH PYLORIC ATRESIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ITGB4, 2,279-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000015865
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of the original Bedouin kindred from southern Israel with epidermolysis bullosa with pyloric atresia and aplasia cutis congenita (JEB5B; 226730), described by Carmi et al. (1982) and Maman et al. (1998), Birnbaum et al. (2008) identified a homozygous 2,279-bp in-frame deletion in part of exon 27 and all of exons 28-30 of the ITGB4 gene in 3 affected family members. The deletion includes the authentic 5-prime splice site of exon 27 that creates a new cryptic 5-prime splice site leading to a 570-bp deletion within the integrin beta-4 final transcript. The mutation generates an in-frame deletion of 190 amino acids (1075-1266). The ITGB4 fragment deleted in this family encodes the first pair of fibronectin type III (FNIII) repeats. Birnbaum et al. (2008) suggested that the deletion affected the integrity of the basement membrane and the assembly of hemidesmosomes, consequently abrogating the control of normal skin structure. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Birnbaum, R. Y., Landau, D., Elbedour, K., Ofir, R., Birk, O. S., Carmi, R.
|
|
<strong>Deletion of the first pair of fibronectin type III repeats of the integrin beta-4 gene is associated with epidermolysis bullosa, pyloric atresia and aplasia cutis congenita in the original Carmi syndrome patients. (Letter)</strong>
|
|
Am. J. Med. Genet. 146A: 1063-1066, 2008.
|
|
|
|
|
|
[PubMed: 18348258]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31903]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Carmi, R., Sofer, S., Karplus, M., Ben-Yakar, Y., Mahler, D., Zirkin, H., Bar-Ziv, J.
|
|
<strong>Aplasia cutis congenita in two sibs discordant for pyloric atresia.</strong>
|
|
Am. J. Med. Genet. 11: 319-328, 1982.
|
|
|
|
|
|
[PubMed: 6177243]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320110308]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chavanas, S., Gache, Y., Vailly, J., Kanitakis, J., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G.
|
|
<strong>Splicing modulation of integrin beta-4 pre-mRNA carrying a branch point mutation underlies epidermolysis bullosa with pyloric atresia undergoing spontaneous amelioration with ageing.</strong>
|
|
Hum. Molec. Genet. 8: 2097-2105, 1999.
|
|
|
|
|
|
[PubMed: 10484780]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/8.11.2097]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dajee, M., Lazarov, M., Zhang, J. Y., Cai, T., Green, C. L., Russell, A. J., Marinkovich, M. P., Tao, S., Lin, Q., Kubo, Y., Khavari, P. A.
|
|
<strong>NF-kappa-B blockade and oncogenic Ras trigger invasive human epidermal neoplasia.</strong>
|
|
Nature 421: 639-643, 2003.
|
|
|
|
|
|
[PubMed: 12571598]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature01283]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Geerts, D., Fontao, L., Nievers, M. G., Schaapveld, R. Q. J., Purkis, P. E., Wheeler, G. N., Lane, E. B., Leigh, I.M., Sonnenberg, A.
|
|
<strong>Binding of integrin alpha-6-beta-4 to plectin prevents plectin association with F-actin but does not interfere with intermediate filament binding.</strong>
|
|
J. Cell Biol. 147: 417-434, 1999.
|
|
|
|
|
|
[PubMed: 10525545]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1083/jcb.147.2.417]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guo, W., Pylayeva, Y., Pepe, A., Yoshioka, T., Muller, W. J., Inghirami, G., Giancotti, F. G.
|
|
<strong>Beta-4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis.</strong>
|
|
Cell 126: 489-502, 2006.
|
|
|
|
|
|
[PubMed: 16901783]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2006.05.047]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hogervorst, F., Kuikman, I., Geurts van Kessel, A., Sonnenberg, A.
|
|
<strong>Molecular cloning of the human alpha-6 integrin subunit: alternative splicing of alpha-6 mRNA and chromosomal localization of the alpha-6 and beta-4 genes.</strong>
|
|
Europ. J. Biochem. 199: 425-433, 1991.
|
|
|
|
|
|
[PubMed: 2070796]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1432-1033.1991.tb16140.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hogervorst, F., Kuikman, I., von dem Borne, A. E., Sonnenberg, A.
|
|
<strong>Cloning and sequence analysis of beta-4 cDNA: an integrin subunit that contains a unique 118 kd cytoplasmic domain.</strong>
|
|
EMBO J. 9: 765-770, 1990.
|
|
|
|
|
|
[PubMed: 2311578]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1990.tb08171.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Inoue, M., Tamai, K., Shimizu, H., Owaribe, K., Nakama, T., Hashimoto, T., McGrath, J. A.
|
|
<strong>A homozygous missense mutation in the cytoplasmic tail of beta-4 integrin, G931D, that disrupts hemidesmosome assembly and underlies non-Herlitz junctional epidermolysis bullosa without pyloric atresia?</strong>
|
|
J. Invest. Derm. 114: 1061-1064, 2000.
|
|
|
|
|
|
[PubMed: 10792571]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1523-1747.2000.00960-3.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jonkman, M. F., Pas, H. H., Nijenhuis, M., Kloosterhuis, G., van der Steege, G.
|
|
<strong>Deletion of a cytoplasmic domain of integrin beta-4 causes epidermolysis bullosa simplex.</strong>
|
|
J. Invest. Derm. 119: 1275-1281, 2002.
|
|
|
|
|
|
[PubMed: 12485428]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1523-1747.2002.19609.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koster, J., Kuikman, I., Kreft, M., Sonnenberg, A.
|
|
<strong>Two different mutations in the cytoplasmic domain of the integrin 4 subunit in nonlethal forms of epidermolysis bullosa prevent interaction of 4 with plectin.</strong>
|
|
J. Invest. Derm. 117: 1405-1411, 2001. Note: Erratum: J. Invest. Derm. 118: 910 only, 2002.
|
|
|
|
|
|
[PubMed: 11886501]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.0022-202x.2001.01567.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maman, E., Maor, E., Kachko, L., Carmi, R.
|
|
<strong>Epidermolysis bullosa, pyloric atresia, aplasia cutis congenita: histopathological delineation of an autosomal recessive disease.</strong>
|
|
Am. J. Med. Genet. 78: 127-133, 1998.
|
|
|
|
|
|
[PubMed: 9674902]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mellerio, J. E., Pulkkinen, L., McMillan, J. R., Lake, B. D., Horn, H. M., Tidman, M. J., Harper, J. I., McGrath, J. A., Uitto, J., Eady, R. A. J.
|
|
<strong>Pyloric atresia-junctional epidermolysis bullosa syndrome: mutations in the integrin beta-4 gene (ITGB4) in two unrelated patients with mild disease.</strong>
|
|
Brit. J. Derm. 139: 862-871, 1998.
|
|
|
|
|
|
[PubMed: 9892956]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2133.1998.02515.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murgia, C., Blaikie, P., Kim, N., Dans, M., Petrie, H. T., Giancotti, F. G.
|
|
<strong>Cell cycle and adhesion defects in mice carrying a targeted deletion of the integrin beta-4 cytoplasmic domain.</strong>
|
|
EMBO J. 17: 3940-3951, 1998.
|
|
|
|
|
|
[PubMed: 9670011]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/emboj/17.14.3940]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakano, A., Pulkkinen, L., Murrell, D., Rico, J., Lucky, A. W., Garzon, M., Stevens, C. A., Robertson, S., Pfendner, E., Uitto, J.
|
|
<strong>Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta-4 integrin gene (ITGB4) and genotype/phenotype correlations.</strong>
|
|
Pediat. Res. 49: 618-626, 2001.
|
|
|
|
|
|
[PubMed: 11328943]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-200105000-00003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Niessen, C. M., Hulsman, E. H. M., Rots, E. S., Sanchez-Aparicio, P., Sonnenberg, A.
|
|
<strong>Integrin alpha-6-beta-4 forms a complex with the cytoskeletal protein HD1 and induces its redistribution in transfected COS-7 cells.</strong>
|
|
Molec. Biol. Cell 8: 555-566, 1997.
|
|
|
|
|
|
[PubMed: 9247637]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1091/mbc.8.4.555]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nievers, M. G., Schaapveld, R. Q. J., Oomen, L. C. J. M., Fontao, L., Geerts, D., Sonnenberg, A.
|
|
<strong>Ligand-independent role of the beta-4 integrin subunit in the formation of hemidesmosomes.</strong>
|
|
J. Cell Sci. 111: 1659-1672, 1998.
|
|
|
|
|
|
[PubMed: 9601096]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1242/jcs.111.12.1659]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pulkkinen, L., Bruckner-Tuderman, L., August, C., Uitto, J.
|
|
<strong>Compound heterozygosity for missense mutation (L156P) and nonsense (R554X) mutations in the beta-4 integrin gene (ITGB4) underlies mild, nonlethal phenotype of epidermolysis bullosa with pyloric atresia.</strong>
|
|
Am. J. Path. 152: 935-941, 1998.
|
|
|
|
|
|
[PubMed: 9546354]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pulkkinen, L., Rouan, F., Bruckner-Tuderman, L., Wallerstein, R., Garzon, M., Brown, T., Smith, L., Carter, W., Uitto, J.
|
|
<strong>Novel ITGB4 mutations in lethal and nonlethal variants of epidermolysis bullosa with pyloric atresia: missense versus nonsense.</strong>
|
|
Am. J. Hum. Genet. 63: 1376-1387, 1998.
|
|
|
|
|
|
[PubMed: 9792864]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302116]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shaw, L. M., Rabinovitz, I., Wang, H. H.-F., Toker, A., Mercurio, A. M.
|
|
<strong>Activation of phosphoinositide 3-OH kinase by the alpha-6/beta-4 integrin promotes carcinoma invasion.</strong>
|
|
Cell 91: 949-960, 1997.
|
|
|
|
|
|
[PubMed: 9428518]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)80486-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Suzuki, S., Naitoh, Y.
|
|
<strong>Amino acid sequence of a novel integrin beta-4 subunit and primary expression of the mRNA in epithelial cells.</strong>
|
|
EMBO J. 9: 757-763, 1990.
|
|
|
|
|
|
[PubMed: 2311577]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1990.tb08170.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vidal, F., Aberdam, D., Miquel, C., Christiano, A. M., Pulkkinen, L., Uitto, J., Ortonne, J.-P., Meneguzzi, G.
|
|
<strong>Integrin beta-4 mutations associated with junctional epidermolysis bullosa with pyloric atresia.</strong>
|
|
Nature Genet. 10: 229-234, 1995.
|
|
|
|
|
|
[PubMed: 7545057]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0695-229]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yang, L., Zhang, L., Wu, Q., Boyd, D. D.
|
|
<strong>Unbiased screening for transcriptional targets of ZKSCAN3 identifies integrin beta-4 and vascular endothelial growth factor as downstream targets.</strong>
|
|
J. Biol. Chem. 283: 35295-35304, 2008.
|
|
|
|
|
|
[PubMed: 18940803]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M806965200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Patricia A. Hartz - updated : 5/19/2009<br>Kelly A. Przylepa - updated : 2/5/2009<br>Matthew B. Gross - updated : 2/8/2007<br>Anne M. Stumpf - reorganized : 5/21/2003<br>Gary A. Bellus - updated : 5/21/2003<br>Gary A. Bellus - updated : 5/13/2003<br>Ada Hamosh - updated : 2/13/2002<br>Gary A. Bellus - updated : 6/12/2000<br>Victor A. McKusick - updated : 10/25/1999<br>Victor A. McKusick - updated : 2/1/1999<br>Victor A. McKusick - updated : 12/8/1998<br>Victor A. McKusick - updated : 10/7/1998<br>Victor A. McKusick - updated : 7/2/1998<br>Stylianos E. Antonarakis - updated : 2/20/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 3/3/1992
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 03/29/2022<br>mcolton : 06/15/2015<br>terry : 4/1/2013<br>terry : 6/11/2012<br>mgross : 5/19/2009<br>carol : 2/5/2009<br>terry : 2/5/2009<br>carol : 7/9/2008<br>ckniffin : 7/2/2008<br>ckniffin : 5/29/2008<br>ckniffin : 5/23/2008<br>wwang : 2/22/2007<br>mgross : 2/8/2007<br>wwang : 12/20/2006<br>cwells : 11/10/2003<br>cwells : 11/10/2003<br>alopez : 5/21/2003<br>alopez : 5/21/2003<br>carol : 5/14/2003<br>alopez : 5/13/2003<br>alopez : 2/13/2002<br>terry : 2/13/2002<br>terry : 6/7/2001<br>alopez : 6/12/2000<br>alopez : 6/12/2000<br>mgross : 11/5/1999<br>terry : 10/25/1999<br>carol : 2/3/1999<br>terry : 2/1/1999<br>carol : 12/11/1998<br>terry : 12/8/1998<br>carol : 10/14/1998<br>terry : 10/7/1998<br>terry : 8/24/1998<br>carol : 7/13/1998<br>terry : 7/2/1998<br>dholmes : 2/20/1998<br>dholmes : 2/20/1998<br>dholmes : 2/19/1998<br>terry : 7/1/1996<br>terry : 7/1/1996<br>mark : 6/1/1995<br>supermim : 3/16/1992<br>carol : 3/3/1992
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|