3718 lines
293 KiB
Text
3718 lines
293 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
|
|
|
|
- *612778 - SET DOMAIN-CONTAINING PROTEIN 2; SETD2
|
|
|
|
|
|
- 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=612778"><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">*612778</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="#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">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/612778">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=ENSG00000181555;t=ENST00000409792" 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=29072" 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=612778" 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=ENSG00000181555;t=ENST00000409792" 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_001349370,NM_014159,NR_146158,XM_024453487,XM_024453488,XM_024453489,XM_047448045,XR_002959514,XR_007095670,XR_007095671,XR_007095672,XR_007095673" 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_014159" 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=612778" 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=11043&isoform_id=11043_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/SETD2" 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/3319282,3329423,6841376,10438874,12697196,19584401,20521978,34534845,47077203,47938153,50512435,50512437,50949432,50949534,60688116,109658484,109658962,119585209,119585210,119585211,119585212,119585213,119585214,119585215,197313748,296452963,1159261138,1370483941,1370483943,1370483955,2217343626" 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/Q9BYW2" 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=29072" 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=ENSG00000181555;t=ENST00000409792" 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=SETD2" 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=SETD2" 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+29072" 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/SETD2" 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:29072" 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/29072" 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=chr3&hgg_gene=ENST00000409792.4&hgg_start=47016436&hgg_end=47164840&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/gene-dosage/HGNC:18420" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:18420" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=612778[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=612778[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/SETD2/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/ENSG00000181555" 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=SETD2" 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=SETD2" 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=SETD2" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SETD2&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/PA143485612" 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:18420" 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/FBgn0030486.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:1918177" 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/SETD2#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:1918177" 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/29072/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=29072" 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=WBGene00016603;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-030131-2140" 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:29072" 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=SETD2&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> 1300117002<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>
|
|
612778
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SET DOMAIN-CONTAINING PROTEIN 2; SETD2
|
|
|
|
</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">
|
|
SET2<br />
|
|
HUNTINGTIN-INTERACTING PROTEIN B; HYPB<br />
|
|
HUNTINGTIN-BINDING PROTEIN, 231-KD; HBP231<br />
|
|
KIAA1732
|
|
</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=SETD2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SETD2</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/3/262?start=-3&limit=10&highlight=262">3p21.31</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:47016436-47164840&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'})">3:47,016,436-47,164,840</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=620157,616831,620155" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/3/262?start=-3&limit=10&highlight=262">
|
|
3p21.31
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Intellectual developmental disorder, autosomal dominant 70
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620157"> 620157 </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>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Luscan-Lumish syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616831"> 616831 </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>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Rabin-Pappas syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620155"> 620155 </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/612778" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/612778" 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>Methylation of histone H3 (see <a href="/entry/602810">602810</a>) lys36 (H3K36) is associated with transcribed regions and functions in transcription fidelity, RNA splicing, and DNA repair. SETD2 is the primary methyltransferase catalyzing H3K36 trimethylation (H3K36me3) (summary by <a href="#18" class="mim-tip-reference" title="Xu, Q., Xiang, Y., Wang, Q., Wang, L., Brind'Amour, J., Bogutz, A. B., Zhang, Y., Yu, G., Xia, W., Du, Z., Huang, C., and 12 others. <strong>SETD2 regulates the maternal epigenome, genomic imprinting and embryonic development.</strong> Nature Genet. 51: 844-856, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31040401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31040401</a>] [<a href="https://doi.org/10.1038/s41588-019-0398-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31040401">Xu et al., 2019</a>) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31040401" 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>Huntington disease (<a href="/entry/143100">143100</a>) is caused by expansion of a CAG trinucleotide repeat encoding an N-terminal polyglutamine region in huntingtin (HTT; <a href="/entry/613004">613004</a>) to more than 34 units. Using N-terminal domains of HTT containing 58 or 62 glutamines in a yeast 2-hybrid assay of a fetal brain cDNA library, followed by database analysis and screening brain and testis cDNA libraries, <a href="#3" class="mim-tip-reference" title="Faber, P. W., Barnes, G. T., Srinidhi, J., Chen, J., Gusella, J. F., MacDonald, M. E. <strong>Huntingtin interacts with a family of WW domain proteins.</strong> Hum. Molec. Genet. 7: 1463-1474, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9700202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9700202</a>] [<a href="https://doi.org/10.1093/hmg/7.9.1463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9700202">Faber et al. (1998)</a> obtained a partial SETD2 clone, which they called HYPB. The deduced protein has a WW domain. Northern blot analysis detected a transcript of about 9.0 kb that was variably expressed in all tissues examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9700202" 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 sequencing clones obtained from a size-fractionated adult brain cDNA library, <a href="#10" class="mim-tip-reference" title="Nagase, T., Kikuno, R., Hattori, A., Kondo, Y., Okumura, K., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes, XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 7: 347-355, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11214970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11214970</a>] [<a href="https://doi.org/10.1093/dnares/7.6.347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11214970">Nagase et al. (2000)</a> cloned SETD2, which they designated KIAA1732. The deduced protein contains 1,325 amino acids. RT-PCR detected low SETD2 expression in all adult and fetal tissues and specific adult brain regions examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11214970" 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 a yeast 1-hybrid screen of a HeLa cell cDNA library to identify proteins that could bind transcriptional start site-2 (TS2) of the adenovirus E1A gene, followed by RT-PCR of normal human foreskin fibroblasts, <a href="#15" class="mim-tip-reference" title="Rega, S., Stiewe, T., Chang, D.-I., Pollmeier, B., Esche, H., Bardenheuer, W., Marquitan, G., Putzer, B. M. <strong>Identification of full-length huntingtin-interacting protein p231HBP/HYPB as a DNA-binding factor.</strong> Molec. Cell. Neurosci. 18: 68-79, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11461154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11461154</a>] [<a href="https://doi.org/10.1006/mcne.2001.1004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11461154">Rega et al. (2001)</a> cloned full-length SETD2, which they called HBP231. The deduced 2,061-amino acid protein has a calculated molecular mass of about 231 kD. It has a putative N-terminal tyrosine phosphorylation site, a central SET domain, and a C-terminal WW/WWP domain that is followed by a putative nuclear localization signal. The C-terminal region of HBP231 corresponds to the HYPB sequence. Northern blot analysis detected a 7.5-kb transcript expressed at variable levels in all tissues examined. Western blot analysis of HeLa cells showed that HBP231 had an apparent molecular mass of 231 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11461154" 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>By FISH and genomic sequence analysis, <a href="#15" class="mim-tip-reference" title="Rega, S., Stiewe, T., Chang, D.-I., Pollmeier, B., Esche, H., Bardenheuer, W., Marquitan, G., Putzer, B. M. <strong>Identification of full-length huntingtin-interacting protein p231HBP/HYPB as a DNA-binding factor.</strong> Molec. Cell. Neurosci. 18: 68-79, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11461154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11461154</a>] [<a href="https://doi.org/10.1006/mcne.2001.1004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11461154">Rega et al. (2001)</a> mapped the SETD2 gene to chromosome 3p21.3-p21.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11461154" 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>Using a yeast 2-hybrid assay, <a href="#3" class="mim-tip-reference" title="Faber, P. W., Barnes, G. T., Srinidhi, J., Chen, J., Gusella, J. F., MacDonald, M. E. <strong>Huntingtin interacts with a family of WW domain proteins.</strong> Hum. Molec. Genet. 7: 1463-1474, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9700202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9700202</a>] [<a href="https://doi.org/10.1093/hmg/7.9.1463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9700202">Faber et al. (1998)</a> showed that HYPB interacted with normal and mutant huntingtin in extracts of Huntington disease lymphoblastoid cells. The interaction was mediated by the WW domain region of HYPB and by the N-terminal proline-rich region in huntingtin, and it was enhanced by lengthening the adjacent glutamine tract. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9700202" 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 electrophoretic mobility shift analysis with nuclear extracts of HeLa cells, <a href="#15" class="mim-tip-reference" title="Rega, S., Stiewe, T., Chang, D.-I., Pollmeier, B., Esche, H., Bardenheuer, W., Marquitan, G., Putzer, B. M. <strong>Identification of full-length huntingtin-interacting protein p231HBP/HYPB as a DNA-binding factor.</strong> Molec. Cell. Neurosci. 18: 68-79, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11461154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11461154</a>] [<a href="https://doi.org/10.1006/mcne.2001.1004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11461154">Rega et al. (2001)</a> confirmed that endogenous HBP231 bound the TS2 motif of the adenovirus E1A promoter in a sequence-specific manner. HBP231 expression was elevated in human embryonic kidney cells expressing E1A, suggesting that the observed autoactivation of E1A may be achieved by induced HBP231 expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11461154" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Sun, X.-J., Wei, J., Wu, X.-Y., Hu, M., Wang, L., Wang, H.-H., Zhang, Q.-H., Chen, S.-J., Huang, Q.-H., Chen, Z. <strong>Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase.</strong> J. Biol. Chem. 280: 35261-35271, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16118227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16118227</a>] [<a href="https://doi.org/10.1074/jbc.M504012200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16118227">Sun et al. (2005)</a> showed that the SET domain and flanking AWS and postSET domains of human HBP231 mediated H3K36-specific histone methyltransferase activity. The isolated low-charged region of HBP231 immediately following the WW domain showed transcriptional activity, although a longer construct did not. A C-terminal fragment of HBP231 containing the AWS, SET, and postSET domains, the low-charged region, and the WW domain associated with hyperphosphorylated RNA polymerase II (see <a href="/entry/180660">180660</a>), but not with the unphosphorylated form. Domain analysis revealed that the region C-terminal to the WW domain mediated the interaction of HBP231 with phosphorylated RNA polymerase II. <a href="#16" class="mim-tip-reference" title="Sun, X.-J., Wei, J., Wu, X.-Y., Hu, M., Wang, L., Wang, H.-H., Zhang, Q.-H., Chen, S.-J., Huang, Q.-H., Chen, Z. <strong>Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase.</strong> J. Biol. Chem. 280: 35261-35271, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16118227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16118227</a>] [<a href="https://doi.org/10.1074/jbc.M504012200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16118227">Sun et al. (2005)</a> concluded that HBP231 may coordinate histone methylation and transcriptional regulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16118227" 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 yeast histone deacetylase Rpd3 is recruited to promoters and represses transcription initiation. <a href="#1" class="mim-tip-reference" title="Carrozza, M. J., Li, B., Florens, L., Suganuma, T., Swanson, S. K., Lee, K. K., Shia, W.-J., Anderson, S., Yates, J., Washburn, M. P., Workman, J. L. <strong>Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription.</strong> Cell 123: 581-592, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16286007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16286007</a>] [<a href="https://doi.org/10.1016/j.cell.2005.10.023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16286007">Carrozza et al. (2005)</a> and <a href="#6" class="mim-tip-reference" title="Keogh, M.-C., Kurdistani, S. K., Morris, S. A., Ahn, S. H., Podolny, V., Collins, S. R., Schuldiner, M., Chin, K., Punna, T., Thompson, N. J., Boone, C., Emili, A., Weissman, J. S., Hughes, T. R., Strahl, B. D., Grunstein, M., Greenblatt, J. F., Buratowski, S., Krogan, N. J. <strong>Cotranscriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.</strong> Cell 123: 593-605, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16286008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16286008</a>] [<a href="https://doi.org/10.1016/j.cell.2005.10.025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16286008">Keogh et al. (2005)</a> independently showed that the yeast SETD2 ortholog, Set2, is a histone H3K36 methyltransferase associated with a small Rpd3 complex that signals deacetylation of ORFs by Rpd3 and suppresses transcription initiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16286007+16286008" 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 immunoprecipitation and pull-down analyses, <a href="#13" class="mim-tip-reference" title="Park, I. Y., Powell, R. T., Tripathi, D. N., Dere, R., Ho, T. H., Blasius, T. L., Chiang, Y. C., Davis, I. J., Fahey, C. C., Hacker, K. E., Verhey, K. J., Bedford, M. T., Jonasch, E., Rathmell, W. K., Walker, C. L. <strong>Dual chromatin and cytoskeletal remodeling by SETD2.</strong> Cell 166: 950-962, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27518565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27518565</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27518565[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.2016.07.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27518565">Park et al. (2016)</a> showed that human SETD2 bound directly to alpha-tubulin (see <a href="/entry/602529">602529</a>) in vitro through its SET domain to methylate alpha-tubulin at K40. Analysis in mouse embryonic fibroblasts (MEFs) indicated that microtubule methylation occurred during mitosis and cytokinesis, which could be completed through the catalytic activity of Setd2. Mass spectrometric analysis revealed that methylation of alpha-tubulin at K40 by SETD2 also occurred in vivo and identified SETD2 as a dual-function methyltransferase that directly methylated both histones and alpha-tubulin. Moreover, analysis of MEFs from Setd2 -/- mice showed that Setd2 was a mitotic microtubule methyltransferase, as methylation of microtubules was lost in Setd2 -/- MEFs. Setd2 was required for genomic stability and normal mitosis and cytokinesis, as Setd2 -/- MEFs displayed increase in ploidy and polynucleation, as well as elevated defects in mitosis and cytokinesis. Further analysis with human cells showed that loss of alpha-tubulin methylation by SETD2 caused mitotic and cytokinesis defects, confirming SETD2 as a dual-function methyltransferase for both chromatin and the cytoskeleton. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27518565" 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 bioinformatic analysis, <a href="#4" class="mim-tip-reference" title="Hacker, K. E., Fahey, C. C., Shinsky, S. A., Chiang, Y. J., DiFiore, J. V., Jha, D. K., Vo, A. H., Shavit, J. A., Davis, I. J., Strahl, B. D., Rathmell, W. K. <strong>Structure/function analysis of recurrent mutations in SETD2 protein reveals a critical and conserved role for a SET domain residue in maintaining protein stability and histone H3 lys-36 trimethylation.</strong> J. Biol. Chem. 291: 21283-21295, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27528607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27528607</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27528607[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M116.739375" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27528607">Hacker et al. (2016)</a> identified a high degree of structural and sequence homology between human SETD2 and its yeast ortholog, Set2, especially in their SET and SRI domains. Expression of SETD2 with SET domain mutations, which is found in some cancer cells, especially clear-cell renal cell carcinoma, in SETD2-deficient human cells revealed that different mutations differentially destabilized SETD2 and had separate effects on histone H3K36me3. One SET domain mutation, arg1625 to cys (R1625C), resulted in decreased RNA and a shortened protein half-life, and analysis with purified recombinant protein showed that loss of catalytic activity for this mutant was not due to protein misfolding or reduced thermal stability but rather to diminished substrate binding. Likewise, domain-specific mutations in Set2 resulted in different effects on H3K36 methylation status in yeast. However, in contrast with human cells, histone H3K36me2 was indispensable, whereas H3K36me3 was dispensable. Further analysis demonstrated that SETD2-mediated H3K36me3 in human cells was coupled to efficient resolution of double-strand breaks and the DNA damage response. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27528607" 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 chromatin immunoprecipitation-sequencing analysis, <a href="#18" class="mim-tip-reference" title="Xu, Q., Xiang, Y., Wang, Q., Wang, L., Brind'Amour, J., Bogutz, A. B., Zhang, Y., Yu, G., Xia, W., Du, Z., Huang, C., and 12 others. <strong>SETD2 regulates the maternal epigenome, genomic imprinting and embryonic development.</strong> Nature Genet. 51: 844-856, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31040401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31040401</a>] [<a href="https://doi.org/10.1038/s41588-019-0398-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31040401">Xu et al. (2019)</a> showed that H3K36me3 correlated with DNA methylation in fully grown mouse oocytes. However, H3K36me3 was mutually exclusive with H3K4me3 and H3K27me3, and global H3K36me3 and H3K27me3 were unaffected in the absence of DNA methylation. Depletion of Setd2 in mouse oocytes resulted in reduced metaphase II oocyte number and sterility of female mice. H3K36me3 was lost in Setd2-deficient oocytes and led to alteration of the global DNA methylation level, redistribution of H3K4me3 and H3K27me3, and a subsequent change in chromatin accessibility. The redistribution of H3K27me3, but not H3K4me3, partially resulted in aberrant gene expression in Setd2-deficient oocytes. Setd2 promoted the establishment of maternal imprints, likely through H3K36me3-mediated recruitment of Dnmt3a (<a href="/entry/602769">602769</a>)/Dnmt3l (<a href="/entry/606588">606588</a>) and simultaneous inhibition of H3K4me3. As a result, maternal imprints and ectopic H3K4me3 at imprinting control regions were lost in Setd2-deficient oocytes. The authors found that maternal H3K36me3 was transiently inherited in early embryos after fertilization, just like H3K4me3 and H3K27me3 during early development. The defective maternal epigenome and aberrant gene expression observed in Setd2-deficient oocytes were inherited in 1-cell embryos after fertilization. Consequently, maternal depletion of Setd2 resulted in absence of maternal DNA replication and failure of zygotic genome activation and maternal RNA clearance, leading to 1-cell arrest after implantation and causing lethality of Setd2-deficient embryos. Further investigation demonstrated that both oocyte cytoplasm and chromatin defects contributed to lethality of Setd2-deficient embryos, and that Setd2-dependent patterning of the maternal epigenome was essential for postimplantation development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31040401" 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>Luscan-Lumish syndrome</em></strong></p><p>
|
|
O'Roak et al. (<a href="#11" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">2012</a>, <a href="#12" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., Turner, E. H., Stanaway, I. B., and 11 others. <strong>Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.</strong> Nature 485: 246-250, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22495309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22495309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22495309[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/nature10989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22495309">2012</a>) sequenced a total of 677 individual exomes from 209 families from the autism spectrum disorder (ASD) Simons Simplex Collection (SSC) and identified 4 individuals with ASD and heterozygous mutations in the SETD2 gene: 2 with nonsense mutations (paternally-inherited C94X and maternally-inherited Q7X), 1 with a de novo I42F missense mutation, and 1 (patient 12565.p1) with a de novo frameshift mutation. <a href="#7" class="mim-tip-reference" title="Lumish, H. S., Wynn, J., Devinsky, O., Chung, W. K. <strong>SETD2 mutation in a child with autism, intellectual disabilities and epilepsy.</strong> J. Autism Dev. Disord. 45: 3764-3770, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26084711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26084711</a>] [<a href="https://doi.org/10.1007/s10803-015-2484-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26084711">Lumish et al. (2015)</a> stated that the patient with the frameshift mutation (<a href="#0001">612778.0001</a>) also had a history of failure to thrive, nonfebrile seizures starting at 4 years of age, motor delays, low-normal nonverbal IQ, and macrocephaly, termed Luscan-Lumish syndrome (LLS; <a href="/entry/616831">616831</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23160955+26084711+22495309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Iossifov, I., O'Roak, B. J., Sanders, S. J., Ronemus, M., Krumm, N., Levy, D., Stessman, H. A., Vives, L., Patterson, K. E., Smith, J. D., Paeper, B., and 35 others. <strong>The contribution of de novo coding mutations to autism spectrum disorder.</strong> Nature 515: 216-221, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25363768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25363768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25363768[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/nature13908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25363768">Iossifov et al. (2014)</a> sequenced exomes from more than 2,500 simplex families, each having a child with ASD, and identified 2 unrelated individuals with mutations in the SETD2 gene, a 1-basepair deletion and a missense variant. Most of the families were from the ASD SSC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25363768" 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 2 'Sotos syndrome-like' patients, <a href="#8" class="mim-tip-reference" title="Luscan, A., Laurendeau, I., Malan, V., Francannet, C., Odent, S., Giuliano, F., Lacombe, D., Touraine, R., Vidaud, M., Pasmant, E., Cormier-Daire, V. <strong>Mutations in SETD2 cause a novel overgrowth condition.</strong> J. Med. Genet. 51: 512-517, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24852293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24852293</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24852293">Luscan et al. (2014)</a> identified heterozygous mutations in the SETD2 gene (<a href="#0002">612778.0002</a> and <a href="#0003">612778.0003</a>). Neither variant was reported in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24852293" 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 whole-exome sequencing in a 17-year-old girl with Luscan-Lumish syndrome, <a href="#7" class="mim-tip-reference" title="Lumish, H. S., Wynn, J., Devinsky, O., Chung, W. K. <strong>SETD2 mutation in a child with autism, intellectual disabilities and epilepsy.</strong> J. Autism Dev. Disord. 45: 3764-3770, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26084711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26084711</a>] [<a href="https://doi.org/10.1007/s10803-015-2484-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26084711">Lumish et al. (2015)</a> identified a heterozygous de novo frameshift mutation (<a href="#0004">612778.0004</a>) in the SETD2 gene. The mutation was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project database, in the dbSNP database, or in over 9,000 clinical exomes sequenced at GeneDx. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26084711" 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 2 patients with intellectual disability, speech delay, autism spectrum disorder, and macrocephaly consistent with Luscan-Lumish syndrome, <a href="#17" class="mim-tip-reference" title="van Rij, M. C., Hollink, I. H. I. M., Terhal, P. A., Kant, S. G., Ruivenkamp, C., van Haeringen, A., Kievit, J. A., van Belzen, M. J. <strong>Two novel cases expanding the phenotype of SETD2-related overgrowth syndrome.</strong> Am. J. Med. Genet. 176A: 1212-1215, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29681085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29681085</a>] [<a href="https://doi.org/10.1002/ajmg.a.38666" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29681085">van Rij et al. (2018)</a> identified de novo heterozygous frameshift mutations in the SETD2 gene (NM_014159.6). These included a deletion/insertion (c.1647_1667delinsAC) in exon 3 and a single base-pair deletion (c.6775delG) in exon 15, both resulting in a frameshift and a premature stop codon. The variants were not present in the unaffected parents of either patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29681085" 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 Luscan-Lumish syndrome, <a href="#9" class="mim-tip-reference" title="Marzin, P., Rondeau, S., Aldinger, K. A., Alessandri, J. L., Isidor, B., Heron, D., Keren, B., Dobyns, W. B., Cormier-Daire, V. <strong>SETD2 related overgrowth syndrome: Presentation of four new patients and review of the literature.</strong> Am. J. Med. Genet. 181C: 509-518, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31643139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31643139</a>] [<a href="https://doi.org/10.1002/ajmg.c.31746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31643139">Marzin et al. (2019)</a> identified 2 nonsense mutations (K1426X and Y2157X) and 2 missense mutations (Y1666C and R1625H) in the SETD2 gene (NM_014159.6), all of which were located in the catalytic domain SET2. In a review of their 4 patients and 9 previously reported patients with LLS, the authors found that the mutations were intragenic loss-of-function variants (69% truncating and 31% missense) distributed throughout the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31643139" 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 targeting sequencing in 2 patients with autism spectrum disorder and other features of Luscan-Lumish syndrome, <a href="#2" class="mim-tip-reference" title="Chen, M., Quan, Y., Duan, G., Wu, H., Bai, T., Wang, Y., Zhou, S., Ou, J., Shen, Y., Hu, Z., Xia, K., Guo, H. <strong>Mutation pattern and genotype-phenotype correlations of SETD2 in neurodevelopmental disorders.</strong> Europ. J. Med. Genet. 64: 104200, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33766796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33766796</a>] [<a href="https://doi.org/10.1016/j.ejmg.2021.104200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33766796">Chen et al. (2021)</a> identified 2 de novo mutations in the SETD2 gene (NM_014159): a splicing mutation (c.4715+1G-A) and a missense mutation (c.3185C-T, P1062L). Neither variant was reported in large public databases. The authors also evaluated 17 reported de novo SETD2 variants (8 frameshift, 1 nonsense, 7 missense, 1 in-frame deletion). All missense variants occurred at residues that were evolutionarily conserved. Using ACMG criteria, 13 of the 19 variants were classified as pathogenic, 5 as likely pathogenic, and one (missense) as a variant of uncertain significance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33766796" 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>Rabin-Pappas Syndrome</em></strong></p><p>
|
|
In 12 unrelated patients (group 1) with Rabin-Pappas syndrome (RAPAS; <a href="/entry/620155">620155</a>), <a href="#14" class="mim-tip-reference" title="Rabin, R., Radmanesh, A., Glass, I. A., Dobyns, W. B., Aldinger, K. A., Shieh, J. T., Romoser, S., Bombei, H., Dowsett, L., Trapane, P., Bernat, J. A., Baker, J., and 29 others. <strong>Genotype-phenotype correlation at codon 1740 of SETD2.</strong> Am. J. Med. Genet. 182A: 2037-2048, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32710489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32710489</a>] [<a href="https://doi.org/10.1002/ajmg.a.61724" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32710489">Rabin et al. (2020)</a> identified a de novo heterozygous missense mutation in the SETD2 gene (R1740W; <a href="#0005">612778.0005</a>). The mutation, which was found through clinical genetics services, was not present in the gnomAD database. The patients were ascertained through collaborative efforts, and the phenotype determined retrospectively. Functional studies of the variant and studies of patient cells were not performed. The patients had a severe phenotype with intellectual disability, inability to walk or speak, and involvement of multiple organ systems, which was considered to be different from that of patients with other mutations in SETD2 gene, including those with a different mutation at the same codon (R1740Q; <a href="#0006">612778.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32710489" 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>Intellectual Developmental Disorder 70, Autosomal Dominant</em></strong></p><p>
|
|
In 3 unrelated patients (group 2) with autosomal dominant intellectual developmental disorder-70 (MRD70; <a href="/entry/620157">620157</a>), <a href="#14" class="mim-tip-reference" title="Rabin, R., Radmanesh, A., Glass, I. A., Dobyns, W. B., Aldinger, K. A., Shieh, J. T., Romoser, S., Bombei, H., Dowsett, L., Trapane, P., Bernat, J. A., Baker, J., and 29 others. <strong>Genotype-phenotype correlation at codon 1740 of SETD2.</strong> Am. J. Med. Genet. 182A: 2037-2048, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32710489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32710489</a>] [<a href="https://doi.org/10.1002/ajmg.a.61724" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32710489">Rabin et al. (2020)</a> identified a de novo heterozygous missense mutation in the SETD2 gene (R1740Q; <a href="#0006">612778.0006</a>). The mutation, which was found through clinical genetics services, was not present in the gnomAD database. The patients were ascertained through collaborative efforts, and the phenotype determined retrospectively. Functional studies of the variant and studies of patient cells were not performed. The patients had developmental delay with moderately impaired intellectual development, low-normal head circumference, variable and mild dysmorphic features, and absence of additional congenital anomalies or systemic involvement. The phenotype was considered to be different from that of patients with other mutations in the SETD2 gene, including those with a different mutation at the same codon (R1740W; <a href="#0005">612778.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32710489" 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/612778" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=612778[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 LUSCAN-LUMISH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SETD2, 1-BP DEL, 6341A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs869025569 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869025569;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=rs869025569" 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=rs869025569" 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=RCV000208546" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000208546" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000208546</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By exome sequencing of patients from the Simons Simplex Collection, <a href="#11" class="mim-tip-reference" title="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> identified a de novo heterozygous 1-bp deletion (c.6341delA, NM_014159) in the SETD2 gene, resulting in a frameshift (Asn2114IlefsTer33) in a female (patient 12565.p1) with autism spectrum disorder. <a href="#7" class="mim-tip-reference" title="Lumish, H. S., Wynn, J., Devinsky, O., Chung, W. K. <strong>SETD2 mutation in a child with autism, intellectual disabilities and epilepsy.</strong> J. Autism Dev. Disord. 45: 3764-3770, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26084711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26084711</a>] [<a href="https://doi.org/10.1007/s10803-015-2484-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26084711">Lumish et al. (2015)</a> stated that this patient also had failure to thrive, seizures, motor delay, low-normal IQ, and macrocephaly (Luscan-Lumish syndrome, <a href="/entry/616831">616831</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23160955+26084711" 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 LUSCAN-LUMISH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SETD2, LEU1815TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs869025570 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869025570;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=rs869025570" 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=rs869025570" 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=RCV000208561" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000208561" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000208561</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 26-year-old French man with Luscan-Lumish syndrome (LLS; <a href="/entry/616831">616831</a>), who was diagnosed with a 'Sotos-like syndrome,' <a href="#8" class="mim-tip-reference" title="Luscan, A., Laurendeau, I., Malan, V., Francannet, C., Odent, S., Giuliano, F., Lacombe, D., Touraine, R., Vidaud, M., Pasmant, E., Cormier-Daire, V. <strong>Mutations in SETD2 cause a novel overgrowth condition.</strong> J. Med. Genet. 51: 512-517, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24852293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24852293</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24852293">Luscan et al. (2014)</a> identified a de novo heterozygous c.5444T-G transversion (c.5444T-G, NM_014159.6) in the SETD2 gene, resulting in a leu1815-to-trp (L1815W) substitution at a conserved residue. The mutation was not found in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24852293" 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 LUSCAN-LUMISH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SETD2, GLN274TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs869025571 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869025571;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=rs869025571" 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=rs869025571" 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=RCV000208536" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000208536" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000208536</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 23-year-old woman with Luscan-Lumish syndrome (LLS; <a href="/entry/616831">616831</a>), who was diagnosed with 'Sotos-like syndrome,' <a href="#8" class="mim-tip-reference" title="Luscan, A., Laurendeau, I., Malan, V., Francannet, C., Odent, S., Giuliano, F., Lacombe, D., Touraine, R., Vidaud, M., Pasmant, E., Cormier-Daire, V. <strong>Mutations in SETD2 cause a novel overgrowth condition.</strong> J. Med. Genet. 51: 512-517, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24852293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24852293</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24852293">Luscan et al. (2014)</a> identified a heterozygous c.820C-T transition (c.820C-T, NM_014159.6), resulting in a gln274-to-ter (Q274X) substitution. The woman was adopted and her biologic parents could not be tested. The mutation was not found in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24852293" 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 LUSCAN-LUMISH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SETD2, 1-BP DEL, 2028T
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs869025572 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869025572;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=rs869025572" 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=rs869025572" 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=RCV000208551" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000208551" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000208551</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By whole-exome sequencing in a 17-year-old girl with Luscan-Lumish syndrome (LLS; <a href="/entry/616831">616831</a>), <a href="#7" class="mim-tip-reference" title="Lumish, H. S., Wynn, J., Devinsky, O., Chung, W. K. <strong>SETD2 mutation in a child with autism, intellectual disabilities and epilepsy.</strong> J. Autism Dev. Disord. 45: 3764-3770, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26084711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26084711</a>] [<a href="https://doi.org/10.1007/s10803-015-2484-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26084711">Lumish et al. (2015)</a> identified a heterozygous de novo 1-bp deletion (c.2028delT, NM_014159.6) in the SETD2 gene, resulting in a frameshift (Pro677LeufsTer19). This mutations was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project database, in the dbSNP database, or in over 9,000 clinical exomes sequenced at GeneDx. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26084711" 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 RABIN-PAPPAS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SETD2, ARG1740TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1057523157 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057523157;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=rs1057523157" 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=rs1057523157" 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=RCV000426759 OR RCV000779643 OR RCV000853394 OR RCV001258009 OR RCV001267453 OR RCV001267684 OR RCV002467447 OR RCV004554776" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000426759, RCV000779643, RCV000853394, RCV001258009, RCV001267453, RCV001267684, RCV002467447, RCV004554776" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000426759...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 12 unrelated patients (group 1) with Rabin-Pappas syndrome (RAPAS; <a href="/entry/620155">620155</a>), <a href="#14" class="mim-tip-reference" title="Rabin, R., Radmanesh, A., Glass, I. A., Dobyns, W. B., Aldinger, K. A., Shieh, J. T., Romoser, S., Bombei, H., Dowsett, L., Trapane, P., Bernat, J. A., Baker, J., and 29 others. <strong>Genotype-phenotype correlation at codon 1740 of SETD2.</strong> Am. J. Med. Genet. 182A: 2037-2048, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32710489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32710489</a>] [<a href="https://doi.org/10.1002/ajmg.a.61724" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32710489">Rabin et al. (2020)</a> identified a de novo heterozygous c.5218C-T transition (c.5218C-T, NM_014159.6) in the SETD2 gene, resulting in an arg1740-to-trp (R1740W) substitution at conserved residue in a region of unknown function. The mutation, which was found through clinical genetics services, was not present in the gnomAD database. The patients were ascertained through collaborative efforts, and the phenotype determined retrospectively. Functional studies of the variant and studies of patient cells were not performed. The patients had a severe phenotype with intellectual disability, inability to walk or speak, and involvement of multiple organ systems, which was considered to be different from that of patients with other SETD2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32710489" 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 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 70</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SETD2, ARG1740GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2107651195 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2107651195;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=rs2107651195" 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=rs2107651195" 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=RCV001823014 OR RCV002259402 OR RCV002467456" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001823014, RCV002259402, RCV002467456" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001823014...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 unrelated patients (group 2) with autosomal dominant intellectual developmental disorder-70 (MRD70; <a href="/entry/620157">620157</a>), <a href="#14" class="mim-tip-reference" title="Rabin, R., Radmanesh, A., Glass, I. A., Dobyns, W. B., Aldinger, K. A., Shieh, J. T., Romoser, S., Bombei, H., Dowsett, L., Trapane, P., Bernat, J. A., Baker, J., and 29 others. <strong>Genotype-phenotype correlation at codon 1740 of SETD2.</strong> Am. J. Med. Genet. 182A: 2037-2048, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32710489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32710489</a>] [<a href="https://doi.org/10.1002/ajmg.a.61724" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32710489">Rabin et al. (2020)</a> identified a de novo heterozygous c.5219G-A transition (c.5219G-A, NM_014159.6) in the SETD2 gene, resulting in an arg1740-to-gln (R1740Q) substitution at a conserved residue in a region of unknown function. The mutation, which was found through clinical genetics services, was not present in the gnomAD database. The patients were ascertained through collaborative efforts, and the phenotype determined retrospectively. Functional studies of the variant and studies of patient cells were not performed. The patients had developmental delay with moderately impaired intellectual development, low-normal head circumference, variable and mild dysmorphic features, and absence of additional congenital anomalies or systemic involvement. The phenotype was considered to be different from that of patients with other mutations in the SETD2 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32710489" 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="Carrozza2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Carrozza, M. J., Li, B., Florens, L., Suganuma, T., Swanson, S. K., Lee, K. K., Shia, W.-J., Anderson, S., Yates, J., Washburn, M. P., Workman, J. L.
|
|
<strong>Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription.</strong>
|
|
Cell 123: 581-592, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16286007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16286007</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16286007" 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.2005.10.023" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Chen2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, M., Quan, Y., Duan, G., Wu, H., Bai, T., Wang, Y., Zhou, S., Ou, J., Shen, Y., Hu, Z., Xia, K., Guo, H.
|
|
<strong>Mutation pattern and genotype-phenotype correlations of SETD2 in neurodevelopmental disorders.</strong>
|
|
Europ. J. Med. Genet. 64: 104200, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33766796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33766796</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33766796" 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.ejmg.2021.104200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Faber1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Faber, P. W., Barnes, G. T., Srinidhi, J., Chen, J., Gusella, J. F., MacDonald, M. E.
|
|
<strong>Huntingtin interacts with a family of WW domain proteins.</strong>
|
|
Hum. Molec. Genet. 7: 1463-1474, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9700202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9700202</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9700202" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/7.9.1463" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Hacker2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hacker, K. E., Fahey, C. C., Shinsky, S. A., Chiang, Y. J., DiFiore, J. V., Jha, D. K., Vo, A. H., Shavit, J. A., Davis, I. J., Strahl, B. D., Rathmell, W. K.
|
|
<strong>Structure/function analysis of recurrent mutations in SETD2 protein reveals a critical and conserved role for a SET domain residue in maintaining protein stability and histone H3 lys-36 trimethylation.</strong>
|
|
J. Biol. Chem. 291: 21283-21295, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27528607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27528607</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27528607[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=27528607" 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.M116.739375" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Iossifov2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iossifov, I., O'Roak, B. J., Sanders, S. J., Ronemus, M., Krumm, N., Levy, D., Stessman, H. A., Vives, L., Patterson, K. E., Smith, J. D., Paeper, B., and 35 others.
|
|
<strong>The contribution of de novo coding mutations to autism spectrum disorder.</strong>
|
|
Nature 515: 216-221, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25363768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25363768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25363768[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=25363768" 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/nature13908" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Keogh2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Keogh, M.-C., Kurdistani, S. K., Morris, S. A., Ahn, S. H., Podolny, V., Collins, S. R., Schuldiner, M., Chin, K., Punna, T., Thompson, N. J., Boone, C., Emili, A., Weissman, J. S., Hughes, T. R., Strahl, B. D., Grunstein, M., Greenblatt, J. F., Buratowski, S., Krogan, N. J.
|
|
<strong>Cotranscriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.</strong>
|
|
Cell 123: 593-605, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16286008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16286008</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16286008" 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.2005.10.025" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Lumish2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lumish, H. S., Wynn, J., Devinsky, O., Chung, W. K.
|
|
<strong>SETD2 mutation in a child with autism, intellectual disabilities and epilepsy.</strong>
|
|
J. Autism Dev. Disord. 45: 3764-3770, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26084711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26084711</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26084711" 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/s10803-015-2484-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Luscan2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Luscan, A., Laurendeau, I., Malan, V., Francannet, C., Odent, S., Giuliano, F., Lacombe, D., Touraine, R., Vidaud, M., Pasmant, E., Cormier-Daire, V.
|
|
<strong>Mutations in SETD2 cause a novel overgrowth condition.</strong>
|
|
J. Med. Genet. 51: 512-517, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24852293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24852293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24852293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmedgenet-2014-102402" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Marzin2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marzin, P., Rondeau, S., Aldinger, K. A., Alessandri, J. L., Isidor, B., Heron, D., Keren, B., Dobyns, W. B., Cormier-Daire, V.
|
|
<strong>SETD2 related overgrowth syndrome: Presentation of four new patients and review of the literature.</strong>
|
|
Am. J. Med. Genet. 181C: 509-518, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31643139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31643139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31643139" 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.31746" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Nagase2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nagase, T., Kikuno, R., Hattori, A., Kondo, Y., Okumura, K., Ohara, O.
|
|
<strong>Prediction of the coding sequences of unidentified human genes, XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
|
|
DNA Res. 7: 347-355, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11214970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11214970</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11214970" 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/dnares/7.6.347" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="O'Roak2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others.
|
|
<strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong>
|
|
Science 338: 1619-1622, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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=23160955" 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.1227764" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="O'Roak2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
O'Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., Turner, E. H., Stanaway, I. B., and 11 others.
|
|
<strong>Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.</strong>
|
|
Nature 485: 246-250, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22495309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22495309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22495309[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=22495309" 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/nature10989" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Park2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Park, I. Y., Powell, R. T., Tripathi, D. N., Dere, R., Ho, T. H., Blasius, T. L., Chiang, Y. C., Davis, I. J., Fahey, C. C., Hacker, K. E., Verhey, K. J., Bedford, M. T., Jonasch, E., Rathmell, W. K., Walker, C. L.
|
|
<strong>Dual chromatin and cytoskeletal remodeling by SETD2.</strong>
|
|
Cell 166: 950-962, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27518565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27518565</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27518565[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=27518565" 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.2016.07.005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Rabin2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rabin, R., Radmanesh, A., Glass, I. A., Dobyns, W. B., Aldinger, K. A., Shieh, J. T., Romoser, S., Bombei, H., Dowsett, L., Trapane, P., Bernat, J. A., Baker, J., and 29 others.
|
|
<strong>Genotype-phenotype correlation at codon 1740 of SETD2.</strong>
|
|
Am. J. Med. Genet. 182A: 2037-2048, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32710489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32710489</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32710489" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.61724" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Rega2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rega, S., Stiewe, T., Chang, D.-I., Pollmeier, B., Esche, H., Bardenheuer, W., Marquitan, G., Putzer, B. M.
|
|
<strong>Identification of full-length huntingtin-interacting protein p231HBP/HYPB as a DNA-binding factor.</strong>
|
|
Molec. Cell. Neurosci. 18: 68-79, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11461154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11461154</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11461154" 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/mcne.2001.1004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Sun2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sun, X.-J., Wei, J., Wu, X.-Y., Hu, M., Wang, L., Wang, H.-H., Zhang, Q.-H., Chen, S.-J., Huang, Q.-H., Chen, Z.
|
|
<strong>Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase.</strong>
|
|
J. Biol. Chem. 280: 35261-35271, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16118227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16118227</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16118227" 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.M504012200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="van Rij2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van Rij, M. C., Hollink, I. H. I. M., Terhal, P. A., Kant, S. G., Ruivenkamp, C., van Haeringen, A., Kievit, J. A., van Belzen, M. J.
|
|
<strong>Two novel cases expanding the phenotype of SETD2-related overgrowth syndrome.</strong>
|
|
Am. J. Med. Genet. 176A: 1212-1215, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29681085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29681085</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29681085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.38666" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Xu2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Xu, Q., Xiang, Y., Wang, Q., Wang, L., Brind'Amour, J., Bogutz, A. B., Zhang, Y., Yu, G., Xia, W., Du, Z., Huang, C., and 12 others.
|
|
<strong>SETD2 regulates the maternal epigenome, genomic imprinting and embryonic development.</strong>
|
|
Nature Genet. 51: 844-856, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31040401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31040401</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31040401" 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/s41588-019-0398-7" 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 : 02/16/2023
|
|
</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">
|
|
Bao Lige - updated : 01/10/2023<br>Cassandra L. Kniffin - updated : 12/12/2022<br>Matthew B. Gross - updated : 07/02/2019<br>Bao Lige - updated : 07/02/2019<br>Nara Sobreira - updated : 2/24/2016
|
|
</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">
|
|
Patricia A. Hartz : 5/6/2009
|
|
</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">
|
|
carol : 07/18/2024
|
|
</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">
|
|
carol : 02/17/2023<br>carol : 02/16/2023<br>carol : 02/14/2023<br>mgross : 01/10/2023<br>alopez : 12/13/2022<br>ckniffin : 12/12/2022<br>mgross : 07/02/2019<br>mgross : 07/02/2019<br>carol : 10/21/2016<br>joanna : 02/24/2016<br>carol : 2/24/2016<br>carol : 2/24/2016<br>mgross : 2/5/2013<br>alopez : 3/11/2010<br>carol : 9/15/2009<br>mgross : 5/6/2009
|
|
</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> 612778
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SET DOMAIN-CONTAINING PROTEIN 2; SETD2
|
|
|
|
</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">
|
|
SET2<br />
|
|
HUNTINGTIN-INTERACTING PROTEIN B; HYPB<br />
|
|
HUNTINGTIN-BINDING PROTEIN, 231-KD; HBP231<br />
|
|
KIAA1732
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: SETD2</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 1300117002;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 3p21.31
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 3:47,016,436-47,164,840 </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="3">
|
|
<span class="mim-font">
|
|
3p21.31
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Intellectual developmental disorder, autosomal dominant 70
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
620157
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Luscan-Lumish syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
616831
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Rabin-Pappas syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
620155
|
|
</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>Methylation of histone H3 (see 602810) lys36 (H3K36) is associated with transcribed regions and functions in transcription fidelity, RNA splicing, and DNA repair. SETD2 is the primary methyltransferase catalyzing H3K36 trimethylation (H3K36me3) (summary by Xu et al., 2019) </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>Huntington disease (143100) is caused by expansion of a CAG trinucleotide repeat encoding an N-terminal polyglutamine region in huntingtin (HTT; 613004) to more than 34 units. Using N-terminal domains of HTT containing 58 or 62 glutamines in a yeast 2-hybrid assay of a fetal brain cDNA library, followed by database analysis and screening brain and testis cDNA libraries, Faber et al. (1998) obtained a partial SETD2 clone, which they called HYPB. The deduced protein has a WW domain. Northern blot analysis detected a transcript of about 9.0 kb that was variably expressed in all tissues examined. </p><p>By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (2000) cloned SETD2, which they designated KIAA1732. The deduced protein contains 1,325 amino acids. RT-PCR detected low SETD2 expression in all adult and fetal tissues and specific adult brain regions examined. </p><p>Using a yeast 1-hybrid screen of a HeLa cell cDNA library to identify proteins that could bind transcriptional start site-2 (TS2) of the adenovirus E1A gene, followed by RT-PCR of normal human foreskin fibroblasts, Rega et al. (2001) cloned full-length SETD2, which they called HBP231. The deduced 2,061-amino acid protein has a calculated molecular mass of about 231 kD. It has a putative N-terminal tyrosine phosphorylation site, a central SET domain, and a C-terminal WW/WWP domain that is followed by a putative nuclear localization signal. The C-terminal region of HBP231 corresponds to the HYPB sequence. Northern blot analysis detected a 7.5-kb transcript expressed at variable levels in all tissues examined. Western blot analysis of HeLa cells showed that HBP231 had an apparent molecular mass of 231 kD. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By FISH and genomic sequence analysis, Rega et al. (2001) mapped the SETD2 gene to chromosome 3p21.3-p21.2. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using a yeast 2-hybrid assay, Faber et al. (1998) showed that HYPB interacted with normal and mutant huntingtin in extracts of Huntington disease lymphoblastoid cells. The interaction was mediated by the WW domain region of HYPB and by the N-terminal proline-rich region in huntingtin, and it was enhanced by lengthening the adjacent glutamine tract. </p><p>Using electrophoretic mobility shift analysis with nuclear extracts of HeLa cells, Rega et al. (2001) confirmed that endogenous HBP231 bound the TS2 motif of the adenovirus E1A promoter in a sequence-specific manner. HBP231 expression was elevated in human embryonic kidney cells expressing E1A, suggesting that the observed autoactivation of E1A may be achieved by induced HBP231 expression. </p><p>Sun et al. (2005) showed that the SET domain and flanking AWS and postSET domains of human HBP231 mediated H3K36-specific histone methyltransferase activity. The isolated low-charged region of HBP231 immediately following the WW domain showed transcriptional activity, although a longer construct did not. A C-terminal fragment of HBP231 containing the AWS, SET, and postSET domains, the low-charged region, and the WW domain associated with hyperphosphorylated RNA polymerase II (see 180660), but not with the unphosphorylated form. Domain analysis revealed that the region C-terminal to the WW domain mediated the interaction of HBP231 with phosphorylated RNA polymerase II. Sun et al. (2005) concluded that HBP231 may coordinate histone methylation and transcriptional regulation. </p><p>The yeast histone deacetylase Rpd3 is recruited to promoters and represses transcription initiation. Carrozza et al. (2005) and Keogh et al. (2005) independently showed that the yeast SETD2 ortholog, Set2, is a histone H3K36 methyltransferase associated with a small Rpd3 complex that signals deacetylation of ORFs by Rpd3 and suppresses transcription initiation. </p><p>By immunoprecipitation and pull-down analyses, Park et al. (2016) showed that human SETD2 bound directly to alpha-tubulin (see 602529) in vitro through its SET domain to methylate alpha-tubulin at K40. Analysis in mouse embryonic fibroblasts (MEFs) indicated that microtubule methylation occurred during mitosis and cytokinesis, which could be completed through the catalytic activity of Setd2. Mass spectrometric analysis revealed that methylation of alpha-tubulin at K40 by SETD2 also occurred in vivo and identified SETD2 as a dual-function methyltransferase that directly methylated both histones and alpha-tubulin. Moreover, analysis of MEFs from Setd2 -/- mice showed that Setd2 was a mitotic microtubule methyltransferase, as methylation of microtubules was lost in Setd2 -/- MEFs. Setd2 was required for genomic stability and normal mitosis and cytokinesis, as Setd2 -/- MEFs displayed increase in ploidy and polynucleation, as well as elevated defects in mitosis and cytokinesis. Further analysis with human cells showed that loss of alpha-tubulin methylation by SETD2 caused mitotic and cytokinesis defects, confirming SETD2 as a dual-function methyltransferase for both chromatin and the cytoskeleton. </p><p>By bioinformatic analysis, Hacker et al. (2016) identified a high degree of structural and sequence homology between human SETD2 and its yeast ortholog, Set2, especially in their SET and SRI domains. Expression of SETD2 with SET domain mutations, which is found in some cancer cells, especially clear-cell renal cell carcinoma, in SETD2-deficient human cells revealed that different mutations differentially destabilized SETD2 and had separate effects on histone H3K36me3. One SET domain mutation, arg1625 to cys (R1625C), resulted in decreased RNA and a shortened protein half-life, and analysis with purified recombinant protein showed that loss of catalytic activity for this mutant was not due to protein misfolding or reduced thermal stability but rather to diminished substrate binding. Likewise, domain-specific mutations in Set2 resulted in different effects on H3K36 methylation status in yeast. However, in contrast with human cells, histone H3K36me2 was indispensable, whereas H3K36me3 was dispensable. Further analysis demonstrated that SETD2-mediated H3K36me3 in human cells was coupled to efficient resolution of double-strand breaks and the DNA damage response. </p><p>Using chromatin immunoprecipitation-sequencing analysis, Xu et al. (2019) showed that H3K36me3 correlated with DNA methylation in fully grown mouse oocytes. However, H3K36me3 was mutually exclusive with H3K4me3 and H3K27me3, and global H3K36me3 and H3K27me3 were unaffected in the absence of DNA methylation. Depletion of Setd2 in mouse oocytes resulted in reduced metaphase II oocyte number and sterility of female mice. H3K36me3 was lost in Setd2-deficient oocytes and led to alteration of the global DNA methylation level, redistribution of H3K4me3 and H3K27me3, and a subsequent change in chromatin accessibility. The redistribution of H3K27me3, but not H3K4me3, partially resulted in aberrant gene expression in Setd2-deficient oocytes. Setd2 promoted the establishment of maternal imprints, likely through H3K36me3-mediated recruitment of Dnmt3a (602769)/Dnmt3l (606588) and simultaneous inhibition of H3K4me3. As a result, maternal imprints and ectopic H3K4me3 at imprinting control regions were lost in Setd2-deficient oocytes. The authors found that maternal H3K36me3 was transiently inherited in early embryos after fertilization, just like H3K4me3 and H3K27me3 during early development. The defective maternal epigenome and aberrant gene expression observed in Setd2-deficient oocytes were inherited in 1-cell embryos after fertilization. Consequently, maternal depletion of Setd2 resulted in absence of maternal DNA replication and failure of zygotic genome activation and maternal RNA clearance, leading to 1-cell arrest after implantation and causing lethality of Setd2-deficient embryos. Further investigation demonstrated that both oocyte cytoplasm and chromatin defects contributed to lethality of Setd2-deficient embryos, and that Setd2-dependent patterning of the maternal epigenome was essential for postimplantation development. </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>Luscan-Lumish syndrome</em></strong></p><p>
|
|
O'Roak et al. (2012, 2012) sequenced a total of 677 individual exomes from 209 families from the autism spectrum disorder (ASD) Simons Simplex Collection (SSC) and identified 4 individuals with ASD and heterozygous mutations in the SETD2 gene: 2 with nonsense mutations (paternally-inherited C94X and maternally-inherited Q7X), 1 with a de novo I42F missense mutation, and 1 (patient 12565.p1) with a de novo frameshift mutation. Lumish et al. (2015) stated that the patient with the frameshift mutation (612778.0001) also had a history of failure to thrive, nonfebrile seizures starting at 4 years of age, motor delays, low-normal nonverbal IQ, and macrocephaly, termed Luscan-Lumish syndrome (LLS; 616831). </p><p>Iossifov et al. (2014) sequenced exomes from more than 2,500 simplex families, each having a child with ASD, and identified 2 unrelated individuals with mutations in the SETD2 gene, a 1-basepair deletion and a missense variant. Most of the families were from the ASD SSC. </p><p>In 2 'Sotos syndrome-like' patients, Luscan et al. (2014) identified heterozygous mutations in the SETD2 gene (612778.0002 and 612778.0003). Neither variant was reported in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. </p><p>By whole-exome sequencing in a 17-year-old girl with Luscan-Lumish syndrome, Lumish et al. (2015) identified a heterozygous de novo frameshift mutation (612778.0004) in the SETD2 gene. The mutation was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project database, in the dbSNP database, or in over 9,000 clinical exomes sequenced at GeneDx. </p><p>In 2 patients with intellectual disability, speech delay, autism spectrum disorder, and macrocephaly consistent with Luscan-Lumish syndrome, van Rij et al. (2018) identified de novo heterozygous frameshift mutations in the SETD2 gene (NM_014159.6). These included a deletion/insertion (c.1647_1667delinsAC) in exon 3 and a single base-pair deletion (c.6775delG) in exon 15, both resulting in a frameshift and a premature stop codon. The variants were not present in the unaffected parents of either patient. </p><p>In 4 patients with Luscan-Lumish syndrome, Marzin et al. (2019) identified 2 nonsense mutations (K1426X and Y2157X) and 2 missense mutations (Y1666C and R1625H) in the SETD2 gene (NM_014159.6), all of which were located in the catalytic domain SET2. In a review of their 4 patients and 9 previously reported patients with LLS, the authors found that the mutations were intragenic loss-of-function variants (69% truncating and 31% missense) distributed throughout the gene. </p><p>Using targeting sequencing in 2 patients with autism spectrum disorder and other features of Luscan-Lumish syndrome, Chen et al. (2021) identified 2 de novo mutations in the SETD2 gene (NM_014159): a splicing mutation (c.4715+1G-A) and a missense mutation (c.3185C-T, P1062L). Neither variant was reported in large public databases. The authors also evaluated 17 reported de novo SETD2 variants (8 frameshift, 1 nonsense, 7 missense, 1 in-frame deletion). All missense variants occurred at residues that were evolutionarily conserved. Using ACMG criteria, 13 of the 19 variants were classified as pathogenic, 5 as likely pathogenic, and one (missense) as a variant of uncertain significance. </p><p><strong><em>Rabin-Pappas Syndrome</em></strong></p><p>
|
|
In 12 unrelated patients (group 1) with Rabin-Pappas syndrome (RAPAS; 620155), Rabin et al. (2020) identified a de novo heterozygous missense mutation in the SETD2 gene (R1740W; 612778.0005). The mutation, which was found through clinical genetics services, was not present in the gnomAD database. The patients were ascertained through collaborative efforts, and the phenotype determined retrospectively. Functional studies of the variant and studies of patient cells were not performed. The patients had a severe phenotype with intellectual disability, inability to walk or speak, and involvement of multiple organ systems, which was considered to be different from that of patients with other mutations in SETD2 gene, including those with a different mutation at the same codon (R1740Q; 612778.0006). </p><p><strong><em>Intellectual Developmental Disorder 70, Autosomal Dominant</em></strong></p><p>
|
|
In 3 unrelated patients (group 2) with autosomal dominant intellectual developmental disorder-70 (MRD70; 620157), Rabin et al. (2020) identified a de novo heterozygous missense mutation in the SETD2 gene (R1740Q; 612778.0006). The mutation, which was found through clinical genetics services, was not present in the gnomAD database. The patients were ascertained through collaborative efforts, and the phenotype determined retrospectively. Functional studies of the variant and studies of patient cells were not performed. The patients had developmental delay with moderately impaired intellectual development, low-normal head circumference, variable and mild dysmorphic features, and absence of additional congenital anomalies or systemic involvement. The phenotype was considered to be different from that of patients with other mutations in the SETD2 gene, including those with a different mutation at the same codon (R1740W; 612778.0005). </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 LUSCAN-LUMISH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SETD2, 1-BP DEL, 6341A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs869025569,
|
|
|
|
|
|
|
|
ClinVar: RCV000208546
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By exome sequencing of patients from the Simons Simplex Collection, O'Roak et al. (2012) identified a de novo heterozygous 1-bp deletion (c.6341delA, NM_014159) in the SETD2 gene, resulting in a frameshift (Asn2114IlefsTer33) in a female (patient 12565.p1) with autism spectrum disorder. Lumish et al. (2015) stated that this patient also had failure to thrive, seizures, motor delay, low-normal IQ, and macrocephaly (Luscan-Lumish syndrome, 616831). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 LUSCAN-LUMISH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SETD2, LEU1815TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs869025570,
|
|
|
|
|
|
|
|
ClinVar: RCV000208561
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 26-year-old French man with Luscan-Lumish syndrome (LLS; 616831), who was diagnosed with a 'Sotos-like syndrome,' Luscan et al. (2014) identified a de novo heterozygous c.5444T-G transversion (c.5444T-G, NM_014159.6) in the SETD2 gene, resulting in a leu1815-to-trp (L1815W) substitution at a conserved residue. The mutation was not found in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 LUSCAN-LUMISH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SETD2, GLN274TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs869025571,
|
|
|
|
|
|
|
|
ClinVar: RCV000208536
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 23-year-old woman with Luscan-Lumish syndrome (LLS; 616831), who was diagnosed with 'Sotos-like syndrome,' Luscan et al. (2014) identified a heterozygous c.820C-T transition (c.820C-T, NM_014159.6), resulting in a gln274-to-ter (Q274X) substitution. The woman was adopted and her biologic parents could not be tested. The mutation was not found in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 LUSCAN-LUMISH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SETD2, 1-BP DEL, 2028T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs869025572,
|
|
|
|
|
|
|
|
ClinVar: RCV000208551
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By whole-exome sequencing in a 17-year-old girl with Luscan-Lumish syndrome (LLS; 616831), Lumish et al. (2015) identified a heterozygous de novo 1-bp deletion (c.2028delT, NM_014159.6) in the SETD2 gene, resulting in a frameshift (Pro677LeufsTer19). This mutations was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project database, in the dbSNP database, or in over 9,000 clinical exomes sequenced at GeneDx. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 RABIN-PAPPAS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SETD2, ARG1740TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1057523157,
|
|
|
|
|
|
|
|
ClinVar: RCV000426759, RCV000779643, RCV000853394, RCV001258009, RCV001267453, RCV001267684, RCV002467447, RCV004554776
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 12 unrelated patients (group 1) with Rabin-Pappas syndrome (RAPAS; 620155), Rabin et al. (2020) identified a de novo heterozygous c.5218C-T transition (c.5218C-T, NM_014159.6) in the SETD2 gene, resulting in an arg1740-to-trp (R1740W) substitution at conserved residue in a region of unknown function. The mutation, which was found through clinical genetics services, was not present in the gnomAD database. The patients were ascertained through collaborative efforts, and the phenotype determined retrospectively. Functional studies of the variant and studies of patient cells were not performed. The patients had a severe phenotype with intellectual disability, inability to walk or speak, and involvement of multiple organ systems, which was considered to be different from that of patients with other SETD2 mutations. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 70</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SETD2, ARG1740GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2107651195,
|
|
|
|
|
|
|
|
ClinVar: RCV001823014, RCV002259402, RCV002467456
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 unrelated patients (group 2) with autosomal dominant intellectual developmental disorder-70 (MRD70; 620157), Rabin et al. (2020) identified a de novo heterozygous c.5219G-A transition (c.5219G-A, NM_014159.6) in the SETD2 gene, resulting in an arg1740-to-gln (R1740Q) substitution at a conserved residue in a region of unknown function. The mutation, which was found through clinical genetics services, was not present in the gnomAD database. The patients were ascertained through collaborative efforts, and the phenotype determined retrospectively. Functional studies of the variant and studies of patient cells were not performed. The patients had developmental delay with moderately impaired intellectual development, low-normal head circumference, variable and mild dysmorphic features, and absence of additional congenital anomalies or systemic involvement. The phenotype was considered to be different from that of patients with other mutations in the SETD2 gene. </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">
|
|
Carrozza, M. J., Li, B., Florens, L., Suganuma, T., Swanson, S. K., Lee, K. K., Shia, W.-J., Anderson, S., Yates, J., Washburn, M. P., Workman, J. L.
|
|
<strong>Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription.</strong>
|
|
Cell 123: 581-592, 2005.
|
|
|
|
|
|
[PubMed: 16286007]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2005.10.023]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, M., Quan, Y., Duan, G., Wu, H., Bai, T., Wang, Y., Zhou, S., Ou, J., Shen, Y., Hu, Z., Xia, K., Guo, H.
|
|
<strong>Mutation pattern and genotype-phenotype correlations of SETD2 in neurodevelopmental disorders.</strong>
|
|
Europ. J. Med. Genet. 64: 104200, 2021.
|
|
|
|
|
|
[PubMed: 33766796]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ejmg.2021.104200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Faber, P. W., Barnes, G. T., Srinidhi, J., Chen, J., Gusella, J. F., MacDonald, M. E.
|
|
<strong>Huntingtin interacts with a family of WW domain proteins.</strong>
|
|
Hum. Molec. Genet. 7: 1463-1474, 1998.
|
|
|
|
|
|
[PubMed: 9700202]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/7.9.1463]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hacker, K. E., Fahey, C. C., Shinsky, S. A., Chiang, Y. J., DiFiore, J. V., Jha, D. K., Vo, A. H., Shavit, J. A., Davis, I. J., Strahl, B. D., Rathmell, W. K.
|
|
<strong>Structure/function analysis of recurrent mutations in SETD2 protein reveals a critical and conserved role for a SET domain residue in maintaining protein stability and histone H3 lys-36 trimethylation.</strong>
|
|
J. Biol. Chem. 291: 21283-21295, 2016.
|
|
|
|
|
|
[PubMed: 27528607]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M116.739375]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iossifov, I., O'Roak, B. J., Sanders, S. J., Ronemus, M., Krumm, N., Levy, D., Stessman, H. A., Vives, L., Patterson, K. E., Smith, J. D., Paeper, B., and 35 others.
|
|
<strong>The contribution of de novo coding mutations to autism spectrum disorder.</strong>
|
|
Nature 515: 216-221, 2014.
|
|
|
|
|
|
[PubMed: 25363768]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature13908]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Keogh, M.-C., Kurdistani, S. K., Morris, S. A., Ahn, S. H., Podolny, V., Collins, S. R., Schuldiner, M., Chin, K., Punna, T., Thompson, N. J., Boone, C., Emili, A., Weissman, J. S., Hughes, T. R., Strahl, B. D., Grunstein, M., Greenblatt, J. F., Buratowski, S., Krogan, N. J.
|
|
<strong>Cotranscriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.</strong>
|
|
Cell 123: 593-605, 2005.
|
|
|
|
|
|
[PubMed: 16286008]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2005.10.025]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lumish, H. S., Wynn, J., Devinsky, O., Chung, W. K.
|
|
<strong>SETD2 mutation in a child with autism, intellectual disabilities and epilepsy.</strong>
|
|
J. Autism Dev. Disord. 45: 3764-3770, 2015.
|
|
|
|
|
|
[PubMed: 26084711]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10803-015-2484-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Luscan, A., Laurendeau, I., Malan, V., Francannet, C., Odent, S., Giuliano, F., Lacombe, D., Touraine, R., Vidaud, M., Pasmant, E., Cormier-Daire, V.
|
|
<strong>Mutations in SETD2 cause a novel overgrowth condition.</strong>
|
|
J. Med. Genet. 51: 512-517, 2014.
|
|
|
|
|
|
[PubMed: 24852293]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2014-102402]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marzin, P., Rondeau, S., Aldinger, K. A., Alessandri, J. L., Isidor, B., Heron, D., Keren, B., Dobyns, W. B., Cormier-Daire, V.
|
|
<strong>SETD2 related overgrowth syndrome: Presentation of four new patients and review of the literature.</strong>
|
|
Am. J. Med. Genet. 181C: 509-518, 2019.
|
|
|
|
|
|
[PubMed: 31643139]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.c.31746]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nagase, T., Kikuno, R., Hattori, A., Kondo, Y., Okumura, K., Ohara, O.
|
|
<strong>Prediction of the coding sequences of unidentified human genes, XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
|
|
DNA Res. 7: 347-355, 2000.
|
|
|
|
|
|
[PubMed: 11214970]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/dnares/7.6.347]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others.
|
|
<strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong>
|
|
Science 338: 1619-1622, 2012.
|
|
|
|
|
|
[PubMed: 23160955]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1227764]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
O'Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., Turner, E. H., Stanaway, I. B., and 11 others.
|
|
<strong>Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.</strong>
|
|
Nature 485: 246-250, 2012.
|
|
|
|
|
|
[PubMed: 22495309]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10989]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Park, I. Y., Powell, R. T., Tripathi, D. N., Dere, R., Ho, T. H., Blasius, T. L., Chiang, Y. C., Davis, I. J., Fahey, C. C., Hacker, K. E., Verhey, K. J., Bedford, M. T., Jonasch, E., Rathmell, W. K., Walker, C. L.
|
|
<strong>Dual chromatin and cytoskeletal remodeling by SETD2.</strong>
|
|
Cell 166: 950-962, 2016.
|
|
|
|
|
|
[PubMed: 27518565]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2016.07.005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rabin, R., Radmanesh, A., Glass, I. A., Dobyns, W. B., Aldinger, K. A., Shieh, J. T., Romoser, S., Bombei, H., Dowsett, L., Trapane, P., Bernat, J. A., Baker, J., and 29 others.
|
|
<strong>Genotype-phenotype correlation at codon 1740 of SETD2.</strong>
|
|
Am. J. Med. Genet. 182A: 2037-2048, 2020.
|
|
|
|
|
|
[PubMed: 32710489]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.61724]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rega, S., Stiewe, T., Chang, D.-I., Pollmeier, B., Esche, H., Bardenheuer, W., Marquitan, G., Putzer, B. M.
|
|
<strong>Identification of full-length huntingtin-interacting protein p231HBP/HYPB as a DNA-binding factor.</strong>
|
|
Molec. Cell. Neurosci. 18: 68-79, 2001.
|
|
|
|
|
|
[PubMed: 11461154]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/mcne.2001.1004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sun, X.-J., Wei, J., Wu, X.-Y., Hu, M., Wang, L., Wang, H.-H., Zhang, Q.-H., Chen, S.-J., Huang, Q.-H., Chen, Z.
|
|
<strong>Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase.</strong>
|
|
J. Biol. Chem. 280: 35261-35271, 2005.
|
|
|
|
|
|
[PubMed: 16118227]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M504012200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van Rij, M. C., Hollink, I. H. I. M., Terhal, P. A., Kant, S. G., Ruivenkamp, C., van Haeringen, A., Kievit, J. A., van Belzen, M. J.
|
|
<strong>Two novel cases expanding the phenotype of SETD2-related overgrowth syndrome.</strong>
|
|
Am. J. Med. Genet. 176A: 1212-1215, 2018.
|
|
|
|
|
|
[PubMed: 29681085]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.38666]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Xu, Q., Xiang, Y., Wang, Q., Wang, L., Brind'Amour, J., Bogutz, A. B., Zhang, Y., Yu, G., Xia, W., Du, Z., Huang, C., and 12 others.
|
|
<strong>SETD2 regulates the maternal epigenome, genomic imprinting and embryonic development.</strong>
|
|
Nature Genet. 51: 844-856, 2019.
|
|
|
|
|
|
[PubMed: 31040401]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41588-019-0398-7]
|
|
|
|
|
|
</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 : 02/16/2023<br>Bao Lige - updated : 01/10/2023<br>Cassandra L. Kniffin - updated : 12/12/2022<br>Matthew B. Gross - updated : 07/02/2019<br>Bao Lige - updated : 07/02/2019<br>Nara Sobreira - updated : 2/24/2016
|
|
</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">
|
|
Patricia A. Hartz : 5/6/2009
|
|
</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">
|
|
carol : 07/18/2024<br>carol : 02/17/2023<br>carol : 02/16/2023<br>carol : 02/14/2023<br>mgross : 01/10/2023<br>alopez : 12/13/2022<br>ckniffin : 12/12/2022<br>mgross : 07/02/2019<br>mgross : 07/02/2019<br>carol : 10/21/2016<br>joanna : 02/24/2016<br>carol : 2/24/2016<br>carol : 2/24/2016<br>mgross : 2/5/2013<br>alopez : 3/11/2010<br>carol : 9/15/2009<br>mgross : 5/6/2009
|
|
</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>
|
|
|
|
|