4366 lines
433 KiB
Text
4366 lines
433 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
|
|
|
|
- *601573 - ENHANCER OF ZESTE 2 POLYCOMB REPRESSIVE COMPLEX 2 SUBUNIT; EZH2
|
|
|
|
|
|
- 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=601573"><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">*601573</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="#description">Description</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="#geneStructure">Gene Structure</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="#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/601573">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=ENSG00000106462;t=ENST00000320356" 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=2146" 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=601573" 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=ENSG00000106462;t=ENST00000320356" 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_001203247,NM_001203248,NM_001203249,NM_004456,NM_152998,XM_005249962,XM_005249963,XM_005249964,XM_011515883,XM_011515885,XM_011515887,XM_011515889,XM_011515890,XM_011515892,XM_011515893,XM_011515894,XM_011515895,XM_011515896,XM_011515899,XM_011515901,XM_017011817,XM_017011819,XM_017011820,XM_047419989,XM_047419990,XM_047419991,XM_047419992,XM_047419993,XM_047419994,XM_047419995,XM_047419996,XM_047419997,XM_047419998,XM_047419999,XM_047420000,XM_047420001,XM_047420002,XM_047420004,XM_047420005,XM_047420006,XM_047420007,XM_047420008,XM_047420009" 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_004456" 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=601573" 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=03342&isoform_id=03342_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/EZH2" 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/1279913,1438064,1575349,3334180,3713992,14790029,21361095,23510384,41393512,41393513,41472411,41618700,51105823,51105824,62087370,119600473,119600474,119600475,119600476,189067238,193787386,221039418,221043950,221044628,221044650,322506097,322506099,322506101,326786804,345286379,440575835,530386930,530386932,530386934,767947033,767947038,767947043,767947047,767947049,767947053,767947055,767947057,767947059,767947062,767947068,767947072,1034654383,1034654401,1034654404,2217365937,2217365941,2217365943,2217365946,2217365949,2217365951,2217365953,2217365956,2217365958,2217365964,2217365969,2217365971,2217365973,2217365977,2217365980,2217365982,2217365984,2217365987,2217365989,2217365992,2462612829,2462612831,2462612833,2462612835,2462612838,2462612840,2462612842,2462612844,2462612846,2462612848,2462612850,2462612852,2462612854,2462612856,2462612858,2462612860,2462612862,2462612864,2462612866,2462612868,2462612870,2462612872,2462612874,2462612876,2462612878,2462612880,2462612882,2462612884,2462612886,2462612888,2462612890,2462612892,2462612894,2462612896,2462612898,2462612900,2462612902,2508231843,2508231845,2508231847,2508231849,2508231851,2508231853,2508231855,2508231857,2508231859,2508231861,2508231863,2508231865" 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/Q15910" 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=2146" 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=ENSG00000106462;t=ENST00000320356" 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=EZH2" 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=EZH2" 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+2146" 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/EZH2" 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:2146" 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/2146" 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=chr7&hgg_gene=ENST00000320356.7&hgg_start=148807383&hgg_end=148884291&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://search.clinicalgenome.org/kb/genes/HGNC:3527" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/ezh2" 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=601573[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=601573[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://www.deciphergenomics.org/gene/EZH2/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000106462" 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=EZH2" 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=EZH2" 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=EZH2" 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="http://www.LOVD.nl/EZH2" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=EZH2&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/PA27939" 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:3527" 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/FBgn0000629.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:107940" 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/EZH2#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:107940" 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/2146/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://www.orthodb.org/?ncbi=2146" 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://wormbase.org/db/gene/gene?name=WBGene00003220;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-041111-259" 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:2146" 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=EZH2&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">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 63119004<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> Q87.3<br />
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
601573
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ENHANCER OF ZESTE 2 POLYCOMB REPRESSIVE COMPLEX 2 SUBUNIT; EZH2
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
ENHANCER OF ZESTE, DROSOPHILA, HOMOLOG 2<br />
|
|
ENX1
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</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=EZH2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">EZH2</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/7/790?start=-3&limit=10&highlight=790">7q36.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:148807383-148884291&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">7:148,807,383-148,884,291</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
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/790?start=-3&limit=10&highlight=790">
|
|
7q36.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Weaver syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/277590"> 277590 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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/601573" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/601573" 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>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</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="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The EZH2 gene encodes a histone methyltransferase that constitute the catalytic component of the polycomb repressive complex-2 (PRC2), which functions to initiate epigenetic silencing of genes involved in cell fate decisions. EZH2 specifically methylates nucleosomal histone H3 (see <a href="/entry/602810">602810</a>) at lysine-27 (H3-K27) (summary by <a href="#1" class="mim-tip-reference" title="Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., Zhang, Y. <strong>Role of histone H3 lysine 27 methylation in polycomb-group silencing.</strong> Science 298: 1039-1043, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351676</a>] [<a href="https://doi.org/10.1126/science.1076997" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12351676">Cao et al., 2002</a> and <a href="#11" class="mim-tip-reference" title="Ernst, T., Chase, A. J., Score, J., Hidalgo-Curtis, C. E., Bryant, C., Jones, A. V., Waghorn, K., Zoi, K., Ross, F. M., Reiter, A., Hochhaus, A., Drexler, H. G., Duncombe, A., Cervantes, F., Oscier, D., Boultwood, J., Grand, F. H., Cross, N. C. <strong>Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.</strong> Nature Genet. 42: 722-726, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20601953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20601953</a>] [<a href="https://doi.org/10.1038/ng.621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20601953">Ernst et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12351676+20601953" 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="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>To identify genes that map on human chromosome 21 that may contribute to the phenotype of Down syndrome, <a href="#6" class="mim-tip-reference" title="Chen, H., Rossier, C., Antonarakis, S. E. <strong>Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2.</strong> Genomics 38: 30-37, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8954776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8954776</a>] [<a href="https://doi.org/10.1006/geno.1996.0588" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8954776">Chen et al. (1996)</a> applied exon trapping to cosmid DNA from a chromosome 21-specific library. One of the potential exons that was cloned and partially characterized showed strong homology to the Drosophila 'enhancer of zeste' protein from amino acid 665 to amino acid 694. The Drosophila protein is a member of the Polycomb group, which maintains homeotic gene repression and is thought to control gene expression by regulating chromatin. <a href="#6" class="mim-tip-reference" title="Chen, H., Rossier, C., Antonarakis, S. E. <strong>Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2.</strong> Genomics 38: 30-37, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8954776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8954776</a>] [<a href="https://doi.org/10.1006/geno.1996.0588" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8954776">Chen et al. (1996)</a> cloned the full-length cDNA for this human homolog, termed EZH2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8954776" 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="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#2" class="mim-tip-reference" title="Cardoso, C., Mignon, C., Hetet, G., Grandchamps, B., Fontes, M., Colleaux, L. <strong>The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders.</strong> Europ. J. Hum. Genet. 8: 174-180, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10780782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10780782</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10780782">Cardoso et al. (2000)</a> reported the characteristics of all 20 exons of the EZH2 gene and the adjoining splice donor and splice acceptor sites and gave the size of the 19 introns. Transcription began near the beginning of exon 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10780782" 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="#6" class="mim-tip-reference" title="Chen, H., Rossier, C., Antonarakis, S. E. <strong>Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2.</strong> Genomics 38: 30-37, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8954776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8954776</a>] [<a href="https://doi.org/10.1006/geno.1996.0588" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8954776">Chen et al. (1996)</a> mapped the human EZH2 cDNA within YACs between marker D21S65 and ERG (<a href="/entry/165080">165080</a>) on 21q22.2. However, <a href="#2" class="mim-tip-reference" title="Cardoso, C., Mignon, C., Hetet, G., Grandchamps, B., Fontes, M., Colleaux, L. <strong>The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders.</strong> Europ. J. Hum. Genet. 8: 174-180, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10780782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10780782</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10780782">Cardoso et al. (2000)</a> later showed by FISH that the functional EZH2 gene maps to 7q35, not 21q22, and that the sequence isolated from the chromosome 21 cosmid corresponds to a pseudogene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8954776+10780782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By FISH, <a href="#16" class="mim-tip-reference" title="Laible, G., Haynes, A. R., Lebersorger, A., O'Carroll, D., Mattei, M.-G., Denny, P., Brown, S. D. M., Jenuwein, T. <strong>The murine polycomb-group genes Ezh1 and Ezh2 map close to Hox gene clusters on mouse chromosomes 11 and 6.</strong> Mammalian Genome 10: 311-314, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051331</a>] [<a href="https://doi.org/10.1007/s003359900993" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051331">Laible et al. (1999)</a> mapped the mouse Ezh2 gene to chromosome 6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051331" 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>Several lines of evidence suggested a critical role for the EZH2 protein during normal and perturbed development of the hematopoietic and central nervous systems. Indeed, the EZH2 protein has been shown to associate with the VAV1 protooncoprotein (<a href="/entry/164875">164875</a>) and with the XNP protein (<a href="/entry/300032">300032</a>), the product of a gene associated with mental retardation (<a href="#3" class="mim-tip-reference" title="Cardoso, C., Timsit, S., Villard, L., Khrestchatisky, M., Fontes, M., Colleaux, L. <strong>Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein.</strong> Hum. Molec. Genet. 7: 679-684, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9499421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9499421</a>] [<a href="https://doi.org/10.1093/hmg/7.4.679" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9499421">Cardoso et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9499421" 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 nature of the EZH2 protein and its mapping to the critical region for malignant myeloid disorders led <a href="#2" class="mim-tip-reference" title="Cardoso, C., Mignon, C., Hetet, G., Grandchamps, B., Fontes, M., Colleaux, L. <strong>The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders.</strong> Europ. J. Hum. Genet. 8: 174-180, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10780782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10780782</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10780782">Cardoso et al. (2000)</a> to propose that the EZH2 gene is involved in the pathogenesis of 7q35-q36 aberrations in myeloid leukemia (<a href="#10" class="mim-tip-reference" title="Dohner, K., Brown, J., Hehmann, U., Hetzel, C., Stewart, J., Lowther, G., Scholl, C., Frohling, S., Cuneo, A., Tsui, L. C., Lichter, P., Scherer, S. W., Dohner, H. <strong>Molecular cytogenetic characterization of a critical region in bands 7q35-q36 commonly deleted in malignant myeloid disorders.</strong> Blood 92: 4031-4035, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9834205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9834205</a>]" pmid="9834205">Dohner et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10780782+9834205" 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="#33" class="mim-tip-reference" title="Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., Rubin, M. A., Chinnaiyan, A. M. <strong>The polycomb group protein EZH2 is involved in progression of prostate cancer.</strong> Nature 419: 624-629, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12374981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12374981</a>] [<a href="https://doi.org/10.1038/nature01075" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12374981">Varambally et al. (2002)</a> demonstrated through gene expression profiling that EZH2 is overexpressed in hormone-refractory, metastatic prostate cancer (see <a href="/entry/176807">176807</a>). Small interfering RNA (siRNA) duplexes targeted against EZH2 reduced the amounts of EZH2 protein present in prostate cells and also inhibited cell proliferation in vitro. Ectopic expression of EZH2 in prostate cells induced transcriptional repression of a specific cohort of genes. Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity. Amounts of both EZH2 mRNA and EZH2 protein were increased in metastatic prostate cancer. In addition, clinically localized prostate cancers that expressed higher concentrations of EZH2 showed a poorer prognosis. Thus, <a href="#33" class="mim-tip-reference" title="Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., Rubin, M. A., Chinnaiyan, A. M. <strong>The polycomb group protein EZH2 is involved in progression of prostate cancer.</strong> Nature 419: 624-629, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12374981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12374981</a>] [<a href="https://doi.org/10.1038/nature01075" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12374981">Varambally et al. (2002)</a> concluded that dysregulated expression of EZH2 may be involved in the progression of prostate cancer as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12374981" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., Zhang, Y. <strong>Role of histone H3 lysine 27 methylation in polycomb-group silencing.</strong> Science 298: 1039-1043, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351676</a>] [<a href="https://doi.org/10.1126/science.1076997" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12351676">Cao et al. (2002)</a> reported the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. <a href="#1" class="mim-tip-reference" title="Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., Zhang, Y. <strong>Role of histone H3 lysine 27 methylation in polycomb-group silencing.</strong> Science 298: 1039-1043, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351676</a>] [<a href="https://doi.org/10.1126/science.1076997" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12351676">Cao et al. (2002)</a> demonstrated that the complex specifically methylates nucleosomal histone H3 (see <a href="/entry/601128">601128</a>) at lysine-27 (H3-K27). Using chromatin immunoprecipitation assays, <a href="#1" class="mim-tip-reference" title="Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., Zhang, Y. <strong>Role of histone H3 lysine 27 methylation in polycomb-group silencing.</strong> Science 298: 1039-1043, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351676</a>] [<a href="https://doi.org/10.1126/science.1076997" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12351676">Cao et al. (2002)</a> showed that H3-K27 methylation colocalizes with, and is dependent on, E(Z) binding at an 'Ultrabithorax' (Ubx) Polycomb response element, and that this methylation correlates with Ubx expression. Methylation on H3-K27 facilitates binding of Polycomb, a component of the Polycomb repressive complex 1 (PRC1 complex), to the histone H3 N-terminal tail. Thus, <a href="#1" class="mim-tip-reference" title="Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., Zhang, Y. <strong>Role of histone H3 lysine 27 methylation in polycomb-group silencing.</strong> Science 298: 1039-1043, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351676</a>] [<a href="https://doi.org/10.1126/science.1076997" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12351676">Cao et al. (2002)</a> concluded that their studies established a link between histone methylation and Polycomb group-mediated gene silencing. The complex responsible for histone methyltransferase activity included EZH2, SUZ12 (<a href="/entry/606245">606245</a>), and EED (<a href="/entry/605984">605984</a>). EZH2 contains a SET domain, a signature motif for all known histone lysine methyltransferases except the H3-K79 methyltransferase DOT1, and is therefore likely to be the catalytic subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12351676" 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="#27" class="mim-tip-reference" title="Plath, K., Fang, J., Mlynarczyk-Evans, S. K., Cao, R., Worringer, K. A., Wang, H., de la Cruz, C. C., Otte, A. P., Panning, B., Zhang, Y. <strong>Role of histone H3 lysine 27 methylation in X inactivation.</strong> Science 300: 131-135, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12649488/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12649488</a>] [<a href="https://doi.org/10.1126/science.1084274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12649488">Plath et al. (2003)</a> demonstrated that transient recruitment of the EED-EZH2 complex to the inactive X chromosome occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the inactive X depend on Xist (<a href="/entry/314670">314670</a>) RNA but are independent of its silencing function. <a href="#27" class="mim-tip-reference" title="Plath, K., Fang, J., Mlynarczyk-Evans, S. K., Cao, R., Worringer, K. A., Wang, H., de la Cruz, C. C., Otte, A. P., Panning, B., Zhang, Y. <strong>Role of histone H3 lysine 27 methylation in X inactivation.</strong> Science 300: 131-135, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12649488/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12649488</a>] [<a href="https://doi.org/10.1126/science.1084274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12649488">Plath et al. (2003)</a> concluded that taken together, their results suggest a role for EED-EZH2-mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the inactive X. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12649488" 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="Cha, T.-L., Zhou, B. P., Xia, W., Wu, Y., Yang, C.-C., Chen, C.-T., Ping, B., Otte, A. P., Hung, M.-C. <strong>Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3.</strong> Science 310: 306-310, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16224021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16224021</a>] [<a href="https://doi.org/10.1126/science.1118947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16224021">Cha et al. (2005)</a> showed that AKT (<a href="/entry/164730">164730</a>) phosphorylates EZH2 at serine-21 and suppresses its methyltransferase activity by impeding EZH2 binding to histone H3, which results in a decrease of lysine-27 trimethylation and derepression of silenced genes. <a href="#4" class="mim-tip-reference" title="Cha, T.-L., Zhou, B. P., Xia, W., Wu, Y., Yang, C.-C., Chen, C.-T., Ping, B., Otte, A. P., Hung, M.-C. <strong>Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3.</strong> Science 310: 306-310, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16224021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16224021</a>] [<a href="https://doi.org/10.1126/science.1118947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16224021">Cha et al. (2005)</a> concluded that their results imply that AKT regulates the methylation activity, through phosphorylation of EZH2, which may contribute to oncogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16224021" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Vire, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.-M., Bollen, M., Esteller, M., Di Croce, L., de Launoit, Y., Fuks, F. <strong>The polycomb group protein EZH2 directly controls DNA methylation.</strong> Nature 439: 871-874, 2006. Note: Erratum: Nature 446: 824 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16357870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16357870</a>] [<a href="https://doi.org/10.1038/nature04431" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16357870">Vire et al. (2006)</a> showed that the silencing pathways of the polycomb group (PcG) and DNA methyltransferases systems are mechanically linked. They found that the PcG protein EZH2 interacts--within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3)--with DNA methyltransferases DNMT1 (<a href="/entry/126375">126375</a>), DNMT3A (<a href="/entry/602769">602769</a>), and DNMT3B (<a href="/entry/602900">602900</a>) and associates with DNMT activity in vivo. Chromatin immunoprecipitations indicated that binding of DNMTs to several EZH2-repressed genes depends on the presence of EZH2. Furthermore, <a href="#34" class="mim-tip-reference" title="Vire, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.-M., Bollen, M., Esteller, M., Di Croce, L., de Launoit, Y., Fuks, F. <strong>The polycomb group protein EZH2 directly controls DNA methylation.</strong> Nature 439: 871-874, 2006. Note: Erratum: Nature 446: 824 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16357870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16357870</a>] [<a href="https://doi.org/10.1038/nature04431" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16357870">Vire et al. (2006)</a> showed by bisulfite genomic sequencing that EZH2 is required for DNA methylation of EZH2-target promoters. <a href="#34" class="mim-tip-reference" title="Vire, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.-M., Bollen, M., Esteller, M., Di Croce, L., de Launoit, Y., Fuks, F. <strong>The polycomb group protein EZH2 directly controls DNA methylation.</strong> Nature 439: 871-874, 2006. Note: Erratum: Nature 446: 824 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16357870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16357870</a>] [<a href="https://doi.org/10.1038/nature04431" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16357870">Vire et al. (2006)</a> concluded that their results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between 2 key epigenetic repression systems. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16357870" 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>As indicated by the work of <a href="#15" class="mim-tip-reference" title="Kamminga, L. M., Bystrykh, L. V., de Boer, A., Houwer, S., Douma, J., Weersing, E., Dontje, B., de Haan, G. <strong>The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion.</strong> Blood 107: 2170-2179, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16293602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16293602</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16293602[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/10.1182/blood-2005-09-3585" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16293602">Kamminga et al. (2006)</a>, EZH2 is, like latexin (LXN; <a href="/entry/609305">609305</a>), a stem cell regulator. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16293602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Varambally, S., Cao, Q., Mani, R.-S., Shankar, S., Wang, X., Ateeq, B., Laxman, B., Cao, X., Jing, X., Ramnarayanan, K., Brenner, J. C., Yu, J., Kim, J. H., Han, B., Tan, P., Kumar-Sinha, C., Lonigro, R. J., Palanisamy, N., Maher, C. A., Chinnaiyan, A. M. <strong>Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer.</strong> Science 322: 1695-1699, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19008416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19008416</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19008416[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1165395" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19008416">Varambally et al. (2008)</a> demonstrated that the expression and function of EZH2 in cancer cell lines are inhibited by microRNA 101 (MIRN101; see <a href="/entry/612511">612511</a>). Analysis of human prostate tumors revealed that MIRN101 expression decreases during cancer progression, paralleling an increase in EZH2 expression. One or both of the 2 genomic loci encoding MIRN101 were somatically lost in 37.5% of clinically localized prostate cancer (see <a href="/entry/176807">176807</a>) cells (6 of 16) and 66.7% of metastatic disease cells (22 of 33). <a href="#32" class="mim-tip-reference" title="Varambally, S., Cao, Q., Mani, R.-S., Shankar, S., Wang, X., Ateeq, B., Laxman, B., Cao, X., Jing, X., Ramnarayanan, K., Brenner, J. C., Yu, J., Kim, J. H., Han, B., Tan, P., Kumar-Sinha, C., Lonigro, R. J., Palanisamy, N., Maher, C. A., Chinnaiyan, A. M. <strong>Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer.</strong> Science 322: 1695-1699, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19008416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19008416</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19008416[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1165395" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19008416">Varambally et al. (2008)</a> proposed that the genomic loss of MIRN101 in cancer leads to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways, resulting in cancer progression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19008416" 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="#31" class="mim-tip-reference" title="Terranova,, R., Yokobayashi, S., Stadler, M. B., Otte, A. P., van Lohuizen, M., Orkin, S. H., Peters, A. H. F. M. <strong>Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos.</strong> Dev. Cell 15: 668-679, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18848501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18848501</a>] [<a href="https://doi.org/10.1016/j.devcel.2008.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18848501">Terranova et al. (2008)</a> found that mouse Ezh2 and Rnf2 (<a href="/entry/608985">608985</a>) were independently required for genomic contraction and repression of imprinted genes during early embryonic development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18848501" 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 gene silencing activity of the Polycomb repressive complex-2 (PRC2; see <a href="/entry/601674">601674</a>) depends on its ability to trimethylate lys27 of histone 3 (H3K27) by the catalytic SET domain of the EZH2 subunit and at least 2 other subunits of the complex: SUZ12 (<a href="/entry/606245">606245</a>) and EED (<a href="/entry/605984">605984</a>). <a href="#19" class="mim-tip-reference" title="Margueron, R., Justin, N., Ohno, K., Sharpe, M. L., Son, J., Drury, W. J., III, Voigt, P., Martin, S. R., Taylor, W. R., De Marco, V., Pirrotta, V., Reinberg, D., Gamblin, S. J. <strong>Role of the polycomb protein EED in the propagation of repressive histone marks.</strong> Nature 461: 762-767, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19767730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19767730</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19767730[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature08398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19767730">Margueron et al. (2009)</a> showed that the carboxy-terminal domain of EED specifically binds to histone tails carrying trimethyl-lysine residues associated with repressive chromatin marks, and that this leads to the allosteric activation of the methyltransferase activity of PRC2. Mutations in EED that prevent it from recognizing repressive trimethyl-lysine marks abolished the activation of PRC2 in vitro and, in Drosophila, reduced global methylation and disrupted development. <a href="#19" class="mim-tip-reference" title="Margueron, R., Justin, N., Ohno, K., Sharpe, M. L., Son, J., Drury, W. J., III, Voigt, P., Martin, S. R., Taylor, W. R., De Marco, V., Pirrotta, V., Reinberg, D., Gamblin, S. J. <strong>Role of the polycomb protein EED in the propagation of repressive histone marks.</strong> Nature 461: 762-767, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19767730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19767730</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19767730[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature08398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19767730">Margueron et al. (2009)</a> concluded that their findings suggested a model for the propagation of the H3K27 methyl-3 mark that accounts for the maintenance of repressive chromatin domains and for the transmission of a histone modification from mother to daughter cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19767730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Chen, H., Tu, S., Hsieh, J.-T. <strong>Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer.</strong> J. Biol. Chem. 280: 22437-22444, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15817459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15817459</a>] [<a href="https://doi.org/10.1074/jbc.M501379200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15817459">Chen et al. (2005)</a> showed that increased EZH2 expression in normal human prostate epithelial cells suppressed DAB2IP (<a href="/entry/609205">609205</a>) gene expression. In contrast, knockdown of endogenous EZH2 levels in prostate cancer cells via siRNA increased DAB2IP expression. In prostate cancer, but not normal prostate epithelial cells, an EZH2 complex that included EED and SUZ12 associated with the DAB2IP promoter and increased promoter occupancy by methylated H3K27 and HDAC1 (<a href="/entry/601241">601241</a>). Knockdown of EZH2 reduced the association of methylated H3K27 and HDAC1 with the DAB2IP promoter. <a href="#7" class="mim-tip-reference" title="Chen, H., Tu, S., Hsieh, J.-T. <strong>Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer.</strong> J. Biol. Chem. 280: 22437-22444, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15817459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15817459</a>] [<a href="https://doi.org/10.1074/jbc.M501379200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15817459">Chen et al. (2005)</a> concluded that DAB2IP is a target for EZH2-mediated gene silencing in prostate epithelium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15817459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Ezhkova, E., Pasolli, H. A., Parker, J. S., Stokes, N., Su, I., Hannon, G., Tarakhovsky, A., Fuchs, E. <strong>Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells.</strong> Cell 136: 1122-1135, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19303854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19303854</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19303854[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2008.12.043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19303854">Ezhkova et al. (2009)</a> found that expression of Ezh2 in mouse epidermal progenitor cells diminished concomitant with their embryonic differentiation and postnatal decline in proliferative activity. Conditional knockout of Ezh2 in basal keratinocytes resulted in thickened stratum corneum and granular layer and precocious acquisition of epidermal barrier function in the embryo. Molecularly, these changes correlated with global reduction of H3K27 trimethylation marks and specifically with derepression of a 2-Mb epidermal differentiation complex controlled by Ink4a (CDKN2A; <a href="/entry/600160">600160</a>)/Ink4b (CDKN2B; <a href="/entry/600431">600431</a>). Reduced histone modification at this locus permitted recruitment of the AP1 transcription factor (see <a href="/entry/165160">165160</a>) and expression of genes associated with epidermal differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19303854" 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 predominantly a mouse tumor model and genetic manipulation of human prostate cancer cells, <a href="#21" class="mim-tip-reference" title="Min, J., Zaslavsky, A., Fedele, G., McLaughlin, S. K., Reczek, E. E., De Raedt, T., Guney, I., Strochlic, D. E., MacConaill, L. E., Beroukhim, R., Bronson, R. T., Ryeom, S., Hahn, W. C., Loda, M., Cichowski, K. <strong>An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappa-B.</strong> Nature Med. 16: 286-294, 2010. Note: Erratum: Nature Med. 30: 1790 only, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20154697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20154697</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20154697[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20154697">Min et al. (2010)</a> showed that direct EZH2-mediated downregulation of DAB2IP induced an epithelial-to-mesenchymal transition (EMT) in the cancer cells and increased their metastatic potential. DAB2IP downregulation activated RAS (HRAS; <a href="/entry/190020">190020</a>) and NFKB (see <a href="/entry/164011">164011</a>). RAS activation drove cell growth, while NFKB activation triggered EMT and metastasis. <a href="#21" class="mim-tip-reference" title="Min, J., Zaslavsky, A., Fedele, G., McLaughlin, S. K., Reczek, E. E., De Raedt, T., Guney, I., Strochlic, D. E., MacConaill, L. E., Beroukhim, R., Bronson, R. T., Ryeom, S., Hahn, W. C., Loda, M., Cichowski, K. <strong>An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappa-B.</strong> Nature Med. 16: 286-294, 2010. Note: Erratum: Nature Med. 30: 1790 only, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20154697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20154697</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20154697[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20154697">Min et al. (2010)</a> found an inverse relationship between EZH2 and DAB2IP expression in human prostate cancer tissues and an inverse relationship between DAB2IP expression and tumor grade. <a href="#21" class="mim-tip-reference" title="Min, J., Zaslavsky, A., Fedele, G., McLaughlin, S. K., Reczek, E. E., De Raedt, T., Guney, I., Strochlic, D. E., MacConaill, L. E., Beroukhim, R., Bronson, R. T., Ryeom, S., Hahn, W. C., Loda, M., Cichowski, K. <strong>An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappa-B.</strong> Nature Med. 16: 286-294, 2010. Note: Erratum: Nature Med. 30: 1790 only, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20154697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20154697</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20154697[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20154697">Min et al. (2010)</a> concluded that epigenetic suppression of DAB2IP by EZH2 is a major mechanism of DAB2IP inactivation in human prostate cancer and increases metastatic potential. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20154697" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Xu, C.-R., Cole, P. A., Meyers, D. J., Kormish, J., Dent, S., Zaret, K. S. <strong>Chromatin 'prepattern' and histone modifiers in a fate choice for liver and pancreas.</strong> Science 332: 963-966, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21596989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21596989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21596989[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1202845" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21596989">Xu et al. (2011)</a> isolated mouse embryonic endoderm cells and assessed histone modifications at regulatory elements of silent genes that are activated upon liver or pancreas fate choices, and found that the liver and pancreas elements have distinct chromatin patterns. Furthermore, the histone acetyltransferase P300 (<a href="/entry/602700">602700</a>), recruited via bone morphogenetic protein (BMP; see <a href="/entry/600799">600799</a>) signaling, and the histone methyltransferase Ezh2 have modulatory roles in the fate choice. <a href="#36" class="mim-tip-reference" title="Xu, C.-R., Cole, P. A., Meyers, D. J., Kormish, J., Dent, S., Zaret, K. S. <strong>Chromatin 'prepattern' and histone modifiers in a fate choice for liver and pancreas.</strong> Science 332: 963-966, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21596989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21596989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21596989[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1202845" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21596989">Xu et al. (2011)</a> concluded that their studies revealed a functional 'prepattern' of chromatin states within multipotent progenitors and potential targets to modulate cell fate induction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21596989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Xu, K., Wu, Z. J., Groner, A. C., He, H. H., Cai. C., Lis, R. T., Wu, X., Stack, E. C., Loda, M., Liu, T., Xu, H., Cato, L., Thornton, J. E., Gregory, R. I., Morrissey, C., Vessella, R. L., Montironi, R., Magi-Galluzzi, C. Kantoff, P. W., Balk, S. P., Liu, X. S., Brown, M. <strong>EZH2 oncogenic activity in castration-resistant prostate cancer cells is polycomb-independent.</strong> Science 338: 1465-1469, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23239736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23239736</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23239736[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1227604" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23239736">Xu et al. (2012)</a> found that the oncogenic function of EZH2 in cells of castration-resistant prostate cancer (see <a href="/entry/176807">176807</a>) is independent of its role as a transcriptional repressor. Instead, it involves the ability of EZH2 to act as a coactivator for critical transcription factors including the androgen receptor (<a href="/entry/313700">313700</a>). This functional switch is dependent on phosphorylation of EZH2 and requires an intact methyltransferase domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23239736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Di Meglio, T., Kratochwil, C. F., Vilain, N., Loche, A., Vitobello, A., Yonehara, K., Hrycaj, S. M., Roska, B., Peters, A. H. F. M., Eichmann, A., Wellik, D., Ducret, S., Rijli, F. M. <strong>Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons.</strong> Science 339: 204-207, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23307742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23307742</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23307742[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1229326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23307742">Di Meglio et al. (2013)</a> investigated the role of histone methyltransferase Ezh2 in tangential migration of mouse precerebellar pontine nuclei, the main relay between neocortex and cerebellum. By counteracting the sonic hedgehog (see <a href="/entry/600725">600725</a>) pathway, Ezh2 represses netrin-1 (<a href="/entry/601614">601614</a>) in dorsal hindbrain, which allows normal pontine neuron migration. In Ezh2 mutants, ectopic netrin-1 derepression resulted in abnormal migration and supernumerary nuclei integrating in brain circuitry. Moreover, intrinsic topographic organization of pontine nuclei according to rostrocaudal progenitor origin was maintained throughout migration and correlated with patterned cortical input. Ezh2 maintains spatially restricted Hox expression, which, in turn, regulates differential expression of the repulsive receptor Unc5b (<a href="/entry/607870">607870</a>) in migrating neurons; together, they generate subsets with distinct responsiveness to environmental netrin-1. Thus, <a href="#9" class="mim-tip-reference" title="Di Meglio, T., Kratochwil, C. F., Vilain, N., Loche, A., Vitobello, A., Yonehara, K., Hrycaj, S. M., Roska, B., Peters, A. H. F. M., Eichmann, A., Wellik, D., Ducret, S., Rijli, F. M. <strong>Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons.</strong> Science 339: 204-207, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23307742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23307742</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23307742[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1229326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23307742">Di Meglio et al. (2013)</a> concluded that Ezh2-dependent epigenetic regulation of intrinsic and extrinsic transcriptional programs controls topographic neuronal guidance and connectivity in the cortico-ponto-cerebellar pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23307742" 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="#13" class="mim-tip-reference" title="Fillmore, C. M., Xu, C., Desai, P. T., Berry, J. M., Rowbotham, S. P., Lin, Y.-J., Zhang, H., Marquez, V. E., Hammerman, P. S., Wong, K.-K., Kim, C. F. <strong>EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors.</strong> Nature 520: 239-242, 2015. Note: Erratum: Nature 563: E27, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25629630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25629630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25629630[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25629630">Fillmore et al. (2015)</a> demonstrated that EZH2 inhibition has differential effects on the TopoII inhibitor response of nonsmall-cell lung cancers in vitro and in vivo. EGFR (<a href="/entry/131550">131550</a>) and BRG1 (<a href="/entry/603254">603254</a>) mutations are genetic biomarkers that predict enhanced sensitivity to TopoII inhibitor in response to EZH2 inhibition. BRG1 loss-of-function mutant tumors respond to EZH2 inhibition with increased S phase, anaphase bridging, apoptosis, and TopoII inhibitor sensitivity. Conversely, EGFR and BRG1 wildtype tumors upregulate BRG1 in response to EZH2 inhibition and ultimately become more resistant to TopoII inhibitor. EGFR gain-of-function mutant tumors are also sensitive to dual EZH2 inhibition and TopoII inhibitor, because of genetic antagonism between EGFR and BRG1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25629630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Peng, D., Kryczek, I., Nagarsheth, N., Zhao, L., Wei, S., Wang, W., Sun, Y., Zhao, E., Vatan, L., Szeliga, W., Kotarski, J., Tarkowski, R., Dou, Y., Cho, K., Hensley-Alford, S., Munkarah, A., Liu, R., Zou, W. <strong>Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy.</strong> Nature 527: 249-253, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26503055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26503055</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26503055[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature15520" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26503055">Peng et al. (2015)</a> used human ovarian cancers to demonstrate that EZH2-mediated histone H3 lysine-27 trimethylation (H3K27me3) and DNMT1 (<a href="/entry/126375">126375</a>)-mediated DNA methylation repress the tumor production of TH1-type chemokines CXCL9 (<a href="/entry/601704">601704</a>) and CXCL10 (<a href="/entry/147310">147310</a>), and subsequently determine effector T-cell trafficking to the tumor microenvironment. Treatment with epigenetic modulators removes the repression and increases effector T-cell tumor infiltration, slows down tumor progression, and improves the therapeutic efficacy of PDL1 (PDCD1LG1; <a href="/entry/605402">605402</a>) checkpoint blockade and adoptive T-cell transfusion in tumor-bearing mice. Moreover, tumor EZH2 and DNMT1 are negatively associated with tumor-infiltrating CD8+ T cells and patient outcome. Thus, <a href="#26" class="mim-tip-reference" title="Peng, D., Kryczek, I., Nagarsheth, N., Zhao, L., Wei, S., Wang, W., Sun, Y., Zhao, E., Vatan, L., Szeliga, W., Kotarski, J., Tarkowski, R., Dou, Y., Cho, K., Hensley-Alford, S., Munkarah, A., Liu, R., Zou, W. <strong>Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy.</strong> Nature 527: 249-253, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26503055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26503055</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26503055[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature15520" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26503055">Peng et al. (2015)</a> concluded that epigenetic silencing of TH1-type chemokines is a novel immune-evasion mechanism of tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26503055" 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 mouse embryonic stem cells (ESCs), <a href="#17" class="mim-tip-reference" title="Maier, V. K., Feeney, C. M., Taylor, J. E., Creech, A. L., Qiao, J. W., Szanto, A., Das, P. P., Chevrier, N., Cifuentes-Rojas, C., Orkin, S. H., Carr, S. A., Jaffe, J. D., Mertins, P., Lee, J. T. <strong>Functional proteomic analysis of repressive histone methyltransferase complexes reveals ZNF518B as a G9A regulator.</strong> Molec. Cell. Proteomics 14: 1435-1446, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25680957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25680957</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25680957[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/mcp.M114.044586" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25680957">Maier et al. (2015)</a> confirmed interaction between 2 major repressive histone methyltransferase complexes, PRC2 and G9a (EHMT2; <a href="/entry/604599">604599</a>)-Glp (EHMT1; <a href="/entry/607001">607001</a>). Moreover, the complexes shared several interaction partners, including Znf518a (<a href="/entry/617733">617733</a>) and Znf518b (<a href="/entry/617734">617734</a>). In vitro, Znf518b interacted directly with G9a and with the 2 alternative PRC2 methyltransferase subunits, Ezh1 and Ezh2. Knockdown of Znf518b in mouse ESCs reduced global H3K9 dimethylation. <a href="#17" class="mim-tip-reference" title="Maier, V. K., Feeney, C. M., Taylor, J. E., Creech, A. L., Qiao, J. W., Szanto, A., Das, P. P., Chevrier, N., Cifuentes-Rojas, C., Orkin, S. H., Carr, S. A., Jaffe, J. D., Mertins, P., Lee, J. T. <strong>Functional proteomic analysis of repressive histone methyltransferase complexes reveals ZNF518B as a G9A regulator.</strong> Molec. Cell. Proteomics 14: 1435-1446, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25680957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25680957</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25680957[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/mcp.M114.044586" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25680957">Maier et al. (2015)</a> concluded that ZNF518B may mediate association between PRC2 and G9A-GLP and regulate G9A-GLP activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25680957" 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>Somatic Mutations</em></strong></p><p>
|
|
<a href="#23" class="mim-tip-reference" title="Nikoloski, G., Langemeijer, S. M. C., Kuiper, R. P., Knops, R., Massop, M., Tonnissen, E. R. L. T. M., van der Heijden, A., Scheele, T. N., Vandenberghe, P., de Witte, T., van der Reijden, B. A., Jansen, J. H. <strong>Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes.</strong> Nature Genet. 42: 665-667, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20601954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20601954</a>] [<a href="https://doi.org/10.1038/ng.620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20601954">Nikoloski et al. (2010)</a> identified heterozygous acquired (somatic) deletions at chromosome 7q36.1 encompassing the EZH2 and CUL1 (<a href="/entry/603134">603134</a>) genes in bone marrow cells derived from 13 of 102 individuals with myelodysplastic syndromes (<a href="/entry/252270">252270</a>). Two additional affected individuals had uniparental disomy (UPD) of this region. Genomic analysis of the remaining allele in 1 patient showed no aberrations in CUL1, but a truncating mutation in EZH2. Further sequencing of the EZH2 gene identified somatic mutations in 8 (26%) of 126 individuals, including the original 102 individuals. Three individuals had biallelic mutations. Collectively, 23% of affected individuals had deletions and/or point mutations in the EZH2 gene, and 40% of these individuals also had defects in the TET2 gene (<a href="/entry/612839">612839</a>). Individuals with defects at chromosome 7q showed significantly worse survival compared to those without these defects. The findings suggested that EZH2 may act as a tumor suppressor gene in some cases, and likely influences epigenetic modifications that may lead to cancer, since EZH2 functions as a histone methyltransferase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20601954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Ernst, T., Chase, A. J., Score, J., Hidalgo-Curtis, C. E., Bryant, C., Jones, A. V., Waghorn, K., Zoi, K., Ross, F. M., Reiter, A., Hochhaus, A., Drexler, H. G., Duncombe, A., Cervantes, F., Oscier, D., Boultwood, J., Grand, F. H., Cross, N. C. <strong>Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.</strong> Nature Genet. 42: 722-726, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20601953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20601953</a>] [<a href="https://doi.org/10.1038/ng.621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20601953">Ernst et al. (2010)</a> found that 9 of 12 individuals with myelodysplastic/myeloproliferative neoplasms and acquired UPD encompassing chromosome 7q36 also had a homozygous EZH2 mutation. Further sequencing of 614 individuals with myeloid disorders revealed 49 monoallelic or biallelic EZH2 mutations in 42 individuals; the mutations were found most commonly in those with myelodysplastic/myeloproliferative neoplasms (27 of 219, 12%) and in those with myelofibrosis (4 of 30, 13%). Several patients had refractory anemia, suggesting that somatic acquisition of these abnormalities may be an early event in the disease process. The mutations identified resulted in premature chain termination or direct abrogation of histone methyltransferase activity, suggesting that EZH2 can act as a tumor suppressor for myeloid malignancies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20601953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Morin, R. D., Johnson, N. A., Severson, T. M., Mungall, A. J., An, J., Goya, R., Paul, J. E., Boyle, M., Woolcock, B. W., Kuchenbauer, F., Yap, D., Humphries, R. K., and 26 others. <strong>Somatic mutations altering EZH2 (tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.</strong> Nature Genet. 42: 181-185, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20081860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20081860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20081860[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.518" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20081860">Morin et al. (2010)</a> identified recurrent somatic mutations affecting the tyr641 residue in exon 15 of the conserved EZH2 SET domain in cases of follicular lymphoma and diffuse large B-cell lymphoma of only the germinal-center B-cell subtype (see <a href="/entry/605027">605027</a>). In vitro functional analysis showed that all 4 tyr641 mutants had an approximately 7-fold reduction in methylation ability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20081860" 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="#18" class="mim-tip-reference" title="Makishima, H., Jankowska, A. M., Tiu, R. V., Szpurka, H., Sugimoto, Y., Hu, Z., Saunthararajah, Y., Guinta, K., Keddache, M. A., Putnam, P., Sekeres, M. A., Moliterno, A. R., List, A. F., McDevitt, M. A., Maciejewski, J. P. <strong>Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies.</strong> Leukemia 24: 1799-1804, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20724984/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20724984</a>] [<a href="https://doi.org/10.1038/leu.2010.167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20724984">Makishima et al. (2010)</a> analyzed the EZH2 gene in 344 patients with myeloid malignancies, of whom 15 had UDP7q, 30 had del(7q), and 299 had no loss of heterozygosity of chromosome 7. They found 4 different EZH2 mutations in 3 (20%) of 15 patients with UDP7q and in 2 (7%) of 30 patients with del(7q); in 1 patient without LOH7q, a heterozygous frameshift mutation was identified. All were somatic mutations located in exon 18 or 19, coding for the SET domain of the EZH2 gene. <a href="#18" class="mim-tip-reference" title="Makishima, H., Jankowska, A. M., Tiu, R. V., Szpurka, H., Sugimoto, Y., Hu, Z., Saunthararajah, Y., Guinta, K., Keddache, M. A., Putnam, P., Sekeres, M. A., Moliterno, A. R., List, A. F., McDevitt, M. A., Maciejewski, J. P. <strong>Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies.</strong> Leukemia 24: 1799-1804, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20724984/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20724984</a>] [<a href="https://doi.org/10.1038/leu.2010.167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20724984">Makishima et al. (2010)</a> noted that alterations at tyr641, previously identified in B-cell lymphoma patients (<a href="#22" class="mim-tip-reference" title="Morin, R. D., Johnson, N. A., Severson, T. M., Mungall, A. J., An, J., Goya, R., Paul, J. E., Boyle, M., Woolcock, B. W., Kuchenbauer, F., Yap, D., Humphries, R. K., and 26 others. <strong>Somatic mutations altering EZH2 (tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.</strong> Nature Genet. 42: 181-185, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20081860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20081860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20081860[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.518" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20081860">Morin et al., 2010</a>), were not found in any of the patients screened. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20724984+20081860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Ntziachristos, P., Tsirigos, A., Van Vlierberghe, P., Nedjic, J., Trimarchi, T., Flaherty, M. S., Ferres-Marco, D., da Ros, V., Tang, Z., Siegle, J., Asp, P., Hadler, M., and 17 others. <strong>Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia.</strong> Nature Med. 18: 296-301, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22237151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22237151</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22237151[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22237151">Ntziachristos et al. (2012)</a> reported the presence of loss-of-function mutations and deletions of the EZH2 and SUZ12 (<a href="/entry/606245">606245</a>) genes, which encode crucial components of PRC2, in 25% of T-ALLs (<a href="/entry/613065">613065</a>). To further study the role of PRC2 in T-ALL, <a href="#24" class="mim-tip-reference" title="Ntziachristos, P., Tsirigos, A., Van Vlierberghe, P., Nedjic, J., Trimarchi, T., Flaherty, M. S., Ferres-Marco, D., da Ros, V., Tang, Z., Siegle, J., Asp, P., Hadler, M., and 17 others. <strong>Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia.</strong> Nature Med. 18: 296-301, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22237151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22237151</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22237151[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22237151">Ntziachristos et al. (2012)</a> used NOTCH1 (<a href="/entry/190198">190198</a>)-dependent mouse models of the disease, as well as human T-ALL samples, and combined locus-specific and global analysis of NOTCH1-driven epigenetic changes. These studies demonstrated that activation of NOTCH1 specifically induces loss of the repressive mark lys27 trimethylation of histone-3 (H3K27me3) by antagonizing the activity of PRC2. <a href="#24" class="mim-tip-reference" title="Ntziachristos, P., Tsirigos, A., Van Vlierberghe, P., Nedjic, J., Trimarchi, T., Flaherty, M. S., Ferres-Marco, D., da Ros, V., Tang, Z., Siegle, J., Asp, P., Hadler, M., and 17 others. <strong>Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia.</strong> Nature Med. 18: 296-301, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22237151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22237151</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22237151[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22237151">Ntziachristos et al. (2012)</a> concluded that their studies suggested a tumor suppressor role for PRC2 in human leukemia and suggested a hitherto unrecognized dynamic interplay between oncogenic NOTCH1 and PRC2 function for the regulation of gene expression and cell transformation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22237151" 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="#20" class="mim-tip-reference" title="McCabe, M. T., Ott, H. M., Ganji, G., Korenchuk, S., Thompson, C., Van Aller, G. S. Liu, Y., Graves, A. P., Pietra, A. D., III, Diaz, E., LaFrance, L. V., Mellinger, M., and 10 others. <strong>EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.</strong> Nature 492: 108-112, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23051747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23051747</a>] [<a href="https://doi.org/10.1038/nature11606" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23051747">McCabe et al. (2012)</a> found that specific, direct inhibition of EZH2 methyltransferase activity may be effective in treating EZH2 mutant lymphomas. GSK126, a potent, highly selective, S-adenosyl-methionine-competitive, small-molecular inhibitor of EZH2 methyltransferase activity, decreased global H3K27me3 levels and reactivated silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant germinal-center B-cell subtype of diffuse large B-cell lymphoma (DLBCL) xenografts in mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23051747" 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>Weaver Syndrome</em></strong></p><p>
|
|
<a href="#14" class="mim-tip-reference" title="Gibson, W. T., Hood, R. L., Zhan, S. H., Bulman, D. E., Fejes, A. P., Moore, R., Mungall, A. J., Eydoux, P., Babul-Hirji, R., An, J., Marra, M. A., FORGE Canada Consortium, Chitayat, D., Boycott, K. M., Weaver, D. D., Jones, S. J. M. <strong>Mutations in EZH2 cause Weaver syndrome.</strong> Am. J. Hum. Genet. 90: 110-118, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22177091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22177091</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22177091[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.11.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22177091">Gibson et al. (2012)</a> performed exome sequencing in 2 unrelated patients with Weaver syndrome (WVS; <a href="/entry/277590">277590</a>) and their 4 unaffected parents. In both patients, heterozygous de novo mutations were identified in the EZH2 gene (Y153del, <a href="#0001">601573.0001</a> and H694Y, <a href="#0002">601573.0002</a>, respectively); the presence of the mutations and their de novo status were confirmed by Sanger sequencing. Sequencing of EZH2 in a third patient with Weaver syndrome revealed heterozygosity for another de novo missense mutation (P132S; <a href="#0003">601573.0003</a>). <a href="#14" class="mim-tip-reference" title="Gibson, W. T., Hood, R. L., Zhan, S. H., Bulman, D. E., Fejes, A. P., Moore, R., Mungall, A. J., Eydoux, P., Babul-Hirji, R., An, J., Marra, M. A., FORGE Canada Consortium, Chitayat, D., Boycott, K. M., Weaver, D. D., Jones, S. J. M. <strong>Mutations in EZH2 cause Weaver syndrome.</strong> Am. J. Hum. Genet. 90: 110-118, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22177091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22177091</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22177091[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.11.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22177091">Gibson et al. (2012)</a> noted that a somatic mutation at his694 had previously been found in chronic myelomonocytic leukemia, as well as mutations in nearby residues at positions 690 and 693 in other hematologic malignancies (<a href="#18" class="mim-tip-reference" title="Makishima, H., Jankowska, A. M., Tiu, R. V., Szpurka, H., Sugimoto, Y., Hu, Z., Saunthararajah, Y., Guinta, K., Keddache, M. A., Putnam, P., Sekeres, M. A., Moliterno, A. R., List, A. F., McDevitt, M. A., Maciejewski, J. P. <strong>Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies.</strong> Leukemia 24: 1799-1804, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20724984/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20724984</a>] [<a href="https://doi.org/10.1038/leu.2010.167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20724984">Makishima et al., 2010</a>). Given that patients with Weaver syndrome had been reported to develop tumors or malignancies, including acute lymphoblastic leukemia, <a href="#14" class="mim-tip-reference" title="Gibson, W. T., Hood, R. L., Zhan, S. H., Bulman, D. E., Fejes, A. P., Moore, R., Mungall, A. J., Eydoux, P., Babul-Hirji, R., An, J., Marra, M. A., FORGE Canada Consortium, Chitayat, D., Boycott, K. M., Weaver, D. D., Jones, S. J. M. <strong>Mutations in EZH2 cause Weaver syndrome.</strong> Am. J. Hum. Genet. 90: 110-118, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22177091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22177091</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22177091[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.11.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22177091">Gibson et al. (2012)</a> suggested that constitutive EZH2 mutations might confer a mild predisposition to malignancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20724984+22177091" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Tatton-Brown, K., Rahman, N. <strong>The NSD1 and EZH2 overgrowth genes, similarities and differences.</strong> Am. J. Med. Genet. 163C: 86-91, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23592277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23592277</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23592277[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/10.1002/ajmg.c.31359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23592277">Tatton-Brown and Rahman (2013)</a> reviewed the similarities and differences between the NSD1 (<a href="/entry/606681">606681</a>) and EZH2 genes, which cause the overgrowth Sotos and Weaver syndromes, respectively. The authors stated that 3 mutations that had been identified somatically in myeloid malignancies had been shown to cause Weaver syndrome when present constitutionally, but that none of the Weaver syndrome patients had as yet developed malignancies. The reason for the divergent phenotypes was unclear. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23592277" 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 4 patients with classic features of Weaver syndrome, <a href="#29" class="mim-tip-reference" title="Tatton-Brown, K., Hanks, S., Ruark, E., Zachariou, A., Del Vecchio Duarte, S., Ramsay, E., Snape, K., Murray, A., Perdeaux, E. R., Seal, S., Loveday, C., Banka, S., and 16 others. <strong>Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.</strong> Oncotarget 2: 1127-33, 2011. Note: Erratum: Oncotarget 9: 36719, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22190405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22190405</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22190405[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/10.18632/oncotarget.385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22190405">Tatton-Brown et al. (2011)</a> identified heterozygous mutations in the EZH2 gene (see, e.g., <a href="#0004">601573.0004</a>-<a href="#0006">601573.0006</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were not present in 7 parental samples available for study, establishing that the mutations were de novo in at least 3 of the patients. <a href="#29" class="mim-tip-reference" title="Tatton-Brown, K., Hanks, S., Ruark, E., Zachariou, A., Del Vecchio Duarte, S., Ramsay, E., Snape, K., Murray, A., Perdeaux, E. R., Seal, S., Loveday, C., Banka, S., and 16 others. <strong>Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.</strong> Oncotarget 2: 1127-33, 2011. Note: Erratum: Oncotarget 9: 36719, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22190405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22190405</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22190405[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/10.18632/oncotarget.385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22190405">Tatton-Brown et al. (2011)</a> noted that the mutations in 2 of these patients (R684C, <a href="#0004">601573.0004</a> and Y733X, <a href="#0005">601573.0005</a>) had also been detected as somatic mutations in CMML and myelofibrosis by <a href="#11" class="mim-tip-reference" title="Ernst, T., Chase, A. J., Score, J., Hidalgo-Curtis, C. E., Bryant, C., Jones, A. V., Waghorn, K., Zoi, K., Ross, F. M., Reiter, A., Hochhaus, A., Drexler, H. G., Duncombe, A., Cervantes, F., Oscier, D., Boultwood, J., Grand, F. H., Cross, N. C. <strong>Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.</strong> Nature Genet. 42: 722-726, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20601953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20601953</a>] [<a href="https://doi.org/10.1038/ng.621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20601953">Ernst et al. (2010)</a>. <a href="#29" class="mim-tip-reference" title="Tatton-Brown, K., Hanks, S., Ruark, E., Zachariou, A., Del Vecchio Duarte, S., Ramsay, E., Snape, K., Murray, A., Perdeaux, E. R., Seal, S., Loveday, C., Banka, S., and 16 others. <strong>Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.</strong> Oncotarget 2: 1127-33, 2011. Note: Erratum: Oncotarget 9: 36719, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22190405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22190405</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22190405[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/10.18632/oncotarget.385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22190405">Tatton-Brown et al. (2011)</a> performed Sanger sequencing of the coding sequence and intron-exon boundaries of the EZH2 gene in an additional 300 patients with a clinical diagnosis of Weaver syndrome or with a nonspecific overgrowth syndrome defined as having height or head circumference at least 2 standard deviations above the mean, together with variable additional phenotypic features. Variants considered to be pathogenic were seen in 15 of the 300 patients, but the phenotype in most of the 15 patients was not stated; 9 of the mutations were de novo, 1 (K156E) was inherited in a family (case 2) with nonspecific overgrowth with full segregation with the phenotype, and 5 had unknown inheritance. Among the 19 patients identified with EZH2 mutations, the most prominent finding was increased height with all being at least 2 SD above the mean and 9 patients being over 4 SD above the mean. The increase in head circumference was less dramatic. Learning disability was frequent, with most in the mild to moderate range and some with no reported learning difficulties. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22190405+20601953" 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 mice, the Ezh2 polycomb group protein is most abundant at sites of embryonic lymphopoiesis. In humans, EZH2 is upregulated in proliferating germinal center B cells. Ezh2-deficient mice suffer early embryonic death (<a href="#25" class="mim-tip-reference" title="O'Carroll, D., Erhardt, S., Pagani, M., Barton, S. C., Surani, M. A., Jenuwein, T. <strong>The polycomb-group gene Ezh2 is required for early mouse development.</strong> Molec. Cell. Biol. 21: 4330-4336, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11390661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11390661</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11390661[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.21.13.4330-4336.2001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11390661">O'Carroll et al., 2001</a>). Using Cre-loxP conditional mutagenesis, <a href="#28" class="mim-tip-reference" title="Su, I., Basavaraj, A., Krutchinsky, A. N., Hobert, O., Ullrich, A., Chait, B. T., Tarakhovsky, A. <strong>Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement.</strong> Nature Immun. 4: 124-131, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496962</a>] [<a href="https://doi.org/10.1038/ni876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12496962">Su et al. (2003)</a> demonstrated that Ezh2 controls B-cell development through the regulation of histone H3 (see <a href="/entry/601128">601128</a>) methylation and immunoglobulin heavy chain (IGH; see <a href="/entry/147100">147100</a>) rearrangement. They proposed that EZH2-dependent histone H3 methylation leads to chromatin modification required for normal IGH rearrangement, which is critical for early B-cell development. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11390661+12496962" 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>Increased expression of Cdkn2a (<a href="/entry/600160">600160</a>), which encodes p16(Ink4a) and p19(Arf) isoforms, limits regeneration of pancreatic beta cells in aging mice. <a href="#5" class="mim-tip-reference" title="Chen, H., Gu, X., Su, I., Bottino, R., Contreras, J. L., Tarakhovsky, A., Kim, S. K. <strong>Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus.</strong> Genes Dev. 23: 975-985, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19390090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19390090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19390090[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/10.1101/gad.1742509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19390090">Chen et al. (2009)</a> showed that Ezh2 repressed Cdkn2a in islet beta cells. Ezh2 levels declined in aging islet beta cells, and this attrition coincided with reduced histone H3 trimethylation at Cdkn2a and increased levels of p16(Ink4a) and p19(Arf). Conditional deletion of beta-cell Ezh2 in juvenile mice also reduced H3 trimethylation at the Cdkn2a locus, leading to precocious increased p16(Ink4a) and p19(Arf) levels. These mutant mice had reduced beta-cell proliferation and mass, hypoinsulinemia, and mild diabetes, phenotypes that could be rescued by germline deletion of Cdkn2a. Destruction of beta cells with streptozotocin in wildtype mice increased Ezh2 expression, accompanied by adaptive beta-cell proliferation and reestablishment of beta-cell mass. In contrast, mutant mice treated similarly failed to regenerate beta cells, resulting in lethal diabetes. <a href="#5" class="mim-tip-reference" title="Chen, H., Gu, X., Su, I., Bottino, R., Contreras, J. L., Tarakhovsky, A., Kim, S. K. <strong>Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus.</strong> Genes Dev. 23: 975-985, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19390090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19390090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19390090[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/10.1101/gad.1742509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19390090">Chen et al. (2009)</a> concluded that EZH2 is required for epigenetic repression of CDKN2A and normal beta-cell expansion, and that failure of beta-cell regeneration leads to diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19390090" 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="Delgado-Olguin, P., Huang, Y., Li, X., Christodoulou, D., Seidman, C. E., Seidman, J. G., Tarakhovsky, A., Bruneau, B. G. <strong>Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis.</strong> Nature Genet. 44: 343-347, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22267199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22267199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22267199[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.1068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22267199">Delgado-Olguin et al. (2012)</a> found that conditional deletion of Ezh2 in mouse anterior heart field resulted in right cardiac hypertrophy and fibrosis after birth. Gene expression profiling of Ezh2-knockout hearts revealed derepression of Six1 (<a href="/entry/601205">601205</a>), with concomitant activation of Six1-dependent skeletal muscle-specific genes. Overexpression of Six1 in cultured neonatal mouse cardiomyocytes resulted in hypertrophy comparable to that induced by the hypertrophic agonist endothelin-1 (EDN1; <a href="/entry/131240">131240</a>). Knockdown of Six1 in Ezh2-knockout hearts completely rescued the cardiac phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22267199" 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>6 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/601573" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=601573[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 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EZH2, 3-BP DEL, NT457
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193921146 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193921146;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=rs193921146" 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=rs193921146" 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=RCV000023117" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023117" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023117</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 30-year-old man (patient 1) with Weaver syndrome (WVS; <a href="/entry/277590">277590</a>), originally reported by <a href="#35" class="mim-tip-reference" title="Weaver, D. D., Graham, C. B., Thomas, I. T., Smith, D. W. <strong>A new overgrowth syndrome with accelerated skeletal maturation, unusual facies, and camptodactyly.</strong> J. Pediat. 84: 547-552, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4366187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4366187</a>] [<a href="https://doi.org/10.1016/s0022-3476(74)80675-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4366187">Weaver et al. (1974)</a>, <a href="#14" class="mim-tip-reference" title="Gibson, W. T., Hood, R. L., Zhan, S. H., Bulman, D. E., Fejes, A. P., Moore, R., Mungall, A. J., Eydoux, P., Babul-Hirji, R., An, J., Marra, M. A., FORGE Canada Consortium, Chitayat, D., Boycott, K. M., Weaver, D. D., Jones, S. J. M. <strong>Mutations in EZH2 cause Weaver syndrome.</strong> Am. J. Hum. Genet. 90: 110-118, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22177091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22177091</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22177091[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.11.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22177091">Gibson et al. (2012)</a> identified heterozygosity for a de novo 3-bp deletion at nucleotide 457 (457_459del) in exon 5 of the EZH2 gene, resulting in deletion of a tyrosine residue at codon 153 (tyr153del). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4366187+22177091" 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 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EZH2, HIS694TYR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193921147 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193921147;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=rs193921147" 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=rs193921147" 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=RCV000023118" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023118" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023118</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 11-year-old girl with Weaver syndrome (WVS; <a href="/entry/277590">277590</a>), <a href="#14" class="mim-tip-reference" title="Gibson, W. T., Hood, R. L., Zhan, S. H., Bulman, D. E., Fejes, A. P., Moore, R., Mungall, A. J., Eydoux, P., Babul-Hirji, R., An, J., Marra, M. A., FORGE Canada Consortium, Chitayat, D., Boycott, K. M., Weaver, D. D., Jones, S. J. M. <strong>Mutations in EZH2 cause Weaver syndrome.</strong> Am. J. Hum. Genet. 90: 110-118, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22177091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22177091</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22177091[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.11.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22177091">Gibson et al. (2012)</a> identified heterozygosity for a de novo 2080C-T transition in exon 18 of the EZH2 gene, resulting in a his694-to-tyr (H694Y) substitution within the knot substructure of the active site of the SET domain, predicted to disrupt binding of the enzymatic cofactor S-adenosyl-L-methionine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22177091" 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 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EZH2, PRO132SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193921148 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193921148;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=rs193921148" 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=rs193921148" 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=RCV000023119" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023119" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023119</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 19-year-old woman with Weaver syndrome (WVS; <a href="/entry/277590">277590</a>), <a href="#14" class="mim-tip-reference" title="Gibson, W. T., Hood, R. L., Zhan, S. H., Bulman, D. E., Fejes, A. P., Moore, R., Mungall, A. J., Eydoux, P., Babul-Hirji, R., An, J., Marra, M. A., FORGE Canada Consortium, Chitayat, D., Boycott, K. M., Weaver, D. D., Jones, S. J. M. <strong>Mutations in EZH2 cause Weaver syndrome.</strong> Am. J. Hum. Genet. 90: 110-118, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22177091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22177091</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22177091[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.11.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22177091">Gibson et al. (2012)</a> identified heterozygosity for a de novo 394C-T transition in exon 5 of the EZH2 gene, resulting in a pro132-to-ser (P132S) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22177091" 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 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EZH2, ARG684CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587783626 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587783626;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=rs587783626" 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=rs587783626" 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=RCV000145975 OR RCV001564091 OR RCV004734701" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000145975, RCV001564091, RCV004734701" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000145975...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (case 10) with classic features of Weaver syndrome (WVS; <a href="/entry/277590">277590</a>), <a href="#29" class="mim-tip-reference" title="Tatton-Brown, K., Hanks, S., Ruark, E., Zachariou, A., Del Vecchio Duarte, S., Ramsay, E., Snape, K., Murray, A., Perdeaux, E. R., Seal, S., Loveday, C., Banka, S., and 16 others. <strong>Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.</strong> Oncotarget 2: 1127-33, 2011. Note: Erratum: Oncotarget 9: 36719, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22190405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22190405</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22190405[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/10.18632/oncotarget.385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22190405">Tatton-Brown et al. (2011)</a> identified a heterozygous c.2050C-T transition in the EZH2 gene, resulting in an arg684-to-cys (R684C) substitution. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The one parent who was available for testing did not have the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22190405" 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 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EZH2, TYR733TER
|
|
</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> rs776312600 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs776312600;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/rs776312600?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=rs776312600" 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=rs776312600" 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=RCV002274861" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002274861" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002274861</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (case 14) with classic features of Weaver syndrome (WVS; <a href="/entry/277590">277590</a>), <a href="#29" class="mim-tip-reference" title="Tatton-Brown, K., Hanks, S., Ruark, E., Zachariou, A., Del Vecchio Duarte, S., Ramsay, E., Snape, K., Murray, A., Perdeaux, E. R., Seal, S., Loveday, C., Banka, S., and 16 others. <strong>Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.</strong> Oncotarget 2: 1127-33, 2011. Note: Erratum: Oncotarget 9: 36719, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22190405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22190405</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22190405[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/10.18632/oncotarget.385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22190405">Tatton-Brown et al. (2011)</a> identified a de novo heterozygous c.2199C-G transversion in the EZH2 gene, resulting in a tyr733-to-ter (Y733X) substitution. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22190405" 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 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
8-BP DUP, NT2204
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2129465354 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2129465354;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=rs2129465354" 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=rs2129465354" 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=RCV002274862" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002274862" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002274862</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (case 16) with classic features of Weaver syndrome (WVS; <a href="/entry/277590">277590</a>), <a href="#29" class="mim-tip-reference" title="Tatton-Brown, K., Hanks, S., Ruark, E., Zachariou, A., Del Vecchio Duarte, S., Ramsay, E., Snape, K., Murray, A., Perdeaux, E. R., Seal, S., Loveday, C., Banka, S., and 16 others. <strong>Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.</strong> Oncotarget 2: 1127-33, 2011. Note: Erratum: Oncotarget 9: 36719, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22190405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22190405</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22190405[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/10.18632/oncotarget.385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22190405">Tatton-Brown et al. (2011)</a> identified a de novo heterozygous 8-bp duplication (c.2204_2211dupAGGCTGAT) in the EZH2 gene, predicted to result in a frameshift and a premature stop codon. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22190405" 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="Cao2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., Zhang, Y.
|
|
<strong>Role of histone H3 lysine 27 methylation in polycomb-group silencing.</strong>
|
|
Science 298: 1039-1043, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351676</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12351676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1076997" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Cardoso2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cardoso, C., Mignon, C., Hetet, G., Grandchamps, B., Fontes, M., Colleaux, L.
|
|
<strong>The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders.</strong>
|
|
Europ. J. Hum. Genet. 8: 174-180, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10780782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10780782</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10780782" 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/sj.ejhg.5200439" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Cardoso1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cardoso, C., Timsit, S., Villard, L., Khrestchatisky, M., Fontes, M., Colleaux, L.
|
|
<strong>Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein.</strong>
|
|
Hum. Molec. Genet. 7: 679-684, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9499421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9499421</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9499421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/7.4.679" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Cha2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cha, T.-L., Zhou, B. P., Xia, W., Wu, Y., Yang, C.-C., Chen, C.-T., Ping, B., Otte, A. P., Hung, M.-C.
|
|
<strong>Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3.</strong>
|
|
Science 310: 306-310, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16224021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16224021</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16224021" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1118947" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Chen2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, H., Gu, X., Su, I., Bottino, R., Contreras, J. L., Tarakhovsky, A., Kim, S. K.
|
|
<strong>Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus.</strong>
|
|
Genes Dev. 23: 975-985, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19390090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19390090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19390090[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=19390090" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.1742509" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Chen1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, H., Rossier, C., Antonarakis, S. E.
|
|
<strong>Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2.</strong>
|
|
Genomics 38: 30-37, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8954776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8954776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8954776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1996.0588" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Chen2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, H., Tu, S., Hsieh, J.-T.
|
|
<strong>Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer.</strong>
|
|
J. Biol. Chem. 280: 22437-22444, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15817459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15817459</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15817459" 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.M501379200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Delgado-Olguin2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Delgado-Olguin, P., Huang, Y., Li, X., Christodoulou, D., Seidman, C. E., Seidman, J. G., Tarakhovsky, A., Bruneau, B. G.
|
|
<strong>Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis.</strong>
|
|
Nature Genet. 44: 343-347, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22267199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22267199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22267199[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=22267199" 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/ng.1068" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Di Meglio2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Di Meglio, T., Kratochwil, C. F., Vilain, N., Loche, A., Vitobello, A., Yonehara, K., Hrycaj, S. M., Roska, B., Peters, A. H. F. M., Eichmann, A., Wellik, D., Ducret, S., Rijli, F. M.
|
|
<strong>Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons.</strong>
|
|
Science 339: 204-207, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23307742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23307742</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23307742[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=23307742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1229326" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Dohner1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dohner, K., Brown, J., Hehmann, U., Hetzel, C., Stewart, J., Lowther, G., Scholl, C., Frohling, S., Cuneo, A., Tsui, L. C., Lichter, P., Scherer, S. W., Dohner, H.
|
|
<strong>Molecular cytogenetic characterization of a critical region in bands 7q35-q36 commonly deleted in malignant myeloid disorders.</strong>
|
|
Blood 92: 4031-4035, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9834205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9834205</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9834205" 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="11" class="mim-anchor"></a>
|
|
<a id="Ernst2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ernst, T., Chase, A. J., Score, J., Hidalgo-Curtis, C. E., Bryant, C., Jones, A. V., Waghorn, K., Zoi, K., Ross, F. M., Reiter, A., Hochhaus, A., Drexler, H. G., Duncombe, A., Cervantes, F., Oscier, D., Boultwood, J., Grand, F. H., Cross, N. C.
|
|
<strong>Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.</strong>
|
|
Nature Genet. 42: 722-726, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20601953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20601953</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20601953" 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/ng.621" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Ezhkova2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ezhkova, E., Pasolli, H. A., Parker, J. S., Stokes, N., Su, I., Hannon, G., Tarakhovsky, A., Fuchs, E.
|
|
<strong>Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells.</strong>
|
|
Cell 136: 1122-1135, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19303854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19303854</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19303854[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=19303854" 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.2008.12.043" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Fillmore2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fillmore, C. M., Xu, C., Desai, P. T., Berry, J. M., Rowbotham, S. P., Lin, Y.-J., Zhang, H., Marquez, V. E., Hammerman, P. S., Wong, K.-K., Kim, C. F.
|
|
<strong>EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors.</strong>
|
|
Nature 520: 239-242, 2015. Note: Erratum: Nature 563: E27, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25629630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25629630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25629630[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=25629630" 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/nature14122" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Gibson2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gibson, W. T., Hood, R. L., Zhan, S. H., Bulman, D. E., Fejes, A. P., Moore, R., Mungall, A. J., Eydoux, P., Babul-Hirji, R., An, J., Marra, M. A., FORGE Canada Consortium, Chitayat, D., Boycott, K. M., Weaver, D. D., Jones, S. J. M.
|
|
<strong>Mutations in EZH2 cause Weaver syndrome.</strong>
|
|
Am. J. Hum. Genet. 90: 110-118, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22177091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22177091</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22177091[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=22177091" 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.ajhg.2011.11.018" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Kamminga2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kamminga, L. M., Bystrykh, L. V., de Boer, A., Houwer, S., Douma, J., Weersing, E., Dontje, B., de Haan, G.
|
|
<strong>The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion.</strong>
|
|
Blood 107: 2170-2179, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16293602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16293602</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16293602[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=16293602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2005-09-3585" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Laible1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Laible, G., Haynes, A. R., Lebersorger, A., O'Carroll, D., Mattei, M.-G., Denny, P., Brown, S. D. M., Jenuwein, T.
|
|
<strong>The murine polycomb-group genes Ezh1 and Ezh2 map close to Hox gene clusters on mouse chromosomes 11 and 6.</strong>
|
|
Mammalian Genome 10: 311-314, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051331</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051331" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s003359900993" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Maier2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maier, V. K., Feeney, C. M., Taylor, J. E., Creech, A. L., Qiao, J. W., Szanto, A., Das, P. P., Chevrier, N., Cifuentes-Rojas, C., Orkin, S. H., Carr, S. A., Jaffe, J. D., Mertins, P., Lee, J. T.
|
|
<strong>Functional proteomic analysis of repressive histone methyltransferase complexes reveals ZNF518B as a G9A regulator.</strong>
|
|
Molec. Cell. Proteomics 14: 1435-1446, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25680957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25680957</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25680957[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=25680957" 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/mcp.M114.044586" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Makishima2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Makishima, H., Jankowska, A. M., Tiu, R. V., Szpurka, H., Sugimoto, Y., Hu, Z., Saunthararajah, Y., Guinta, K., Keddache, M. A., Putnam, P., Sekeres, M. A., Moliterno, A. R., List, A. F., McDevitt, M. A., Maciejewski, J. P.
|
|
<strong>Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies.</strong>
|
|
Leukemia 24: 1799-1804, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20724984/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20724984</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20724984" 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/leu.2010.167" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Margueron2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Margueron, R., Justin, N., Ohno, K., Sharpe, M. L., Son, J., Drury, W. J., III, Voigt, P., Martin, S. R., Taylor, W. R., De Marco, V., Pirrotta, V., Reinberg, D., Gamblin, S. J.
|
|
<strong>Role of the polycomb protein EED in the propagation of repressive histone marks.</strong>
|
|
Nature 461: 762-767, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19767730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19767730</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19767730[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=19767730" 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/nature08398" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="McCabe2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McCabe, M. T., Ott, H. M., Ganji, G., Korenchuk, S., Thompson, C., Van Aller, G. S. Liu, Y., Graves, A. P., Pietra, A. D., III, Diaz, E., LaFrance, L. V., Mellinger, M., and 10 others.
|
|
<strong>EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.</strong>
|
|
Nature 492: 108-112, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23051747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23051747</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23051747" 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/nature11606" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Min2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Min, J., Zaslavsky, A., Fedele, G., McLaughlin, S. K., Reczek, E. E., De Raedt, T., Guney, I., Strochlic, D. E., MacConaill, L. E., Beroukhim, R., Bronson, R. T., Ryeom, S., Hahn, W. C., Loda, M., Cichowski, K.
|
|
<strong>An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappa-B.</strong>
|
|
Nature Med. 16: 286-294, 2010. Note: Erratum: Nature Med. 30: 1790 only, 2024.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20154697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20154697</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20154697[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=20154697" 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/nm.2100" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Morin2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morin, R. D., Johnson, N. A., Severson, T. M., Mungall, A. J., An, J., Goya, R., Paul, J. E., Boyle, M., Woolcock, B. W., Kuchenbauer, F., Yap, D., Humphries, R. K., and 26 others.
|
|
<strong>Somatic mutations altering EZH2 (tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.</strong>
|
|
Nature Genet. 42: 181-185, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20081860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20081860</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20081860[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=20081860" 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/ng.518" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Nikoloski2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nikoloski, G., Langemeijer, S. M. C., Kuiper, R. P., Knops, R., Massop, M., Tonnissen, E. R. L. T. M., van der Heijden, A., Scheele, T. N., Vandenberghe, P., de Witte, T., van der Reijden, B. A., Jansen, J. H.
|
|
<strong>Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes.</strong>
|
|
Nature Genet. 42: 665-667, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20601954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20601954</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20601954" 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/ng.620" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Ntziachristos2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ntziachristos, P., Tsirigos, A., Van Vlierberghe, P., Nedjic, J., Trimarchi, T., Flaherty, M. S., Ferres-Marco, D., da Ros, V., Tang, Z., Siegle, J., Asp, P., Hadler, M., and 17 others.
|
|
<strong>Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia.</strong>
|
|
Nature Med. 18: 296-301, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22237151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22237151</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22237151[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=22237151" 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/nm.2651" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="O'Carroll2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
O'Carroll, D., Erhardt, S., Pagani, M., Barton, S. C., Surani, M. A., Jenuwein, T.
|
|
<strong>The polycomb-group gene Ezh2 is required for early mouse development.</strong>
|
|
Molec. Cell. Biol. 21: 4330-4336, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11390661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11390661</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11390661[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=11390661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.21.13.4330-4336.2001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Peng2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peng, D., Kryczek, I., Nagarsheth, N., Zhao, L., Wei, S., Wang, W., Sun, Y., Zhao, E., Vatan, L., Szeliga, W., Kotarski, J., Tarkowski, R., Dou, Y., Cho, K., Hensley-Alford, S., Munkarah, A., Liu, R., Zou, W.
|
|
<strong>Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy.</strong>
|
|
Nature 527: 249-253, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26503055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26503055</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26503055[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=26503055" 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/nature15520" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Plath2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Plath, K., Fang, J., Mlynarczyk-Evans, S. K., Cao, R., Worringer, K. A., Wang, H., de la Cruz, C. C., Otte, A. P., Panning, B., Zhang, Y.
|
|
<strong>Role of histone H3 lysine 27 methylation in X inactivation.</strong>
|
|
Science 300: 131-135, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12649488/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12649488</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12649488" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1084274" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Su2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Su, I., Basavaraj, A., Krutchinsky, A. N., Hobert, O., Ullrich, A., Chait, B. T., Tarakhovsky, A.
|
|
<strong>Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement.</strong>
|
|
Nature Immun. 4: 124-131, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12496962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12496962</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12496962" 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/ni876" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Tatton-Brown2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tatton-Brown, K., Hanks, S., Ruark, E., Zachariou, A., Del Vecchio Duarte, S., Ramsay, E., Snape, K., Murray, A., Perdeaux, E. R., Seal, S., Loveday, C., Banka, S., and 16 others.
|
|
<strong>Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.</strong>
|
|
Oncotarget 2: 1127-33, 2011. Note: Erratum: Oncotarget 9: 36719, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22190405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22190405</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22190405[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=22190405" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.18632/oncotarget.385" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Tatton-Brown2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tatton-Brown, K., Rahman, N.
|
|
<strong>The NSD1 and EZH2 overgrowth genes, similarities and differences.</strong>
|
|
Am. J. Med. Genet. 163C: 86-91, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23592277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23592277</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23592277[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=23592277" 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.c.31359" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Terranova2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Terranova,, R., Yokobayashi, S., Stadler, M. B., Otte, A. P., van Lohuizen, M., Orkin, S. H., Peters, A. H. F. M.
|
|
<strong>Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos.</strong>
|
|
Dev. Cell 15: 668-679, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18848501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18848501</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18848501" 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.devcel.2008.08.015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Varambally2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Varambally, S., Cao, Q., Mani, R.-S., Shankar, S., Wang, X., Ateeq, B., Laxman, B., Cao, X., Jing, X., Ramnarayanan, K., Brenner, J. C., Yu, J., Kim, J. H., Han, B., Tan, P., Kumar-Sinha, C., Lonigro, R. J., Palanisamy, N., Maher, C. A., Chinnaiyan, A. M.
|
|
<strong>Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer.</strong>
|
|
Science 322: 1695-1699, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19008416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19008416</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19008416[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=19008416" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1165395" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Varambally2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., Rubin, M. A., Chinnaiyan, A. M.
|
|
<strong>The polycomb group protein EZH2 is involved in progression of prostate cancer.</strong>
|
|
Nature 419: 624-629, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12374981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12374981</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12374981" 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/nature01075" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Vire2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vire, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.-M., Bollen, M., Esteller, M., Di Croce, L., de Launoit, Y., Fuks, F.
|
|
<strong>The polycomb group protein EZH2 directly controls DNA methylation.</strong>
|
|
Nature 439: 871-874, 2006. Note: Erratum: Nature 446: 824 only, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16357870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16357870</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16357870" 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/nature04431" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Weaver1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weaver, D. D., Graham, C. B., Thomas, I. T., Smith, D. W.
|
|
<strong>A new overgrowth syndrome with accelerated skeletal maturation, unusual facies, and camptodactyly.</strong>
|
|
J. Pediat. 84: 547-552, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4366187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4366187</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4366187" 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/s0022-3476(74)80675-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Xu2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Xu, C.-R., Cole, P. A., Meyers, D. J., Kormish, J., Dent, S., Zaret, K. S.
|
|
<strong>Chromatin 'prepattern' and histone modifiers in a fate choice for liver and pancreas.</strong>
|
|
Science 332: 963-966, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21596989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21596989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21596989[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=21596989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1202845" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Xu2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Xu, K., Wu, Z. J., Groner, A. C., He, H. H., Cai. C., Lis, R. T., Wu, X., Stack, E. C., Loda, M., Liu, T., Xu, H., Cato, L., Thornton, J. E., Gregory, R. I., Morrissey, C., Vessella, R. L., Montironi, R., Magi-Galluzzi, C. Kantoff, P. W., Balk, S. P., Liu, X. S., Brown, M.
|
|
<strong>EZH2 oncogenic activity in castration-resistant prostate cancer cells is polycomb-independent.</strong>
|
|
Science 338: 1465-1469, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23239736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23239736</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23239736[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=23239736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1227604" 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">
|
|
Sonja A. Rasmussen - updated : 08/11/2022
|
|
</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">
|
|
Patricia A. Hartz - updated : 10/18/2017<br>Ada Hamosh - updated : 02/22/2016<br>Ada Hamosh - updated : 7/6/2015<br>Marla J. F. O'Neill - updated : 5/2/2013<br>Ada Hamosh - updated : 1/29/2013<br>Ada Hamosh - updated : 1/14/2013<br>Ada Hamosh - updated : 1/7/2013<br>Patricia A. Hartz - updated : 3/19/2012<br>Ada Hamosh - updated : 3/13/2012<br>Marla J. F. O'Neill - updated : 1/10/2012<br>Ada Hamosh - updated : 6/6/2011<br>Cassandra L. Kniffin - updated : 11/18/2010<br>Patricia A. Hartz - updated : 11/15/2010<br>Patricia A. Hartz - updated : 5/18/2010<br>Ada Hamosh - updated : 11/5/2009<br>Patricia A. Hartz - updated : 9/21/2009<br>Patricia A. Hartz - updated : 3/18/2009<br>Ada Hamosh - updated : 12/29/2008<br>Victor A. McKusick - updated : 2/23/2007<br>Ada Hamosh - updated : 12/6/2006<br>Ada Hamosh - updated : 10/25/2005<br>Ada Hamosh - updated : 4/15/2003<br>Paul J. Converse - updated : 1/23/2003<br>Ada Hamosh - updated : 11/13/2002<br>Ada Hamosh - updated : 10/18/2002<br>Victor A. McKusick - updated : 11/1/2000<br>Carol A. Bocchini - updated : 6/15/1999
|
|
</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 : 12/13/1996
|
|
</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 : 07/01/2024
|
|
</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">
|
|
alopez : 04/12/2024<br>carol : 08/12/2022<br>carol : 08/11/2022<br>carol : 12/16/2019<br>carol : 10/10/2019<br>alopez : 03/28/2019<br>carol : 11/14/2017<br>ckniffin : 11/10/2017<br>mgross : 10/18/2017<br>alopez : 02/22/2016<br>alopez : 7/6/2015<br>alopez : 7/6/2015<br>carol : 5/2/2013<br>mgross : 2/5/2013<br>alopez : 1/31/2013<br>terry : 1/29/2013<br>alopez : 1/15/2013<br>terry : 1/14/2013<br>alopez : 1/7/2013<br>terry : 1/7/2013<br>mgross : 3/19/2012<br>terry : 3/19/2012<br>alopez : 3/15/2012<br>terry : 3/13/2012<br>terry : 1/20/2012<br>carol : 1/10/2012<br>alopez : 6/13/2011<br>terry : 6/6/2011<br>wwang : 11/23/2010<br>ckniffin : 11/18/2010<br>mgross : 11/16/2010<br>terry : 11/15/2010<br>mgross : 5/19/2010<br>mgross : 5/18/2010<br>terry : 5/18/2010<br>alopez : 11/9/2009<br>alopez : 11/9/2009<br>terry : 11/5/2009<br>mgross : 10/2/2009<br>terry : 9/21/2009<br>mgross : 3/18/2009<br>terry : 3/18/2009<br>alopez : 12/30/2008<br>alopez : 12/29/2008<br>terry : 12/29/2008<br>terry : 5/9/2007<br>alopez : 4/27/2007<br>alopez : 3/2/2007<br>terry : 2/23/2007<br>alopez : 12/20/2006<br>alopez : 12/20/2006<br>terry : 12/6/2006<br>alopez : 10/26/2005<br>alopez : 10/26/2005<br>terry : 10/25/2005<br>terry : 5/15/2003<br>alopez : 4/17/2003<br>terry : 4/15/2003<br>alopez : 1/31/2003<br>mgross : 1/23/2003<br>alopez : 11/14/2002<br>terry : 11/13/2002<br>alopez : 10/21/2002<br>alopez : 10/21/2002<br>terry : 10/18/2002<br>mgross : 6/4/2001<br>terry : 1/18/2001<br>mcapotos : 11/9/2000<br>mcapotos : 11/9/2000<br>mcapotos : 11/8/2000<br>mcapotos : 11/7/2000<br>terry : 11/1/2000<br>carol : 6/15/1999<br>alopez : 8/6/1998<br>alopez : 6/23/1998<br>terry : 2/4/1997<br>mark : 12/16/1996
|
|
</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> 601573
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ENHANCER OF ZESTE 2 POLYCOMB REPRESSIVE COMPLEX 2 SUBUNIT; EZH2
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
ENHANCER OF ZESTE, DROSOPHILA, HOMOLOG 2<br />
|
|
ENX1
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: EZH2</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 63119004;
|
|
|
|
|
|
<strong>ICD10CM:</strong> Q87.3;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 7q36.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 7:148,807,383-148,884,291 </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="1">
|
|
<span class="mim-font">
|
|
7q36.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Weaver syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
277590
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</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>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The EZH2 gene encodes a histone methyltransferase that constitute the catalytic component of the polycomb repressive complex-2 (PRC2), which functions to initiate epigenetic silencing of genes involved in cell fate decisions. EZH2 specifically methylates nucleosomal histone H3 (see 602810) at lysine-27 (H3-K27) (summary by Cao et al., 2002 and Ernst et al., 2010). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>To identify genes that map on human chromosome 21 that may contribute to the phenotype of Down syndrome, Chen et al. (1996) applied exon trapping to cosmid DNA from a chromosome 21-specific library. One of the potential exons that was cloned and partially characterized showed strong homology to the Drosophila 'enhancer of zeste' protein from amino acid 665 to amino acid 694. The Drosophila protein is a member of the Polycomb group, which maintains homeotic gene repression and is thought to control gene expression by regulating chromatin. Chen et al. (1996) cloned the full-length cDNA for this human homolog, termed EZH2. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Cardoso et al. (2000) reported the characteristics of all 20 exons of the EZH2 gene and the adjoining splice donor and splice acceptor sites and gave the size of the 19 introns. Transcription began near the beginning of exon 2. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Chen et al. (1996) mapped the human EZH2 cDNA within YACs between marker D21S65 and ERG (165080) on 21q22.2. However, Cardoso et al. (2000) later showed by FISH that the functional EZH2 gene maps to 7q35, not 21q22, and that the sequence isolated from the chromosome 21 cosmid corresponds to a pseudogene. </p><p>By FISH, Laible et al. (1999) mapped the mouse Ezh2 gene to chromosome 6. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Several lines of evidence suggested a critical role for the EZH2 protein during normal and perturbed development of the hematopoietic and central nervous systems. Indeed, the EZH2 protein has been shown to associate with the VAV1 protooncoprotein (164875) and with the XNP protein (300032), the product of a gene associated with mental retardation (Cardoso et al., 1998). </p><p>The nature of the EZH2 protein and its mapping to the critical region for malignant myeloid disorders led Cardoso et al. (2000) to propose that the EZH2 gene is involved in the pathogenesis of 7q35-q36 aberrations in myeloid leukemia (Dohner et al., 1998). </p><p>Varambally et al. (2002) demonstrated through gene expression profiling that EZH2 is overexpressed in hormone-refractory, metastatic prostate cancer (see 176807). Small interfering RNA (siRNA) duplexes targeted against EZH2 reduced the amounts of EZH2 protein present in prostate cells and also inhibited cell proliferation in vitro. Ectopic expression of EZH2 in prostate cells induced transcriptional repression of a specific cohort of genes. Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity. Amounts of both EZH2 mRNA and EZH2 protein were increased in metastatic prostate cancer. In addition, clinically localized prostate cancers that expressed higher concentrations of EZH2 showed a poorer prognosis. Thus, Varambally et al. (2002) concluded that dysregulated expression of EZH2 may be involved in the progression of prostate cancer as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression. </p><p>Cao et al. (2002) reported the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. Cao et al. (2002) demonstrated that the complex specifically methylates nucleosomal histone H3 (see 601128) at lysine-27 (H3-K27). Using chromatin immunoprecipitation assays, Cao et al. (2002) showed that H3-K27 methylation colocalizes with, and is dependent on, E(Z) binding at an 'Ultrabithorax' (Ubx) Polycomb response element, and that this methylation correlates with Ubx expression. Methylation on H3-K27 facilitates binding of Polycomb, a component of the Polycomb repressive complex 1 (PRC1 complex), to the histone H3 N-terminal tail. Thus, Cao et al. (2002) concluded that their studies established a link between histone methylation and Polycomb group-mediated gene silencing. The complex responsible for histone methyltransferase activity included EZH2, SUZ12 (606245), and EED (605984). EZH2 contains a SET domain, a signature motif for all known histone lysine methyltransferases except the H3-K79 methyltransferase DOT1, and is therefore likely to be the catalytic subunit. </p><p>Plath et al. (2003) demonstrated that transient recruitment of the EED-EZH2 complex to the inactive X chromosome occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the inactive X depend on Xist (314670) RNA but are independent of its silencing function. Plath et al. (2003) concluded that taken together, their results suggest a role for EED-EZH2-mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the inactive X. </p><p>Cha et al. (2005) showed that AKT (164730) phosphorylates EZH2 at serine-21 and suppresses its methyltransferase activity by impeding EZH2 binding to histone H3, which results in a decrease of lysine-27 trimethylation and derepression of silenced genes. Cha et al. (2005) concluded that their results imply that AKT regulates the methylation activity, through phosphorylation of EZH2, which may contribute to oncogenesis. </p><p>Vire et al. (2006) showed that the silencing pathways of the polycomb group (PcG) and DNA methyltransferases systems are mechanically linked. They found that the PcG protein EZH2 interacts--within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3)--with DNA methyltransferases DNMT1 (126375), DNMT3A (602769), and DNMT3B (602900) and associates with DNMT activity in vivo. Chromatin immunoprecipitations indicated that binding of DNMTs to several EZH2-repressed genes depends on the presence of EZH2. Furthermore, Vire et al. (2006) showed by bisulfite genomic sequencing that EZH2 is required for DNA methylation of EZH2-target promoters. Vire et al. (2006) concluded that their results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between 2 key epigenetic repression systems. </p><p>As indicated by the work of Kamminga et al. (2006), EZH2 is, like latexin (LXN; 609305), a stem cell regulator. </p><p>Varambally et al. (2008) demonstrated that the expression and function of EZH2 in cancer cell lines are inhibited by microRNA 101 (MIRN101; see 612511). Analysis of human prostate tumors revealed that MIRN101 expression decreases during cancer progression, paralleling an increase in EZH2 expression. One or both of the 2 genomic loci encoding MIRN101 were somatically lost in 37.5% of clinically localized prostate cancer (see 176807) cells (6 of 16) and 66.7% of metastatic disease cells (22 of 33). Varambally et al. (2008) proposed that the genomic loss of MIRN101 in cancer leads to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways, resulting in cancer progression. </p><p>Terranova et al. (2008) found that mouse Ezh2 and Rnf2 (608985) were independently required for genomic contraction and repression of imprinted genes during early embryonic development. </p><p>The gene silencing activity of the Polycomb repressive complex-2 (PRC2; see 601674) depends on its ability to trimethylate lys27 of histone 3 (H3K27) by the catalytic SET domain of the EZH2 subunit and at least 2 other subunits of the complex: SUZ12 (606245) and EED (605984). Margueron et al. (2009) showed that the carboxy-terminal domain of EED specifically binds to histone tails carrying trimethyl-lysine residues associated with repressive chromatin marks, and that this leads to the allosteric activation of the methyltransferase activity of PRC2. Mutations in EED that prevent it from recognizing repressive trimethyl-lysine marks abolished the activation of PRC2 in vitro and, in Drosophila, reduced global methylation and disrupted development. Margueron et al. (2009) concluded that their findings suggested a model for the propagation of the H3K27 methyl-3 mark that accounts for the maintenance of repressive chromatin domains and for the transmission of a histone modification from mother to daughter cells. </p><p>Chen et al. (2005) showed that increased EZH2 expression in normal human prostate epithelial cells suppressed DAB2IP (609205) gene expression. In contrast, knockdown of endogenous EZH2 levels in prostate cancer cells via siRNA increased DAB2IP expression. In prostate cancer, but not normal prostate epithelial cells, an EZH2 complex that included EED and SUZ12 associated with the DAB2IP promoter and increased promoter occupancy by methylated H3K27 and HDAC1 (601241). Knockdown of EZH2 reduced the association of methylated H3K27 and HDAC1 with the DAB2IP promoter. Chen et al. (2005) concluded that DAB2IP is a target for EZH2-mediated gene silencing in prostate epithelium. </p><p>Ezhkova et al. (2009) found that expression of Ezh2 in mouse epidermal progenitor cells diminished concomitant with their embryonic differentiation and postnatal decline in proliferative activity. Conditional knockout of Ezh2 in basal keratinocytes resulted in thickened stratum corneum and granular layer and precocious acquisition of epidermal barrier function in the embryo. Molecularly, these changes correlated with global reduction of H3K27 trimethylation marks and specifically with derepression of a 2-Mb epidermal differentiation complex controlled by Ink4a (CDKN2A; 600160)/Ink4b (CDKN2B; 600431). Reduced histone modification at this locus permitted recruitment of the AP1 transcription factor (see 165160) and expression of genes associated with epidermal differentiation. </p><p>Using predominantly a mouse tumor model and genetic manipulation of human prostate cancer cells, Min et al. (2010) showed that direct EZH2-mediated downregulation of DAB2IP induced an epithelial-to-mesenchymal transition (EMT) in the cancer cells and increased their metastatic potential. DAB2IP downregulation activated RAS (HRAS; 190020) and NFKB (see 164011). RAS activation drove cell growth, while NFKB activation triggered EMT and metastasis. Min et al. (2010) found an inverse relationship between EZH2 and DAB2IP expression in human prostate cancer tissues and an inverse relationship between DAB2IP expression and tumor grade. Min et al. (2010) concluded that epigenetic suppression of DAB2IP by EZH2 is a major mechanism of DAB2IP inactivation in human prostate cancer and increases metastatic potential. </p><p>Xu et al. (2011) isolated mouse embryonic endoderm cells and assessed histone modifications at regulatory elements of silent genes that are activated upon liver or pancreas fate choices, and found that the liver and pancreas elements have distinct chromatin patterns. Furthermore, the histone acetyltransferase P300 (602700), recruited via bone morphogenetic protein (BMP; see 600799) signaling, and the histone methyltransferase Ezh2 have modulatory roles in the fate choice. Xu et al. (2011) concluded that their studies revealed a functional 'prepattern' of chromatin states within multipotent progenitors and potential targets to modulate cell fate induction. </p><p>Xu et al. (2012) found that the oncogenic function of EZH2 in cells of castration-resistant prostate cancer (see 176807) is independent of its role as a transcriptional repressor. Instead, it involves the ability of EZH2 to act as a coactivator for critical transcription factors including the androgen receptor (313700). This functional switch is dependent on phosphorylation of EZH2 and requires an intact methyltransferase domain. </p><p>Di Meglio et al. (2013) investigated the role of histone methyltransferase Ezh2 in tangential migration of mouse precerebellar pontine nuclei, the main relay between neocortex and cerebellum. By counteracting the sonic hedgehog (see 600725) pathway, Ezh2 represses netrin-1 (601614) in dorsal hindbrain, which allows normal pontine neuron migration. In Ezh2 mutants, ectopic netrin-1 derepression resulted in abnormal migration and supernumerary nuclei integrating in brain circuitry. Moreover, intrinsic topographic organization of pontine nuclei according to rostrocaudal progenitor origin was maintained throughout migration and correlated with patterned cortical input. Ezh2 maintains spatially restricted Hox expression, which, in turn, regulates differential expression of the repulsive receptor Unc5b (607870) in migrating neurons; together, they generate subsets with distinct responsiveness to environmental netrin-1. Thus, Di Meglio et al. (2013) concluded that Ezh2-dependent epigenetic regulation of intrinsic and extrinsic transcriptional programs controls topographic neuronal guidance and connectivity in the cortico-ponto-cerebellar pathway. </p><p>Fillmore et al. (2015) demonstrated that EZH2 inhibition has differential effects on the TopoII inhibitor response of nonsmall-cell lung cancers in vitro and in vivo. EGFR (131550) and BRG1 (603254) mutations are genetic biomarkers that predict enhanced sensitivity to TopoII inhibitor in response to EZH2 inhibition. BRG1 loss-of-function mutant tumors respond to EZH2 inhibition with increased S phase, anaphase bridging, apoptosis, and TopoII inhibitor sensitivity. Conversely, EGFR and BRG1 wildtype tumors upregulate BRG1 in response to EZH2 inhibition and ultimately become more resistant to TopoII inhibitor. EGFR gain-of-function mutant tumors are also sensitive to dual EZH2 inhibition and TopoII inhibitor, because of genetic antagonism between EGFR and BRG1. </p><p>Peng et al. (2015) used human ovarian cancers to demonstrate that EZH2-mediated histone H3 lysine-27 trimethylation (H3K27me3) and DNMT1 (126375)-mediated DNA methylation repress the tumor production of TH1-type chemokines CXCL9 (601704) and CXCL10 (147310), and subsequently determine effector T-cell trafficking to the tumor microenvironment. Treatment with epigenetic modulators removes the repression and increases effector T-cell tumor infiltration, slows down tumor progression, and improves the therapeutic efficacy of PDL1 (PDCD1LG1; 605402) checkpoint blockade and adoptive T-cell transfusion in tumor-bearing mice. Moreover, tumor EZH2 and DNMT1 are negatively associated with tumor-infiltrating CD8+ T cells and patient outcome. Thus, Peng et al. (2015) concluded that epigenetic silencing of TH1-type chemokines is a novel immune-evasion mechanism of tumors. </p><p>Using mouse embryonic stem cells (ESCs), Maier et al. (2015) confirmed interaction between 2 major repressive histone methyltransferase complexes, PRC2 and G9a (EHMT2; 604599)-Glp (EHMT1; 607001). Moreover, the complexes shared several interaction partners, including Znf518a (617733) and Znf518b (617734). In vitro, Znf518b interacted directly with G9a and with the 2 alternative PRC2 methyltransferase subunits, Ezh1 and Ezh2. Knockdown of Znf518b in mouse ESCs reduced global H3K9 dimethylation. Maier et al. (2015) concluded that ZNF518B may mediate association between PRC2 and G9A-GLP and regulate G9A-GLP activity. </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>Somatic Mutations</em></strong></p><p>
|
|
Nikoloski et al. (2010) identified heterozygous acquired (somatic) deletions at chromosome 7q36.1 encompassing the EZH2 and CUL1 (603134) genes in bone marrow cells derived from 13 of 102 individuals with myelodysplastic syndromes (252270). Two additional affected individuals had uniparental disomy (UPD) of this region. Genomic analysis of the remaining allele in 1 patient showed no aberrations in CUL1, but a truncating mutation in EZH2. Further sequencing of the EZH2 gene identified somatic mutations in 8 (26%) of 126 individuals, including the original 102 individuals. Three individuals had biallelic mutations. Collectively, 23% of affected individuals had deletions and/or point mutations in the EZH2 gene, and 40% of these individuals also had defects in the TET2 gene (612839). Individuals with defects at chromosome 7q showed significantly worse survival compared to those without these defects. The findings suggested that EZH2 may act as a tumor suppressor gene in some cases, and likely influences epigenetic modifications that may lead to cancer, since EZH2 functions as a histone methyltransferase. </p><p>Ernst et al. (2010) found that 9 of 12 individuals with myelodysplastic/myeloproliferative neoplasms and acquired UPD encompassing chromosome 7q36 also had a homozygous EZH2 mutation. Further sequencing of 614 individuals with myeloid disorders revealed 49 monoallelic or biallelic EZH2 mutations in 42 individuals; the mutations were found most commonly in those with myelodysplastic/myeloproliferative neoplasms (27 of 219, 12%) and in those with myelofibrosis (4 of 30, 13%). Several patients had refractory anemia, suggesting that somatic acquisition of these abnormalities may be an early event in the disease process. The mutations identified resulted in premature chain termination or direct abrogation of histone methyltransferase activity, suggesting that EZH2 can act as a tumor suppressor for myeloid malignancies. </p><p>Morin et al. (2010) identified recurrent somatic mutations affecting the tyr641 residue in exon 15 of the conserved EZH2 SET domain in cases of follicular lymphoma and diffuse large B-cell lymphoma of only the germinal-center B-cell subtype (see 605027). In vitro functional analysis showed that all 4 tyr641 mutants had an approximately 7-fold reduction in methylation ability. </p><p>Makishima et al. (2010) analyzed the EZH2 gene in 344 patients with myeloid malignancies, of whom 15 had UDP7q, 30 had del(7q), and 299 had no loss of heterozygosity of chromosome 7. They found 4 different EZH2 mutations in 3 (20%) of 15 patients with UDP7q and in 2 (7%) of 30 patients with del(7q); in 1 patient without LOH7q, a heterozygous frameshift mutation was identified. All were somatic mutations located in exon 18 or 19, coding for the SET domain of the EZH2 gene. Makishima et al. (2010) noted that alterations at tyr641, previously identified in B-cell lymphoma patients (Morin et al., 2010), were not found in any of the patients screened. </p><p>Ntziachristos et al. (2012) reported the presence of loss-of-function mutations and deletions of the EZH2 and SUZ12 (606245) genes, which encode crucial components of PRC2, in 25% of T-ALLs (613065). To further study the role of PRC2 in T-ALL, Ntziachristos et al. (2012) used NOTCH1 (190198)-dependent mouse models of the disease, as well as human T-ALL samples, and combined locus-specific and global analysis of NOTCH1-driven epigenetic changes. These studies demonstrated that activation of NOTCH1 specifically induces loss of the repressive mark lys27 trimethylation of histone-3 (H3K27me3) by antagonizing the activity of PRC2. Ntziachristos et al. (2012) concluded that their studies suggested a tumor suppressor role for PRC2 in human leukemia and suggested a hitherto unrecognized dynamic interplay between oncogenic NOTCH1 and PRC2 function for the regulation of gene expression and cell transformation. </p><p>McCabe et al. (2012) found that specific, direct inhibition of EZH2 methyltransferase activity may be effective in treating EZH2 mutant lymphomas. GSK126, a potent, highly selective, S-adenosyl-methionine-competitive, small-molecular inhibitor of EZH2 methyltransferase activity, decreased global H3K27me3 levels and reactivated silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant germinal-center B-cell subtype of diffuse large B-cell lymphoma (DLBCL) xenografts in mice. </p><p><strong><em>Weaver Syndrome</em></strong></p><p>
|
|
Gibson et al. (2012) performed exome sequencing in 2 unrelated patients with Weaver syndrome (WVS; 277590) and their 4 unaffected parents. In both patients, heterozygous de novo mutations were identified in the EZH2 gene (Y153del, 601573.0001 and H694Y, 601573.0002, respectively); the presence of the mutations and their de novo status were confirmed by Sanger sequencing. Sequencing of EZH2 in a third patient with Weaver syndrome revealed heterozygosity for another de novo missense mutation (P132S; 601573.0003). Gibson et al. (2012) noted that a somatic mutation at his694 had previously been found in chronic myelomonocytic leukemia, as well as mutations in nearby residues at positions 690 and 693 in other hematologic malignancies (Makishima et al., 2010). Given that patients with Weaver syndrome had been reported to develop tumors or malignancies, including acute lymphoblastic leukemia, Gibson et al. (2012) suggested that constitutive EZH2 mutations might confer a mild predisposition to malignancy. </p><p>Tatton-Brown and Rahman (2013) reviewed the similarities and differences between the NSD1 (606681) and EZH2 genes, which cause the overgrowth Sotos and Weaver syndromes, respectively. The authors stated that 3 mutations that had been identified somatically in myeloid malignancies had been shown to cause Weaver syndrome when present constitutionally, but that none of the Weaver syndrome patients had as yet developed malignancies. The reason for the divergent phenotypes was unclear. </p><p>In 4 patients with classic features of Weaver syndrome, Tatton-Brown et al. (2011) identified heterozygous mutations in the EZH2 gene (see, e.g., 601573.0004-601573.0006). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were not present in 7 parental samples available for study, establishing that the mutations were de novo in at least 3 of the patients. Tatton-Brown et al. (2011) noted that the mutations in 2 of these patients (R684C, 601573.0004 and Y733X, 601573.0005) had also been detected as somatic mutations in CMML and myelofibrosis by Ernst et al. (2010). Tatton-Brown et al. (2011) performed Sanger sequencing of the coding sequence and intron-exon boundaries of the EZH2 gene in an additional 300 patients with a clinical diagnosis of Weaver syndrome or with a nonspecific overgrowth syndrome defined as having height or head circumference at least 2 standard deviations above the mean, together with variable additional phenotypic features. Variants considered to be pathogenic were seen in 15 of the 300 patients, but the phenotype in most of the 15 patients was not stated; 9 of the mutations were de novo, 1 (K156E) was inherited in a family (case 2) with nonspecific overgrowth with full segregation with the phenotype, and 5 had unknown inheritance. Among the 19 patients identified with EZH2 mutations, the most prominent finding was increased height with all being at least 2 SD above the mean and 9 patients being over 4 SD above the mean. The increase in head circumference was less dramatic. Learning disability was frequent, with most in the mild to moderate range and some with no reported learning difficulties. </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 mice, the Ezh2 polycomb group protein is most abundant at sites of embryonic lymphopoiesis. In humans, EZH2 is upregulated in proliferating germinal center B cells. Ezh2-deficient mice suffer early embryonic death (O'Carroll et al., 2001). Using Cre-loxP conditional mutagenesis, Su et al. (2003) demonstrated that Ezh2 controls B-cell development through the regulation of histone H3 (see 601128) methylation and immunoglobulin heavy chain (IGH; see 147100) rearrangement. They proposed that EZH2-dependent histone H3 methylation leads to chromatin modification required for normal IGH rearrangement, which is critical for early B-cell development. </p><p>Increased expression of Cdkn2a (600160), which encodes p16(Ink4a) and p19(Arf) isoforms, limits regeneration of pancreatic beta cells in aging mice. Chen et al. (2009) showed that Ezh2 repressed Cdkn2a in islet beta cells. Ezh2 levels declined in aging islet beta cells, and this attrition coincided with reduced histone H3 trimethylation at Cdkn2a and increased levels of p16(Ink4a) and p19(Arf). Conditional deletion of beta-cell Ezh2 in juvenile mice also reduced H3 trimethylation at the Cdkn2a locus, leading to precocious increased p16(Ink4a) and p19(Arf) levels. These mutant mice had reduced beta-cell proliferation and mass, hypoinsulinemia, and mild diabetes, phenotypes that could be rescued by germline deletion of Cdkn2a. Destruction of beta cells with streptozotocin in wildtype mice increased Ezh2 expression, accompanied by adaptive beta-cell proliferation and reestablishment of beta-cell mass. In contrast, mutant mice treated similarly failed to regenerate beta cells, resulting in lethal diabetes. Chen et al. (2009) concluded that EZH2 is required for epigenetic repression of CDKN2A and normal beta-cell expansion, and that failure of beta-cell regeneration leads to diabetes. </p><p>Delgado-Olguin et al. (2012) found that conditional deletion of Ezh2 in mouse anterior heart field resulted in right cardiac hypertrophy and fibrosis after birth. Gene expression profiling of Ezh2-knockout hearts revealed derepression of Six1 (601205), with concomitant activation of Six1-dependent skeletal muscle-specific genes. Overexpression of Six1 in cultured neonatal mouse cardiomyocytes resulted in hypertrophy comparable to that induced by the hypertrophic agonist endothelin-1 (EDN1; 131240). Knockdown of Six1 in Ezh2-knockout hearts completely rescued the cardiac phenotype. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>6 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EZH2, 3-BP DEL, NT457
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193921146,
|
|
|
|
|
|
|
|
ClinVar: RCV000023117
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 30-year-old man (patient 1) with Weaver syndrome (WVS; 277590), originally reported by Weaver et al. (1974), Gibson et al. (2012) identified heterozygosity for a de novo 3-bp deletion at nucleotide 457 (457_459del) in exon 5 of the EZH2 gene, resulting in deletion of a tyrosine residue at codon 153 (tyr153del). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EZH2, HIS694TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193921147,
|
|
|
|
|
|
|
|
ClinVar: RCV000023118
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 11-year-old girl with Weaver syndrome (WVS; 277590), Gibson et al. (2012) identified heterozygosity for a de novo 2080C-T transition in exon 18 of the EZH2 gene, resulting in a his694-to-tyr (H694Y) substitution within the knot substructure of the active site of the SET domain, predicted to disrupt binding of the enzymatic cofactor S-adenosyl-L-methionine. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EZH2, PRO132SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193921148,
|
|
|
|
|
|
|
|
ClinVar: RCV000023119
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 19-year-old woman with Weaver syndrome (WVS; 277590), Gibson et al. (2012) identified heterozygosity for a de novo 394C-T transition in exon 5 of the EZH2 gene, resulting in a pro132-to-ser (P132S) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EZH2, ARG684CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587783626,
|
|
|
|
|
|
|
|
ClinVar: RCV000145975, RCV001564091, RCV004734701
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (case 10) with classic features of Weaver syndrome (WVS; 277590), Tatton-Brown et al. (2011) identified a heterozygous c.2050C-T transition in the EZH2 gene, resulting in an arg684-to-cys (R684C) substitution. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The one parent who was available for testing did not have the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EZH2, TYR733TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs776312600,
|
|
|
|
|
|
gnomAD: rs776312600,
|
|
|
|
|
|
ClinVar: RCV002274861
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (case 14) with classic features of Weaver syndrome (WVS; 277590), Tatton-Brown et al. (2011) identified a de novo heterozygous c.2199C-G transversion in the EZH2 gene, resulting in a tyr733-to-ter (Y733X) substitution. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 WEAVER SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
8-BP DUP, NT2204
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2129465354,
|
|
|
|
|
|
|
|
ClinVar: RCV002274862
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (case 16) with classic features of Weaver syndrome (WVS; 277590), Tatton-Brown et al. (2011) identified a de novo heterozygous 8-bp duplication (c.2204_2211dupAGGCTGAT) in the EZH2 gene, predicted to result in a frameshift and a premature stop codon. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. </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">
|
|
Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., Zhang, Y.
|
|
<strong>Role of histone H3 lysine 27 methylation in polycomb-group silencing.</strong>
|
|
Science 298: 1039-1043, 2002.
|
|
|
|
|
|
[PubMed: 12351676]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1076997]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cardoso, C., Mignon, C., Hetet, G., Grandchamps, B., Fontes, M., Colleaux, L.
|
|
<strong>The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders.</strong>
|
|
Europ. J. Hum. Genet. 8: 174-180, 2000.
|
|
|
|
|
|
[PubMed: 10780782]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200439]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cardoso, C., Timsit, S., Villard, L., Khrestchatisky, M., Fontes, M., Colleaux, L.
|
|
<strong>Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein.</strong>
|
|
Hum. Molec. Genet. 7: 679-684, 1998.
|
|
|
|
|
|
[PubMed: 9499421]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/7.4.679]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cha, T.-L., Zhou, B. P., Xia, W., Wu, Y., Yang, C.-C., Chen, C.-T., Ping, B., Otte, A. P., Hung, M.-C.
|
|
<strong>Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3.</strong>
|
|
Science 310: 306-310, 2005.
|
|
|
|
|
|
[PubMed: 16224021]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1118947]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, H., Gu, X., Su, I., Bottino, R., Contreras, J. L., Tarakhovsky, A., Kim, S. K.
|
|
<strong>Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus.</strong>
|
|
Genes Dev. 23: 975-985, 2009.
|
|
|
|
|
|
[PubMed: 19390090]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.1742509]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, H., Rossier, C., Antonarakis, S. E.
|
|
<strong>Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2.</strong>
|
|
Genomics 38: 30-37, 1996.
|
|
|
|
|
|
[PubMed: 8954776]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0588]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, H., Tu, S., Hsieh, J.-T.
|
|
<strong>Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer.</strong>
|
|
J. Biol. Chem. 280: 22437-22444, 2005.
|
|
|
|
|
|
[PubMed: 15817459]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M501379200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Delgado-Olguin, P., Huang, Y., Li, X., Christodoulou, D., Seidman, C. E., Seidman, J. G., Tarakhovsky, A., Bruneau, B. G.
|
|
<strong>Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis.</strong>
|
|
Nature Genet. 44: 343-347, 2012.
|
|
|
|
|
|
[PubMed: 22267199]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.1068]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Di Meglio, T., Kratochwil, C. F., Vilain, N., Loche, A., Vitobello, A., Yonehara, K., Hrycaj, S. M., Roska, B., Peters, A. H. F. M., Eichmann, A., Wellik, D., Ducret, S., Rijli, F. M.
|
|
<strong>Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons.</strong>
|
|
Science 339: 204-207, 2013.
|
|
|
|
|
|
[PubMed: 23307742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1229326]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dohner, K., Brown, J., Hehmann, U., Hetzel, C., Stewart, J., Lowther, G., Scholl, C., Frohling, S., Cuneo, A., Tsui, L. C., Lichter, P., Scherer, S. W., Dohner, H.
|
|
<strong>Molecular cytogenetic characterization of a critical region in bands 7q35-q36 commonly deleted in malignant myeloid disorders.</strong>
|
|
Blood 92: 4031-4035, 1998.
|
|
|
|
|
|
[PubMed: 9834205]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ernst, T., Chase, A. J., Score, J., Hidalgo-Curtis, C. E., Bryant, C., Jones, A. V., Waghorn, K., Zoi, K., Ross, F. M., Reiter, A., Hochhaus, A., Drexler, H. G., Duncombe, A., Cervantes, F., Oscier, D., Boultwood, J., Grand, F. H., Cross, N. C.
|
|
<strong>Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.</strong>
|
|
Nature Genet. 42: 722-726, 2010.
|
|
|
|
|
|
[PubMed: 20601953]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.621]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ezhkova, E., Pasolli, H. A., Parker, J. S., Stokes, N., Su, I., Hannon, G., Tarakhovsky, A., Fuchs, E.
|
|
<strong>Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells.</strong>
|
|
Cell 136: 1122-1135, 2009.
|
|
|
|
|
|
[PubMed: 19303854]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2008.12.043]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fillmore, C. M., Xu, C., Desai, P. T., Berry, J. M., Rowbotham, S. P., Lin, Y.-J., Zhang, H., Marquez, V. E., Hammerman, P. S., Wong, K.-K., Kim, C. F.
|
|
<strong>EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors.</strong>
|
|
Nature 520: 239-242, 2015. Note: Erratum: Nature 563: E27, 2018.
|
|
|
|
|
|
[PubMed: 25629630]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature14122]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gibson, W. T., Hood, R. L., Zhan, S. H., Bulman, D. E., Fejes, A. P., Moore, R., Mungall, A. J., Eydoux, P., Babul-Hirji, R., An, J., Marra, M. A., FORGE Canada Consortium, Chitayat, D., Boycott, K. M., Weaver, D. D., Jones, S. J. M.
|
|
<strong>Mutations in EZH2 cause Weaver syndrome.</strong>
|
|
Am. J. Hum. Genet. 90: 110-118, 2012.
|
|
|
|
|
|
[PubMed: 22177091]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2011.11.018]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kamminga, L. M., Bystrykh, L. V., de Boer, A., Houwer, S., Douma, J., Weersing, E., Dontje, B., de Haan, G.
|
|
<strong>The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion.</strong>
|
|
Blood 107: 2170-2179, 2006.
|
|
|
|
|
|
[PubMed: 16293602]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2005-09-3585]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laible, G., Haynes, A. R., Lebersorger, A., O'Carroll, D., Mattei, M.-G., Denny, P., Brown, S. D. M., Jenuwein, T.
|
|
<strong>The murine polycomb-group genes Ezh1 and Ezh2 map close to Hox gene clusters on mouse chromosomes 11 and 6.</strong>
|
|
Mammalian Genome 10: 311-314, 1999.
|
|
|
|
|
|
[PubMed: 10051331]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s003359900993]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maier, V. K., Feeney, C. M., Taylor, J. E., Creech, A. L., Qiao, J. W., Szanto, A., Das, P. P., Chevrier, N., Cifuentes-Rojas, C., Orkin, S. H., Carr, S. A., Jaffe, J. D., Mertins, P., Lee, J. T.
|
|
<strong>Functional proteomic analysis of repressive histone methyltransferase complexes reveals ZNF518B as a G9A regulator.</strong>
|
|
Molec. Cell. Proteomics 14: 1435-1446, 2015.
|
|
|
|
|
|
[PubMed: 25680957]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/mcp.M114.044586]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Makishima, H., Jankowska, A. M., Tiu, R. V., Szpurka, H., Sugimoto, Y., Hu, Z., Saunthararajah, Y., Guinta, K., Keddache, M. A., Putnam, P., Sekeres, M. A., Moliterno, A. R., List, A. F., McDevitt, M. A., Maciejewski, J. P.
|
|
<strong>Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies.</strong>
|
|
Leukemia 24: 1799-1804, 2010.
|
|
|
|
|
|
[PubMed: 20724984]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/leu.2010.167]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Margueron, R., Justin, N., Ohno, K., Sharpe, M. L., Son, J., Drury, W. J., III, Voigt, P., Martin, S. R., Taylor, W. R., De Marco, V., Pirrotta, V., Reinberg, D., Gamblin, S. J.
|
|
<strong>Role of the polycomb protein EED in the propagation of repressive histone marks.</strong>
|
|
Nature 461: 762-767, 2009.
|
|
|
|
|
|
[PubMed: 19767730]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature08398]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McCabe, M. T., Ott, H. M., Ganji, G., Korenchuk, S., Thompson, C., Van Aller, G. S. Liu, Y., Graves, A. P., Pietra, A. D., III, Diaz, E., LaFrance, L. V., Mellinger, M., and 10 others.
|
|
<strong>EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.</strong>
|
|
Nature 492: 108-112, 2012.
|
|
|
|
|
|
[PubMed: 23051747]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11606]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Min, J., Zaslavsky, A., Fedele, G., McLaughlin, S. K., Reczek, E. E., De Raedt, T., Guney, I., Strochlic, D. E., MacConaill, L. E., Beroukhim, R., Bronson, R. T., Ryeom, S., Hahn, W. C., Loda, M., Cichowski, K.
|
|
<strong>An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappa-B.</strong>
|
|
Nature Med. 16: 286-294, 2010. Note: Erratum: Nature Med. 30: 1790 only, 2024.
|
|
|
|
|
|
[PubMed: 20154697]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm.2100]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morin, R. D., Johnson, N. A., Severson, T. M., Mungall, A. J., An, J., Goya, R., Paul, J. E., Boyle, M., Woolcock, B. W., Kuchenbauer, F., Yap, D., Humphries, R. K., and 26 others.
|
|
<strong>Somatic mutations altering EZH2 (tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.</strong>
|
|
Nature Genet. 42: 181-185, 2010.
|
|
|
|
|
|
[PubMed: 20081860]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.518]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nikoloski, G., Langemeijer, S. M. C., Kuiper, R. P., Knops, R., Massop, M., Tonnissen, E. R. L. T. M., van der Heijden, A., Scheele, T. N., Vandenberghe, P., de Witte, T., van der Reijden, B. A., Jansen, J. H.
|
|
<strong>Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes.</strong>
|
|
Nature Genet. 42: 665-667, 2010.
|
|
|
|
|
|
[PubMed: 20601954]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.620]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ntziachristos, P., Tsirigos, A., Van Vlierberghe, P., Nedjic, J., Trimarchi, T., Flaherty, M. S., Ferres-Marco, D., da Ros, V., Tang, Z., Siegle, J., Asp, P., Hadler, M., and 17 others.
|
|
<strong>Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia.</strong>
|
|
Nature Med. 18: 296-301, 2012.
|
|
|
|
|
|
[PubMed: 22237151]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm.2651]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
O'Carroll, D., Erhardt, S., Pagani, M., Barton, S. C., Surani, M. A., Jenuwein, T.
|
|
<strong>The polycomb-group gene Ezh2 is required for early mouse development.</strong>
|
|
Molec. Cell. Biol. 21: 4330-4336, 2001.
|
|
|
|
|
|
[PubMed: 11390661]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.21.13.4330-4336.2001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peng, D., Kryczek, I., Nagarsheth, N., Zhao, L., Wei, S., Wang, W., Sun, Y., Zhao, E., Vatan, L., Szeliga, W., Kotarski, J., Tarkowski, R., Dou, Y., Cho, K., Hensley-Alford, S., Munkarah, A., Liu, R., Zou, W.
|
|
<strong>Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy.</strong>
|
|
Nature 527: 249-253, 2015.
|
|
|
|
|
|
[PubMed: 26503055]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature15520]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Plath, K., Fang, J., Mlynarczyk-Evans, S. K., Cao, R., Worringer, K. A., Wang, H., de la Cruz, C. C., Otte, A. P., Panning, B., Zhang, Y.
|
|
<strong>Role of histone H3 lysine 27 methylation in X inactivation.</strong>
|
|
Science 300: 131-135, 2003.
|
|
|
|
|
|
[PubMed: 12649488]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1084274]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Su, I., Basavaraj, A., Krutchinsky, A. N., Hobert, O., Ullrich, A., Chait, B. T., Tarakhovsky, A.
|
|
<strong>Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement.</strong>
|
|
Nature Immun. 4: 124-131, 2003.
|
|
|
|
|
|
[PubMed: 12496962]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ni876]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tatton-Brown, K., Hanks, S., Ruark, E., Zachariou, A., Del Vecchio Duarte, S., Ramsay, E., Snape, K., Murray, A., Perdeaux, E. R., Seal, S., Loveday, C., Banka, S., and 16 others.
|
|
<strong>Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.</strong>
|
|
Oncotarget 2: 1127-33, 2011. Note: Erratum: Oncotarget 9: 36719, 2018.
|
|
|
|
|
|
[PubMed: 22190405]
|
|
|
|
|
|
[Full Text: https://doi.org/10.18632/oncotarget.385]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tatton-Brown, K., Rahman, N.
|
|
<strong>The NSD1 and EZH2 overgrowth genes, similarities and differences.</strong>
|
|
Am. J. Med. Genet. 163C: 86-91, 2013.
|
|
|
|
|
|
[PubMed: 23592277]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.c.31359]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Terranova,, R., Yokobayashi, S., Stadler, M. B., Otte, A. P., van Lohuizen, M., Orkin, S. H., Peters, A. H. F. M.
|
|
<strong>Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos.</strong>
|
|
Dev. Cell 15: 668-679, 2008.
|
|
|
|
|
|
[PubMed: 18848501]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.devcel.2008.08.015]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Varambally, S., Cao, Q., Mani, R.-S., Shankar, S., Wang, X., Ateeq, B., Laxman, B., Cao, X., Jing, X., Ramnarayanan, K., Brenner, J. C., Yu, J., Kim, J. H., Han, B., Tan, P., Kumar-Sinha, C., Lonigro, R. J., Palanisamy, N., Maher, C. A., Chinnaiyan, A. M.
|
|
<strong>Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer.</strong>
|
|
Science 322: 1695-1699, 2008.
|
|
|
|
|
|
[PubMed: 19008416]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1165395]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., Rubin, M. A., Chinnaiyan, A. M.
|
|
<strong>The polycomb group protein EZH2 is involved in progression of prostate cancer.</strong>
|
|
Nature 419: 624-629, 2002.
|
|
|
|
|
|
[PubMed: 12374981]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature01075]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vire, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.-M., Bollen, M., Esteller, M., Di Croce, L., de Launoit, Y., Fuks, F.
|
|
<strong>The polycomb group protein EZH2 directly controls DNA methylation.</strong>
|
|
Nature 439: 871-874, 2006. Note: Erratum: Nature 446: 824 only, 2007.
|
|
|
|
|
|
[PubMed: 16357870]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature04431]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weaver, D. D., Graham, C. B., Thomas, I. T., Smith, D. W.
|
|
<strong>A new overgrowth syndrome with accelerated skeletal maturation, unusual facies, and camptodactyly.</strong>
|
|
J. Pediat. 84: 547-552, 1974.
|
|
|
|
|
|
[PubMed: 4366187]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(74)80675-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Xu, C.-R., Cole, P. A., Meyers, D. J., Kormish, J., Dent, S., Zaret, K. S.
|
|
<strong>Chromatin 'prepattern' and histone modifiers in a fate choice for liver and pancreas.</strong>
|
|
Science 332: 963-966, 2011.
|
|
|
|
|
|
[PubMed: 21596989]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1202845]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Xu, K., Wu, Z. J., Groner, A. C., He, H. H., Cai. C., Lis, R. T., Wu, X., Stack, E. C., Loda, M., Liu, T., Xu, H., Cato, L., Thornton, J. E., Gregory, R. I., Morrissey, C., Vessella, R. L., Montironi, R., Magi-Galluzzi, C. Kantoff, P. W., Balk, S. P., Liu, X. S., Brown, M.
|
|
<strong>EZH2 oncogenic activity in castration-resistant prostate cancer cells is polycomb-independent.</strong>
|
|
Science 338: 1465-1469, 2012.
|
|
|
|
|
|
[PubMed: 23239736]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1227604]
|
|
|
|
|
|
</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">
|
|
Sonja A. Rasmussen - updated : 08/11/2022<br>Patricia A. Hartz - updated : 10/18/2017<br>Ada Hamosh - updated : 02/22/2016<br>Ada Hamosh - updated : 7/6/2015<br>Marla J. F. O'Neill - updated : 5/2/2013<br>Ada Hamosh - updated : 1/29/2013<br>Ada Hamosh - updated : 1/14/2013<br>Ada Hamosh - updated : 1/7/2013<br>Patricia A. Hartz - updated : 3/19/2012<br>Ada Hamosh - updated : 3/13/2012<br>Marla J. F. O'Neill - updated : 1/10/2012<br>Ada Hamosh - updated : 6/6/2011<br>Cassandra L. Kniffin - updated : 11/18/2010<br>Patricia A. Hartz - updated : 11/15/2010<br>Patricia A. Hartz - updated : 5/18/2010<br>Ada Hamosh - updated : 11/5/2009<br>Patricia A. Hartz - updated : 9/21/2009<br>Patricia A. Hartz - updated : 3/18/2009<br>Ada Hamosh - updated : 12/29/2008<br>Victor A. McKusick - updated : 2/23/2007<br>Ada Hamosh - updated : 12/6/2006<br>Ada Hamosh - updated : 10/25/2005<br>Ada Hamosh - updated : 4/15/2003<br>Paul J. Converse - updated : 1/23/2003<br>Ada Hamosh - updated : 11/13/2002<br>Ada Hamosh - updated : 10/18/2002<br>Victor A. McKusick - updated : 11/1/2000<br>Carol A. Bocchini - updated : 6/15/1999
|
|
</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 : 12/13/1996
|
|
</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 : 07/01/2024<br>alopez : 04/12/2024<br>carol : 08/12/2022<br>carol : 08/11/2022<br>carol : 12/16/2019<br>carol : 10/10/2019<br>alopez : 03/28/2019<br>carol : 11/14/2017<br>ckniffin : 11/10/2017<br>mgross : 10/18/2017<br>alopez : 02/22/2016<br>alopez : 7/6/2015<br>alopez : 7/6/2015<br>carol : 5/2/2013<br>mgross : 2/5/2013<br>alopez : 1/31/2013<br>terry : 1/29/2013<br>alopez : 1/15/2013<br>terry : 1/14/2013<br>alopez : 1/7/2013<br>terry : 1/7/2013<br>mgross : 3/19/2012<br>terry : 3/19/2012<br>alopez : 3/15/2012<br>terry : 3/13/2012<br>terry : 1/20/2012<br>carol : 1/10/2012<br>alopez : 6/13/2011<br>terry : 6/6/2011<br>wwang : 11/23/2010<br>ckniffin : 11/18/2010<br>mgross : 11/16/2010<br>terry : 11/15/2010<br>mgross : 5/19/2010<br>mgross : 5/18/2010<br>terry : 5/18/2010<br>alopez : 11/9/2009<br>alopez : 11/9/2009<br>terry : 11/5/2009<br>mgross : 10/2/2009<br>terry : 9/21/2009<br>mgross : 3/18/2009<br>terry : 3/18/2009<br>alopez : 12/30/2008<br>alopez : 12/29/2008<br>terry : 12/29/2008<br>terry : 5/9/2007<br>alopez : 4/27/2007<br>alopez : 3/2/2007<br>terry : 2/23/2007<br>alopez : 12/20/2006<br>alopez : 12/20/2006<br>terry : 12/6/2006<br>alopez : 10/26/2005<br>alopez : 10/26/2005<br>terry : 10/25/2005<br>terry : 5/15/2003<br>alopez : 4/17/2003<br>terry : 4/15/2003<br>alopez : 1/31/2003<br>mgross : 1/23/2003<br>alopez : 11/14/2002<br>terry : 11/13/2002<br>alopez : 10/21/2002<br>alopez : 10/21/2002<br>terry : 10/18/2002<br>mgross : 6/4/2001<br>terry : 1/18/2001<br>mcapotos : 11/9/2000<br>mcapotos : 11/9/2000<br>mcapotos : 11/8/2000<br>mcapotos : 11/7/2000<br>terry : 11/1/2000<br>carol : 6/15/1999<br>alopez : 8/6/1998<br>alopez : 6/23/1998<br>terry : 2/4/1997<br>mark : 12/16/1996
|
|
</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>
|
|
|
|
|