4578 lines
388 KiB
Text
4578 lines
388 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
|
|
|
|
- *603136 - CULLIN 3; CUL3
|
|
|
|
|
|
- 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=603136"><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">*603136</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="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/603136">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=ENSG00000036257;t=ENST00000264414" 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=8452" 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=603136" 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=ENSG00000036257;t=ENST00000264414" 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_001257197,NM_001257198,NM_003590,XM_006712800,XM_011511995,XM_011511996,XM_047446024" 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_003590" 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=603136" 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=09123&isoform_id=09123_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/CUL3" 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/1381146,3139079,3360457,3639052,4503165,12643396,24660078,32425427,33286088,62204956,62702365,62988770,119591234,119591235,119591236,158255738,221042818,380714663,380714665,767920144,767920148,767920150,929654395,2217331493,2462577778,2462577780,2462577782,2462577784" 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/Q13618" 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=8452" 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=ENSG00000036257;t=ENST00000264414" 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=CUL3" 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=CUL3" 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+8452" 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/CUL3" 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:8452" 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/8452" 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=chr2&hgg_gene=ENST00000264414.9&hgg_start=224470150&hgg_end=224585363&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:2553" 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:2553" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/cul3" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603136[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=603136[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/CUL3/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/ENSG00000036257" 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=CUL3" 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=CUL3" 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=CUL3" 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=CUL3&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/PA27049" 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:2553" 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/FBgn0261268.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:1347360" 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/CUL3#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:1347360" 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/8452/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=8452" 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=WBGene00000838;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-030131-3376" 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:8452" 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=CUL3&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
603136
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CULLIN 3; CUL3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CUL3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CUL3</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/2/1065?start=-3&limit=10&highlight=1065">2q36.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:224470150-224585363&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'})">2:224,470,150-224,585,363</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=619239,614496" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/1065?start=-3&limit=10&highlight=1065">
|
|
2q36.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Neurodevelopmental disorder with or without autism or seizures
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/619239"> 619239 </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">
|
|
Pseudohypoaldosteronism, type IIE
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/614496"> 614496 </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/603136" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/603136" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The CUL3 gene encodes a scaffolding component of the Cullin-RING ligase (CRL) complex, which belongs to a class of E3 ubiquitin ligases that mediate polyubiquitination of specific target proteins destined for degradation (summary by <a href="#16" class="mim-tip-reference" title="Nakashima, M., Kato, M., Matsukura, M., Kira, R., Ngu, L.-H., Lichtenbelt, K. D., van Gassen, K. L. I., Mitsuhashi, S., Saitsu, H., Matsumoto, N. <strong>De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms.</strong> J. Hum. Genet. 65: 727-734, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32341456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32341456</a>] [<a href="https://doi.org/10.1038/s10038-020-0758-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32341456">Nakashima et al., 2020</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32341456" 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>CUL3 is a component of a ubiquitin E3 ligase that is essential for mitotic division (<a href="#19" class="mim-tip-reference" title="Sumara, I., Quadroni, M., Frei, C., Olma, M. H., Sumara, G., Ricci, R., Peter, M. <strong>A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells.</strong> Dev. Cell 12: 887-900, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17543862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17543862</a>] [<a href="https://doi.org/10.1016/j.devcel.2007.03.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17543862">Sumara et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17543862" 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><a href="#11" class="mim-tip-reference" title="Kipreos, E. T., Lander, L. E., Wing, J. P., He, W. W., Hedgecock, E. M. <strong>cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family.</strong> Cell 85: 829-839, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8681378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8681378</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81267-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8681378">Kipreos et al. (1996)</a> identified a conserved gene family, designated cullins (see CUL1, <a href="/entry/603134">603134</a>), with at least 5 members in nematodes, 6 in humans, and 3 in S. cerevisiae. Human CUL3 is an ortholog of nematode cul3. <a href="#15" class="mim-tip-reference" title="Michel, J. J., Xiong, Y. <strong>Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A.</strong> Cell Growth Differ. 9: 435-449, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9663463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9663463</a>]" pmid="9663463">Michel and Xiong (1998)</a> identified human CUL3 cDNAs and reported that the predicted protein is 768 amino acids long. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9663463+8681378" 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 isolated from a size-fractionated human brain cDNA library, <a href="#8" class="mim-tip-reference" title="Ishikawa, K., Nagase, T., Suyama, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong> DNA Res. 5: 169-176, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9734811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9734811</a>] [<a href="https://doi.org/10.1093/dnares/5.3.169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9734811">Ishikawa et al. (1998)</a> isolated CUL3, which they designated KIAA0617. The deduced protein contains 768 amino acids. RT-PCR analysis detected highest CUL3 expression in ovary, followed by skeletal muscle and brain. Weaker expression was detected in heart, lung, liver, kidney, and testis, with little to no expression in other tissues examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9734811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Du, M., Sansores-Garcia, L., Zu, Z., Wu, K. K. <strong>Cloning and expression analysis of a novel salicylate suppressible gene, Hs-CUL-3, a member of cullin/Cdc53 family.</strong> J. Biol. Chem. 273: 24289-24292, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9733711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9733711</a>] [<a href="https://doi.org/10.1074/jbc.273.38.24289" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9733711">Du et al. (1998)</a> identified CUL3 as a gene whose expression in human fibroblasts was induced by phorbol 12-myristate 13-acetate (PMA) and suppressed by salicylate. They reported that the sequences of the human and C. elegans cul3 proteins share 46% identity. Northern blot analysis revealed that CUL3 is expressed as major 2.8- and minor 4.3-kb transcripts in various human tissues, with the highest levels in skeletal muscle and heart. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9733711" 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 analysis of a radiation hybrid panel, <a href="#8" class="mim-tip-reference" title="Ishikawa, K., Nagase, T., Suyama, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong> DNA Res. 5: 169-176, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9734811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9734811</a>] [<a href="https://doi.org/10.1093/dnares/5.3.169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9734811">Ishikawa et al. (1998)</a> mapped the CUL3 gene to human chromosome 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9734811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Hartz, P. A. <strong>Personal Communication.</strong> Baltimore, Md. 3/14/2012."None>Hartz (2012)</a> mapped the CUL3 gene to chromosome 2q36.2 based on an alignment of the CUL3 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF062537" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF062537</a>) with the genomic sequence (GRCh37).</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><a href="#19" class="mim-tip-reference" title="Sumara, I., Quadroni, M., Frei, C., Olma, M. H., Sumara, G., Ricci, R., Peter, M. <strong>A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells.</strong> Dev. Cell 12: 887-900, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17543862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17543862</a>] [<a href="https://doi.org/10.1016/j.devcel.2007.03.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17543862">Sumara et al. (2007)</a> found that KLHL9 (<a href="/entry/611201">611201</a>), KLHL13 (<a href="/entry/300655">300655</a>), and CUL3 interacted directly in a 370-kD protein complex in HeLa cell lysates. The CUL3/KLHL9/KLHL13 complex was the minimum unit required for correct chromosome alignment in metaphase, proper midzone and midbody formation, and completion of cytokinesis. CUL3/KLHL9/KLHL13 acted as an E3 ligase and regulated dynamic localization of the chromosomal passenger complex (CPC) protein Aurora B (AURKB; <a href="/entry/604970">604970</a>) on mitotic chromosomes and accumulation of Aurora B on the central spindle after anaphase onset. Aurora B directly bound the substrate-recognition domains of KLHL9 and KLHL13 in vitro and coimmunoprecipitated with the CUL3/KLHL9/KLHL13 complex during mitosis. Moreover, Aurora B was ubiquitylated in a CUL3-dependent manner in vivo and by reconstituted CUL3/KLHL9/KLHL13 in vitro. <a href="#19" class="mim-tip-reference" title="Sumara, I., Quadroni, M., Frei, C., Olma, M. H., Sumara, G., Ricci, R., Peter, M. <strong>A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells.</strong> Dev. Cell 12: 887-900, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17543862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17543862</a>] [<a href="https://doi.org/10.1016/j.devcel.2007.03.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17543862">Sumara et al. (2007)</a> concluded that CUL3/KLHL9/KLHL13 is an E3 ligase that controls the dynamic behavior of Aurora B on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17543862" 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 mass spectrometric analysis, <a href="#13" class="mim-tip-reference" title="Maerki, S., Olma, M. H., Staubli, T., Steigemann, P., Gerlich, D. W., Quadroni, M., Sumara, I., Peter, M. <strong>The Cul3-KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis.</strong> J. Cell Biol. 187: 791-800, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19995937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19995937</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19995937[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1083/jcb.200906117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19995937">Maerki et al. (2009)</a> found that KLHL21 (<a href="/entry/616262">616262</a>) and KLHL22 (<a href="/entry/618020">618020</a>) immunoprecipitated with CUL3, KLHL9, and KLHL13 from HeLa cell lysates. KLHL21 also interacted with Aurora B. Deletion analysis revealed that the BTB domain of KLHL21 was required for interaction with CUL3. Time-lapse microscopy revealed that knockdown of KLHL21 or KLHL22 via small interfering RNA delayed prometaphase and led to failure of proper metaphase plate formation. Knockdown of KLHL21, but not KLHL22, also caused multinucleation and failure of cytokinesis in a large number of cells. During anaphase, loss of KLHL21 inhibited translocation of Aurora B from segregating chromosomes to the spindle midzone and caused loss of CUL3 localization at the midzone. Likewise, knockdown of CUL3 caused loss of KLHL21 from the midzone. Sucrose gradient and gel filtration experiments revealed that KLHL21 and KLHL9 fractionated into overlapping but distinct CUL3 complexes, suggesting that KLHL21, KLHL9, and KLHL13 assemble distinct CUL3 complexes to regulate CPC localization during mitosis. CUL3-KLHL21 complexes also ubiquitinated Aurora B in vitro. <a href="#13" class="mim-tip-reference" title="Maerki, S., Olma, M. H., Staubli, T., Steigemann, P., Gerlich, D. W., Quadroni, M., Sumara, I., Peter, M. <strong>The Cul3-KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis.</strong> J. Cell Biol. 187: 791-800, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19995937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19995937</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19995937[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1083/jcb.200906117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19995937">Maerki et al. (2009)</a> concluded that different CUL3 complexes with KLHL9, KLHL13, and KLHL21 may target different pools of Aurora B for mitotic progression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19995937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Rondou, P., Haegeman, G., Vanhoenacker, P., Van Craenenbroeck, K. <strong>BTB protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase.</strong> J. Biol. Chem. 283: 11083-11096, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18303015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18303015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18303015[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.M708473200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18303015">Rondou et al. (2008)</a> showed that interaction between KLHL12 (<a href="/entry/614522">614522</a>) and the CUL3 ubiquitin ligase complex directed ubiquitination of dopamine receptor D4 (DRD4; <a href="/entry/126452">126452</a>). KLHL12 interacted directly with CUL3 and with the polymorphic intracellular loop-3 of D4. Knockdown of KLHL12 in KLHL12-overexpressing HEK293 cells abolished association of D4 with CUL3, and knockdown of CUL3 decreased ubiquitination of D4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18303015" 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 yeast 2-hybrid and immunoprecipitation analyses, <a href="#3" class="mim-tip-reference" title="Cummings, C. M., Bentley, C. A., Perdue, S. A., Baas, P. W., Singer, J. D. <strong>The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal mitosis in mammalian cells.</strong> J. Biol. Chem. 284: 11663-11675, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19261606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19261606</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19261606[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.M809374200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19261606">Cummings et al. (2009)</a> showed that human KLHDC5 (KLHL42; <a href="/entry/618919">618919</a>) and CUL3 physically interacted through the BTB domain of KLHDC5. Overexpression of KLHDC5 in HeLa cells stabilized microtubules and inhibited microtubule depolymerization required for normal cell morphology and mitosis, resulting in cells with multiple nuclei. In contrast, knockdown of KLHDC5 caused a dramatic loss of microtubule structure. Like KLHDC5, the microtubule-severing protein p60 (KATNA1; <a href="/entry/606696">606696</a>) was also expressed in mitotic cells, and its levels in were regulated by KLHDC5. p60 interacted with both CUL3 and KLHDC5, and at least 1 of the 3 kelch domains of KLHDC5 was required for the interaction. KLHDC5 served as a substrate recognition adaptor to recruit p60 to the CUL3-KLHDC5 complex, and CUL3 facilitated ubiquitination of p60 to mediate its degradation. CUL3 regulation of p60 abundance was vital for faithful progression of mitosis, as knockdown of CUL3 in HeLa cells increased p60 levels and resulted in accumulation of multinucleated cells due to their inability to complete cytokinesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19261606" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Jin, L., Pahuja, K. B., Wickliffe, K. E., Gorur, A., Baumgartel, C., Schekman, R., Rape, M. <strong>Ubiquitin-dependent regulation of COPII coat size and function.</strong> Nature 482: 495-500, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22358839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22358839</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22358839[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/nature10822" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22358839">Jin et al. (2012)</a> found that depletion of either Klhl12 or Cul3 in mouse embryonic stem cells resulted in cell compaction and delayed proliferation. Depletion of Cul3 in mouse fibroblasts had a much weaker effect. Overexpression and depletion studies showed that interaction of Klhl12 with Cul3 was required for monoubiquitination of the coat protein complex II (COPII) component Sec31 (see <a href="/entry/610257">610257</a>). Overexpression of Klhl12 resulted in expansion of the diameter of Sec31-containing COPII vesicles, and this expansion was required for transport and secretion of large cargo proteins, such as procollagens (see <a href="/entry/120150">120150</a>). A Sec31-binding mutant of Klhl12 neither colocalized with Sec31 nor induced formation of large vesicles. Disruption of KLHL12-CUL3 function in human HT1080 fibrosarcoma cells impaired COPII vesicle expansion and collagen export, but it had no effect on export of smaller cargo by small COPII vesicles. <a href="#10" class="mim-tip-reference" title="Jin, L., Pahuja, K. B., Wickliffe, K. E., Gorur, A., Baumgartel, C., Schekman, R., Rape, M. <strong>Ubiquitin-dependent regulation of COPII coat size and function.</strong> Nature 482: 495-500, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22358839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22358839</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22358839[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/nature10822" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22358839">Jin et al. (2012)</a> concluded that KLHL12-CUL3 monoubiquitination of SEC31 is required for COPII vesicle expansion to accommodate large or bulky cargo molecules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22358839" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Mathew, R., Seiler, M. P., Scanlon, S. T., Mao, A., Constantinides, M. G., Bertozzi-Villa, C., Singer, J. D., Bendelac, A. <strong>BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs.</strong> Nature 491: 618-621, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086144[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/nature11548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086144">Mathew et al. (2012)</a> reported that PLZF is prominently associated with CUL3 in natural killer T cell thymocytes. PLZF transports CUL3 to the nucleus, where the 2 proteins are associated within a chromatin modifying complex. Furthermore, PLZF expression results in selective ubiquitination changes of several components of this complex. CUL3 was also found associated with the BTB-ZF transcription factor BCL6 (<a href="/entry/109565">109565</a>), which directs the germinal center B cell and follicular T-helper cell programs. Conditional CUL3 deletion in mice demonstrated an essential role for CUL3 in the development of PLZF- and BCL6-dependent lineages. <a href="#14" class="mim-tip-reference" title="Mathew, R., Seiler, M. P., Scanlon, S. T., Mao, A., Constantinides, M. G., Bertozzi-Villa, C., Singer, J. D., Bendelac, A. <strong>BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs.</strong> Nature 491: 618-621, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086144[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/nature11548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23086144">Mathew et al. (2012)</a> concluded that distinct lineage-specific BTB-ZF transcription factors recruit CUL3 to alter the ubiquitination pattern of their associated chromatin-modifying complex. They proposed that this function is essential to direct the differentiation of several T- and B-cell effector programs, and may also be involved in the oncogenic role of PLZF and BCL6 in leukemias and lymphomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23086144" 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>KBTBD8 (<a href="/entry/616607">616607</a>) functions as an adaptor for substrate recognition by CUL3. Using mass spectrometric analysis, <a href="#22" class="mim-tip-reference" title="Werner, A., Iwasaki, S., McGourty, C. A., Medina-Ruiz, S., Teerikorpi, N., Fedrigo, I., Ingolia, N. T., Rape, M. <strong>Cell-fate determination by ubiquitin-dependent regulation of translation.</strong> Nature 525: 523-527, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26399832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26399832</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26399832[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/nature14978" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26399832">Werner et al. (2015)</a> found that KBTBD8 interacted with TCOF1 (<a href="/entry/606847">606847</a>) and NOLC1 (<a href="/entry/602394">602394</a>). CUL3-KBTBD8 monoubiquitinated TCOF1 and NOLC1 in a manner that required the cofactor beta-arrestin (see <a href="/entry/107940">107940</a>). Knockdown of KBTBD8, TCOF1, or NOLC1 in human embryonic stem cells (hESCs) via short hairpin RNA inhibited hESC differentiation into neural crest cells and accelerated hESC differentiation into central nervous system (CNS) precursors. Affinity purification revealed that ubiquitinated TCOF1-NOLC1 complexes engaged RNA polymerase I into complexes with the small ribosomal processing complex. <a href="#22" class="mim-tip-reference" title="Werner, A., Iwasaki, S., McGourty, C. A., Medina-Ruiz, S., Teerikorpi, N., Fedrigo, I., Ingolia, N. T., Rape, M. <strong>Cell-fate determination by ubiquitin-dependent regulation of translation.</strong> Nature 525: 523-527, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26399832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26399832</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26399832[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/nature14978" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26399832">Werner et al. (2015)</a> hypothesized that KBTBD8-dependent ubiquitination drives formation of a TCOF1-NOLC1 platform in hESCs that connects RNA polymerase I with ribosome modification enzymes at specific mRNAs to delay accumulation of CNS precursor proteins until neural crest specification has occurred. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26399832" 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 coimmunoprecipitation and mass spectrometric analyses, <a href="#23" class="mim-tip-reference" title="Zhang, C., Liu, J., Huang, G., Zhao, Y., Yue, X., Wu, H., Li, J., Zhu, J., Shen, Z., Haffty, B. G., Hu, W., Feng, Z. <strong>Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression.</strong> Genes Dev. 30: 1956-1970, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27664236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27664236</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27664236[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.283283.116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27664236">Zhang et al. (2016)</a> showed that ACLY (<a href="/entry/108728">108728</a>) interacted indirectly with CUL3 through KLHL25 (<a href="/entry/619893">619893</a>) to form a complex in human lung cancer H1299 cells. KLHL25 interacted directly with ACLY and functioned as a substrate adaptor to bridge ACLY to CUL3. CUL3-KLHL25 negatively regulated ACLY protein levels in cells through protein ubiquitination and degradation, and low CUL3 expression was associated with high ACLY expression in human lung cancer. Through negative regulation of ACLY, CUL3-KLHL25 reduced acetyl-CoA levels and inhibited lipid synthesis, which in turn contributed to the inhibitory effect of CUL3-KLHL25 on proliferation and anchorage-independent growth of lung cancer cells. In vivo analysis revealed that CUL3-KLHL25 inhibited growth of xenograft lung tumors in mice through negative regulation of ACLY. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27664236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Tian, M., Hao, F., Jin, X., Sun, X., Jiang, Y., Wang, Y., Li, D., Chang, T., Zou, Y., Peng, P., Xia, C., Liu, J., Li, Y., Wang, P., Feng, Y., Wei, M. <strong>ACLY ubiquitination by CUL3-KLHL25 induces the reprogramming of fatty acid metabolism to facilitate iTreg differentiation.</strong> eLife 10: e62394, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34491895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34491895</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34491895[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/10.7554/eLife.62394" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34491895">Tian et al. (2021)</a> found that Acly regulated differentiation of mouse inducible regulatory T cells (iTregs). Tgfb1 (<a href="/entry/190180">190180</a>) induced Acly downregulation through Cul3-Klhl25-mediated ubiquitination and degradation, which in turn facilitated iTreg differentiation. Analysis with human iTregs confirmed the conserved role of CUL3-KLHL25-mediated ACLY ubiquitination in iTreg differentiation. Analysis with a mouse inflammatory bowel disease (IBD; see <a href="/entry/266600">266600</a>) model revealed an important role of Cul3-Klhl25-mediated Acly ubiquitination in colitis alleviation and in regulation of diarrhea. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34491895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., Tan, Y., Ci, Y., Wu, F., Dai, X., Guo, J., Huang, Y.-H., Fan, C., Ren, S., Sun, Y., Freeman, G. J., Sicinski, P., Wei, W. <strong>Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance.</strong> Nature 553: 91-95, 2018. Note: Erratum: Nature 571: E10, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29160310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29160310</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29160310[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/nature25015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29160310">Zhang et al. (2018)</a> showed that PDL1 (<a href="/entry/605402">605402</a>) protein abundance is regulated by cyclin D (<a href="/entry/168461">168461</a>)-CDK4 (<a href="/entry/123829">123829</a>) and the CUL3-SPOP (<a href="/entry/602650">602650</a>) E3 ligase via proteasome-mediated degradation. Inhibition of CDK4 and CDK6 (<a href="/entry/603368">603368</a>) in vivo increases PDL1 protein levels by impeding cyclin D-CDK4-mediated phosphorylation of SPOP and thereby promoting SPOP degradation by the anaphase-promoting complex activator FZR1 (<a href="/entry/603619">603619</a>). Loss-of-function mutations in SPOP compromise ubiquitination-mediated PDL1 degradation, leading to increased PDL1 levels and reduced numbers of tumor-infiltrating lymphocytes in mouse tumors and in primary human prostate cancer specimens. Notably, combining CDK4/6 inhibitor treatment with anti-PD1 (<a href="/entry/600244">600244</a>) immunotherapy enhances tumor regression and markedly improves overall survival rates in mouse tumor models. <a href="#24" class="mim-tip-reference" title="Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., Tan, Y., Ci, Y., Wu, F., Dai, X., Guo, J., Huang, Y.-H., Fan, C., Ren, S., Sun, Y., Freeman, G. J., Sicinski, P., Wei, W. <strong>Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance.</strong> Nature 553: 91-95, 2018. Note: Erratum: Nature 571: E10, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29160310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29160310</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29160310[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/nature25015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29160310">Zhang et al. (2018)</a> concluded that their study uncovered a novel molecular mechanism for regulating PDL1 protein stability by a cell cycle kinase and revealed the potential for using combination treatment with CDK4/6 inhibitors and PD1-PDL1 immune checkpoint blockade to enhance therapeutic efficacy for human cancers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29160310" 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="biochemicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#2" class="mim-tip-reference" title="Canning, P., Cooper, C. D. O., Krojer, T., Murray, J. W., Pike, A. C. W., Chaikuad, A., Keates, T., Thangaratnarajah, C., Hojzan, V., Ayinampudi, V., Marsden, B. D., Gileadi, O., Knapp, S., von Delft, F., Bullock, A. N. <strong>Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases.</strong> J. Biol. Chem. 288: 7803-7814, 2013. Note: Erratum: J. Biol. Chem. 288: 28304 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23349464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23349464</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23349464[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.M112.437996" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23349464">Canning et al. (2013)</a> determined the crystal structure of the BTB-BACK domains of human KLHL11 (<a href="/entry/619078">619078</a>) at 2.6-angstrom resolution. The BTB-BACK domains formed a homodimer with an elongated shape. KLHL11 had 8 alpha helices in total, with the 2 N-terminal helices forming the 3-box motif through which KLHL11 binds CUL3 to form E3 ubiquitin ligases. A 16-angstrom deep and 18-angstrom wide hydrophobic groove between the BTB and BACK domains exposed the 3-box for cullin interaction. The authors also determined the crystal structure of the BTB-BACK domains of KLHL11 in complex with the N-terminal cullin repeat domain of CUL3 at 2.8-angstrom resolution. The structure revealed interaction between the specific N-terminal extension sequence of CUL3 and the 3-box motif of KLHL11. In KLHL11-CUL3 assemblies, each subunit in the KLHL11 homodimer bound to 1 molecule of CUL3 and exhibited a 2-fold symmetry axis across the BTB dimer in a heterotetramer, further highlighting the importance of the N-terminal extension for CUL3 binding. Using other structures, the authors built the missing structural domains in the E3 ligase and proposed a working model of the complete dimeric BTB-Kelch class of E3 ligase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23349464" 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>Pseudohypoaldosteronism Type II</em></strong></p><p>
|
|
<a href="#1" class="mim-tip-reference" title="Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., and 34 others. <strong>Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.</strong> Nature 482: 98-102, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22266938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22266938</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22266938[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/nature10814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22266938">Boyden et al. (2012)</a> identified mutations in CUL3 segregating in de novo or autosomal dominant forms of pseudohypoaldosteronism type II (PHA2E; <a href="/entry/614496">614496</a>). Seventeen of 52 PHA2 kindreds had mutations in CUL3; all were heterozygous. Eight of the 17 were documented to be de novo, providing overwhelming evidence that these mutations are disease-causing. CUL3 mutations all clustered in sites implicated in splicing of exon 9, including the intron 8 splice acceptor (n = 4), the intron 9 splice donor (n = 5), the putative intron 8 splice branch site (n = 5), and a putative splice enhancer in exon 9 (n = 3, within a TTGGA(T/A)) splice enhancer consensus sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22266938" 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>Neurodevelopmental Disorder with or without Autism or Seizures</em></strong></p><p>
|
|
In a 3-year-old boy (family 2) with neurodevelopmental disorder with or without autism or seizures (NEDAUS; <a href="/entry/619239">619239</a>), <a href="#20" class="mim-tip-reference" title="Thiffault, I., Cadieux-Dion, M., Farrow, E., Caylor, R., Miller, N., Soden, S., Saunders, C. <strong>On the verge of diagnosis: detection, reporting, and investigation of de novo variants in novel genes identified by clinical sequencing.</strong> Hum. Mutat. 39: 1505-1516, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30311385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30311385</a>] [<a href="https://doi.org/10.1002/humu.23646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30311385">Thiffault et al. (2018)</a> identified a de novo heterozygous missense mutation in the CUL3 gene (Y58C; <a href="#0008">603136.0008</a>). The mutation, which was found by trio-based next-generation sequencing, was considered to be pathogenic after curation using a point-based system. Functional studies of the variant were not performed. The authors noted that several large studies had identified de novo mutations in the CUL3 gene in patients with variable neurodevelopmental disorders. For example, <a href="#12" class="mim-tip-reference" title="Kong, A., Frigge, M. L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., Gudjonsson, S. A., Sigurdsson, A., Jonasdottir, A., Jonasdottir, A., Wong, W. S. W., Sigurdsson, G., and 9 others. <strong>Rate of de novo mutations and the importance of father's age to disease risk.</strong> Nature 488: 471-475, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22914163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22914163</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22914163[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/nature11396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22914163">Kong et al. (2012)</a> identified a de novo heterozygous loss-of-function R546X variant in 1 of 44 Icelandic individuals with autism spectrum disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22914163+30311385" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 12-year-old Brazilian girl (F1389-1) with NEDAUS, <a href="#4" class="mim-tip-reference" title="da Silva Montenegro, E. M., Costa, C. S., Campos, G., Scliar, M., de Almeida, T. F., Zachi, E. C., Silva, I. M. W., Chan, A. J. S., Zarrei, M., Lourenco, N. C. V., Yamamoto, G. L., Scherer, S., Passos-Bueno, M. R. <strong>Meta-analyses support previous and novel autism candidate genes: outcomes of an unexplored Brazilian cohort.</strong> Autism Res. 13: 199-206, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31696658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31696658</a>] [<a href="https://doi.org/10.1002/aur.2238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31696658">da Silva Montenegro et al. (2020)</a> identified a de novo heterozygous nonsense mutation in the CUL3 gene (S133X; <a href="#0009">603136.0009</a>). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was classified as pathogenic according to ACMG criteria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31696658" 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 3 unrelated children with NEDAUS, <a href="#16" class="mim-tip-reference" title="Nakashima, M., Kato, M., Matsukura, M., Kira, R., Ngu, L.-H., Lichtenbelt, K. D., van Gassen, K. L. I., Mitsuhashi, S., Saitsu, H., Matsumoto, N. <strong>De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms.</strong> J. Hum. Genet. 65: 727-734, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32341456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32341456</a>] [<a href="https://doi.org/10.1038/s10038-020-0758-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32341456">Nakashima et al. (2020)</a> identified de novo heterozygous mutations in the CUL3 gene (<a href="#0010">603136.0010</a>-<a href="#0012">603136.0012</a>). There were 2 frameshift mutations and 1 missense mutation. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were not present in the dbSNP (build 153) or gnomAD databases. All were predicted or demonstrated to result in a loss of function and haploinsufficiency. Two patients were ascertained from a cohort of 1,230 individuals with childhood-onset epilepsy who underwent whole-exome sequencing; the third patient was identified through the GeneMatcher program. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32341456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 4-year-old Japanese girl with NEDAUS, <a href="#9" class="mim-tip-reference" title="Iwafuchi, S., Kikuchi, A., Endo, W., Inui, T., Aihara, Y., Satou, K., Kaname, T., Kure, S. <strong>A novel stop-gain CUL3 mutation in a Japanese patient with autism spectrum disorder.</strong> Brain Dev. 43: 303-307, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33097317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33097317</a>] [<a href="https://doi.org/10.1016/j.braindev.2020.09.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33097317">Iwafuchi et al. (2021)</a> identified a de novo heterozygous frameshift mutation in the CUL3 gene (<a href="#0013">603136.0013</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the gnomAD database. The mutation was predicted to lead to nonsense-mediated mRNA decay and haploinsufficiency. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33097317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#17" class="mim-tip-reference" title="Papizan, J. B., Vidal, A. H., Bezprozvannaya, S., Bassel-Duby, R., Olson, E. N. <strong>Cullin-3-RING ubiquitin ligase activity is required for striated muscle function in mice.</strong> J. Biol. Chem. 293: 8802-8811, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29653945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29653945</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29653945[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.RA118.002104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29653945">Papizan et al. (2018)</a> found that mice with skeletal muscle-specific deletion of Cul3 were born in normal mendelian ratios but became cyanotic shortly after birth and died due to inability to breathe. At embryonic day 18.5, mutant embryos displayed physical features characteristic of defective myogenesis or excitation-contraction coupling. Histologic analysis of tongue musculature revealed reduced muscle mass, disorganized sarcomeres, and multinucleated myofibers in mutant mice. Proteomic analysis showed that deletion of Cul3 affected extracellular matrix deposition and sarcomere maturation/function. The authors found that mice with cardiomyocyte-specific deletion of Cul3 were born in normal mendelian ratios and were morphologically indistinguishable from wildtype at birth. However, these mutant mice exhibited failure to thrive, were much smaller compared with wildtype by postnatal day 5 (P5), and died around P6 with severe cardiomyopathy. Histologic examination of heart muscles showed widespread cardiomyocyte vacuolization and protein aggregate deposition. Proteomic analysis revealed an altered metabolic profile, indicating that Cul3-dependent proteostasis is a critical regulator of cardiac antioxidative and metabolic processes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29653945" 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="Dong, Z., Chen, W., Chen, C., Wang, H., Cui, W., Tan, Z., Robinson, H., Gao, N., Luo, B., Zhang, L., Zhao, K., Xiong, W.-C., Mei, L. <strong>CUL3 deficiency causes social deficits and anxiety-like behaviors by impairing excitation-inhibition balance through the promotion of Cap-dependent translation.</strong> Neuron 105: 475-490, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31780330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31780330</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31780330[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.neuron.2019.10.035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31780330">Dong et al. (2020)</a> found that mice with homozygous deletion of Cul3 had reduced body size and brain weight compared with wildtype and died prematurely. Mice heterozygous for Cul3 deletion (Cul3-deficient mice) had more than 40% reduced level of Cul3, but they were viable and fertile, survived as long as wildtype, and did not show deficits observed in mice with homozygous Cul3 deletion. Cul3-deficient mice exhibited social behavioral deficits and anxiety-like behaviors. Hippocampus of Cul3-deficient mice had increased spine density, neuronal excitability, and synaptic transmission and disrupted excitation-inhibition (E-I) balance in CA1 neurons. Similar deficits were observed in pyramidal neurons with Cul3 deficiency, demonstrating a cell-autonomous role of Cul3 for synaptic function, E-I balance, and behavior. Proteomic analysis identified Eif4g1 (<a href="/entry/600495">600495</a>) as a target of Cul3-dependent ubiquitination. Consequently, Cul3 deficiency increased Eif4g1 level and upregulated Cap-dependent protein synthesis in brain. Inhibition of Cap-dependent translation diminished synaptic and social deficits in Cul3-deficient mice, but it had little effect on anxiety-like behaviors. However, chemogenetic inhibition of pyramidal neuron activity in hippocampus attenuated anxiety-like behavior in mutant mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31780330" 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>13 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/603136" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603136[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 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, IVS8, A-G, -26
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199469650 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199469650;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=rs199469650" 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=rs199469650" 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=RCV000023252 OR RCV000128488 OR RCV004700408" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023252, RCV000128488, RCV004700408" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023252...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 families, 3 with de novo occurrence of pseudohypoaldosteronism, type IIE (PHA2E; <a href="/entry/614496">614496</a>), <a href="#1" class="mim-tip-reference" title="Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., and 34 others. <strong>Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.</strong> Nature 482: 98-102, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22266938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22266938</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22266938[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/nature10814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22266938">Boyden et al. (2012)</a> identified an A-to-G transition at the -26 position of the intron 8 splice acceptor site in the CUL3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22266938" 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 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, IVS8, T-G, -28
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs199469649 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199469649;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs199469649?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs199469649" 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=rs199469649" 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=RCV000023253 OR RCV000128489" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023253, RCV000128489" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023253...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family segregating autosomal dominant pseudohypoaldosteronism type IIE (PHA2E; <a href="/entry/614496">614496</a>), <a href="#1" class="mim-tip-reference" title="Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., and 34 others. <strong>Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.</strong> Nature 482: 98-102, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22266938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22266938</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22266938[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/nature10814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22266938">Boyden et al. (2012)</a> identified an T-to-G transversion at the -28 position of the intron 8 splice branch point in the CUL3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22266938" 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 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, IVS8, T-G, -12
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199469651 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199469651;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=rs199469651" 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=rs199469651" 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=RCV000023254 OR RCV000128486" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023254, RCV000128486" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023254...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with pseudohypoaldosteronism type IIE (PHA2E; <a href="/entry/614496">614496</a>), <a href="#1" class="mim-tip-reference" title="Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., and 34 others. <strong>Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.</strong> Nature 482: 98-102, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22266938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22266938</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22266938[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/nature10814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22266938">Boyden et al. (2012)</a> identified an T-to-G transversion in the CUL3 gene, at the -12 position of the intron 8 splice acceptor site, within the polypyrimidine tract. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22266938" 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 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, IVS8, T-A, -5
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199469652 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199469652;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=rs199469652" 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=rs199469652" 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=RCV000023255 OR RCV000128491" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023255, RCV000128491" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023255...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a de novo case of pseudohypoaldosteronism type IIE (PHA2E; <a href="/entry/614496">614496</a>), <a href="#1" class="mim-tip-reference" title="Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., and 34 others. <strong>Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.</strong> Nature 482: 98-102, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22266938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22266938</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22266938[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/nature10814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22266938">Boyden et al. (2012)</a> identified an T-to-A transversion in the CUL3 gene, at the -5 position of the intron 8 splice acceptor site, within the polypyrimidine tract. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22266938" 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 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, IVS8, C-T, -3
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199469653 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199469653;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=rs199469653" 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=rs199469653" 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=RCV000023256 OR RCV000128490" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023256, RCV000128490" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023256...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a de novo case of pseudohypoaldosteronism type IIE (PHA2E; <a href="/entry/614496">614496</a>), <a href="#1" class="mim-tip-reference" title="Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., and 34 others. <strong>Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.</strong> Nature 482: 98-102, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22266938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22266938</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22266938[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/nature10814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22266938">Boyden et al. (2012)</a> identified a C-to-T transition at the -3 position of the intron 8 splice acceptor site of the CUL3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22266938" 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 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, IVS8, G-A, -1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199469654 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199469654;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=rs199469654" 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=rs199469654" 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=RCV000023257 OR RCV000128487" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023257, RCV000128487" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023257...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected members of a 2-generation family with pseudohypoaldosteronism type IIE (PHA2E; <a href="/entry/614496">614496</a>), <a href="#1" class="mim-tip-reference" title="Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., and 34 others. <strong>Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.</strong> Nature 482: 98-102, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22266938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22266938</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22266938[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/nature10814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22266938">Boyden et al. (2012)</a> identified a G-to-A transition in the CUL3 gene, at the -1 position of the intron 8 splice acceptor site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22266938" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, ASP413GLY
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199469656 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199469656;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=rs199469656" 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=rs199469656" 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=RCV000023258 OR RCV000128493" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023258, RCV000128493" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023258...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 families with undetermined pseudohypoaldosteronism type IIE (PHA2E; <a href="/entry/614496">614496</a>), <a href="#1" class="mim-tip-reference" title="Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., and 34 others. <strong>Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.</strong> Nature 482: 98-102, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22266938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22266938</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22266938[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/nature10814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22266938">Boyden et al. (2012)</a> identified an A-to-G transition resulting in an asp-to-gly substitution at codon 413 (D413G) within exon 9 of the CUL3 gene that resulted in an ES enhancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22266938" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM OR SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, TYR58CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1553535841 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553535841;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=rs1553535841" 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=rs1553535841" 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=RCV000677281 OR RCV000987041 OR RCV001352922" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000677281, RCV000987041, RCV001352922" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000677281...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-year-old boy (family 2) with neurodevelopmental disorder without seizures or autism (NEDAUS; <a href="/entry/619239">619239</a>), <a href="#20" class="mim-tip-reference" title="Thiffault, I., Cadieux-Dion, M., Farrow, E., Caylor, R., Miller, N., Soden, S., Saunders, C. <strong>On the verge of diagnosis: detection, reporting, and investigation of de novo variants in novel genes identified by clinical sequencing.</strong> Hum. Mutat. 39: 1505-1516, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30311385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30311385</a>] [<a href="https://doi.org/10.1002/humu.23646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30311385">Thiffault et al. (2018)</a> identified a de novo heterozygous c.173A-G transition in the CUL3 gene, resulting in a tyr58-to-cys (Y58C) substitution. The mutation, which was found by trio-based next-generation sequencing, was considered to be pathogenic after curation using a point-based system. Functional studies of the variant were not performed. The child had failure to thrive, microcephaly, speech delay, and absent thumb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30311385" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 NEURODEVELOPMENTAL DISORDER WITH AUTISM WITHOUT SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, SER133TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs981700726 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs981700726;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=rs981700726" 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=rs981700726" 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=RCV001352923" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001352923" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001352923</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 12-year-old Brazilian girl (F1389-1) with neurodevelopmental disorder with autism but without seizures (NEDAUS; <a href="/entry/619239">619239</a>), <a href="#4" class="mim-tip-reference" title="da Silva Montenegro, E. M., Costa, C. S., Campos, G., Scliar, M., de Almeida, T. F., Zachi, E. C., Silva, I. M. W., Chan, A. J. S., Zarrei, M., Lourenco, N. C. V., Yamamoto, G. L., Scherer, S., Passos-Bueno, M. R. <strong>Meta-analyses support previous and novel autism candidate genes: outcomes of an unexplored Brazilian cohort.</strong> Autism Res. 13: 199-206, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31696658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31696658</a>] [<a href="https://doi.org/10.1002/aur.2238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31696658">da Silva Montenegro et al. (2020)</a> identified a de novo heterozygous c.398C-G transversion (c.398C-G, NM_001257197) in exon 4 of the CUL3 gene, resulting in a ser133-to-ter (S133X) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was classified as pathogenic according to ACMG criteria. The patient had autism spectrum disorder, with mild motor and speech delay. She did not have seizures. Functional studies of the variant were not performed, but it was predicted to result in a loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31696658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM WITH SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, VAL285ALA
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1343840421 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1343840421;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1343840421?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1343840421" 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=rs1343840421" 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=RCV001352924" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001352924" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001352924</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-year-old Japanese girl (patient 1) with neurodevelopmental disorder without autism but with seizures (NEDAUS; <a href="/entry/619239">619239</a>), <a href="#16" class="mim-tip-reference" title="Nakashima, M., Kato, M., Matsukura, M., Kira, R., Ngu, L.-H., Lichtenbelt, K. D., van Gassen, K. L. I., Mitsuhashi, S., Saitsu, H., Matsumoto, N. <strong>De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms.</strong> J. Hum. Genet. 65: 727-734, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32341456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32341456</a>] [<a href="https://doi.org/10.1038/s10038-020-0758-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32341456">Nakashima et al. (2020)</a> identified a de novo heterozygous c.854T-C transition (c.854T-C, NM_003590.4) in the CUL3 gene, resulting in a val285-to-ala (V285A) substitution in the CR3 domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 153) or gnomAD databases. In vitro functional expression studies showed that the mutant protein had significantly weaker interaction with KEAP1 (<a href="/entry/606016">606016</a>) compared to wildtype, suggesting that it caused instability of the CRL complex. The patient had onset of intractable spasms and tonic seizures at 2 months of age. EEG showed a suppression-burst pattern, consistent with West syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32341456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM WITH SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, 1-BP DEL, 137G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1694759979 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1694759979;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=rs1694759979" 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=rs1694759979" 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=RCV001352925" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001352925" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001352925</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-year-old Malaysian boy (patient 2) with neurodevelopmental disorder without autism but with seizures (NEDAUS; <a href="/entry/619239">619239</a>), <a href="#16" class="mim-tip-reference" title="Nakashima, M., Kato, M., Matsukura, M., Kira, R., Ngu, L.-H., Lichtenbelt, K. D., van Gassen, K. L. I., Mitsuhashi, S., Saitsu, H., Matsumoto, N. <strong>De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms.</strong> J. Hum. Genet. 65: 727-734, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32341456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32341456</a>] [<a href="https://doi.org/10.1038/s10038-020-0758-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32341456">Nakashima et al. (2020)</a> identified a de novo heterozygous 1-bp deletion (c.137delG, NM_003590.4), resulting in a frameshift and premature termination (Arg46LeufsTer32). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 153) or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to result in a loss of function and haploinsufficiency. The patient had onset of intractable seizures at 6 months of age; EEG showed hypsarrhythmia, consistent with West syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32341456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM OR SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, 1-BP DEL, NT1239
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1692487571 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1692487571;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=rs1692487571" 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=rs1692487571" 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=RCV001352926" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001352926" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001352926</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old Dutch girl (patient 3) with neurodevelopmental disorder without autism or seizures (NEDAUS; <a href="/entry/619239">619239</a>), <a href="#16" class="mim-tip-reference" title="Nakashima, M., Kato, M., Matsukura, M., Kira, R., Ngu, L.-H., Lichtenbelt, K. D., van Gassen, K. L. I., Mitsuhashi, S., Saitsu, H., Matsumoto, N. <strong>De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms.</strong> J. Hum. Genet. 65: 727-734, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32341456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32341456</a>] [<a href="https://doi.org/10.1038/s10038-020-0758-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32341456">Nakashima et al. (2020)</a> identified a de novo heterozygous 1-bp deletion (c.1239del, NM_003590.4) in the CUL3 gene, resulting in a frameshift and premature termination (Asp413GlufsTer42). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 153) or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to result in a loss of function and haploinsufficiency. The patient had mild intellectual disability with poor speech. She did not have seizures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32341456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 NEURODEVELOPMENTAL DISORDER WITH AUTISM AND SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CUL3, 2-BP INS, 1758TG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1692153577 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1692153577;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=rs1692153577" 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=rs1692153577" 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=RCV001352927" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001352927" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001352927</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old Japanese girl with neurodevelopmental disorder with autism and seizures (NEDAUS; <a href="/entry/619239">619239</a>), <a href="#9" class="mim-tip-reference" title="Iwafuchi, S., Kikuchi, A., Endo, W., Inui, T., Aihara, Y., Satou, K., Kaname, T., Kure, S. <strong>A novel stop-gain CUL3 mutation in a Japanese patient with autism spectrum disorder.</strong> Brain Dev. 43: 303-307, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33097317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33097317</a>] [<a href="https://doi.org/10.1016/j.braindev.2020.09.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33097317">Iwafuchi et al. (2021)</a> identified a de novo heterozygous 2-bp insertion (c.1758_1759insTG, NM_003590.5) in exon 13 of the CUL3 gene, resulting in a frameshift and premature termination (Thr587Ter). The mutation, which was found whole-exome sequencing and confirmed by Sanger sequencing, was not present in the gnomAD database. The mutation was predicted to lead to nonsense-mediated mRNA decay and haploinsufficiency. Functional studies of the variant were not performed. The patient presented at age 21 months with status epilepticus and thereafter showed developmental regression with loss of eye contact, autistic features, and features of Rett syndrome (RTT; <a href="/entry/312750">312750</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33097317" 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="Boyden2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., and 34 others.
|
|
<strong>Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.</strong>
|
|
Nature 482: 98-102, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22266938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22266938</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22266938[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=22266938" 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/nature10814" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Canning2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Canning, P., Cooper, C. D. O., Krojer, T., Murray, J. W., Pike, A. C. W., Chaikuad, A., Keates, T., Thangaratnarajah, C., Hojzan, V., Ayinampudi, V., Marsden, B. D., Gileadi, O., Knapp, S., von Delft, F., Bullock, A. N.
|
|
<strong>Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases.</strong>
|
|
J. Biol. Chem. 288: 7803-7814, 2013. Note: Erratum: J. Biol. Chem. 288: 28304 only, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23349464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23349464</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23349464[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=23349464" 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.M112.437996" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Cummings2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cummings, C. M., Bentley, C. A., Perdue, S. A., Baas, P. W., Singer, J. D.
|
|
<strong>The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal mitosis in mammalian cells.</strong>
|
|
J. Biol. Chem. 284: 11663-11675, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19261606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19261606</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19261606[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=19261606" 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.M809374200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="da Silva Montenegro2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
da Silva Montenegro, E. M., Costa, C. S., Campos, G., Scliar, M., de Almeida, T. F., Zachi, E. C., Silva, I. M. W., Chan, A. J. S., Zarrei, M., Lourenco, N. C. V., Yamamoto, G. L., Scherer, S., Passos-Bueno, M. R.
|
|
<strong>Meta-analyses support previous and novel autism candidate genes: outcomes of an unexplored Brazilian cohort.</strong>
|
|
Autism Res. 13: 199-206, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31696658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31696658</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31696658" 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/aur.2238" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Dong2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dong, Z., Chen, W., Chen, C., Wang, H., Cui, W., Tan, Z., Robinson, H., Gao, N., Luo, B., Zhang, L., Zhao, K., Xiong, W.-C., Mei, L.
|
|
<strong>CUL3 deficiency causes social deficits and anxiety-like behaviors by impairing excitation-inhibition balance through the promotion of Cap-dependent translation.</strong>
|
|
Neuron 105: 475-490, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31780330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31780330</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31780330[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=31780330" 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.neuron.2019.10.035" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Du1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Du, M., Sansores-Garcia, L., Zu, Z., Wu, K. K.
|
|
<strong>Cloning and expression analysis of a novel salicylate suppressible gene, Hs-CUL-3, a member of cullin/Cdc53 family.</strong>
|
|
J. Biol. Chem. 273: 24289-24292, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9733711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9733711</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9733711" 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.273.38.24289" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Hartz2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hartz, P. A.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 3/14/2012.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Ishikawa1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ishikawa, K., Nagase, T., Suyama, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
|
|
<strong>Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong>
|
|
DNA Res. 5: 169-176, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9734811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9734811</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9734811" 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/5.3.169" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Iwafuchi2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iwafuchi, S., Kikuchi, A., Endo, W., Inui, T., Aihara, Y., Satou, K., Kaname, T., Kure, S.
|
|
<strong>A novel stop-gain CUL3 mutation in a Japanese patient with autism spectrum disorder.</strong>
|
|
Brain Dev. 43: 303-307, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33097317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33097317</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33097317" 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.braindev.2020.09.015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Jin2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jin, L., Pahuja, K. B., Wickliffe, K. E., Gorur, A., Baumgartel, C., Schekman, R., Rape, M.
|
|
<strong>Ubiquitin-dependent regulation of COPII coat size and function.</strong>
|
|
Nature 482: 495-500, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22358839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22358839</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22358839[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=22358839" 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/nature10822" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Kipreos1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kipreos, E. T., Lander, L. E., Wing, J. P., He, W. W., Hedgecock, E. M.
|
|
<strong>cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family.</strong>
|
|
Cell 85: 829-839, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8681378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8681378</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8681378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(00)81267-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Kong2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kong, A., Frigge, M. L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., Gudjonsson, S. A., Sigurdsson, A., Jonasdottir, A., Jonasdottir, A., Wong, W. S. W., Sigurdsson, G., and 9 others.
|
|
<strong>Rate of de novo mutations and the importance of father's age to disease risk.</strong>
|
|
Nature 488: 471-475, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22914163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22914163</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22914163[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=22914163" 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/nature11396" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Maerki2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maerki, S., Olma, M. H., Staubli, T., Steigemann, P., Gerlich, D. W., Quadroni, M., Sumara, I., Peter, M.
|
|
<strong>The Cul3-KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis.</strong>
|
|
J. Cell Biol. 187: 791-800, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19995937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19995937</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19995937[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=19995937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1083/jcb.200906117" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Mathew2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mathew, R., Seiler, M. P., Scanlon, S. T., Mao, A., Constantinides, M. G., Bertozzi-Villa, C., Singer, J. D., Bendelac, A.
|
|
<strong>BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs.</strong>
|
|
Nature 491: 618-621, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23086144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23086144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23086144[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=23086144" 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/nature11548" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Michel1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Michel, J. J., Xiong, Y.
|
|
<strong>Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A.</strong>
|
|
Cell Growth Differ. 9: 435-449, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9663463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9663463</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9663463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Nakashima2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nakashima, M., Kato, M., Matsukura, M., Kira, R., Ngu, L.-H., Lichtenbelt, K. D., van Gassen, K. L. I., Mitsuhashi, S., Saitsu, H., Matsumoto, N.
|
|
<strong>De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms.</strong>
|
|
J. Hum. Genet. 65: 727-734, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32341456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32341456</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32341456" 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/s10038-020-0758-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Papizan2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Papizan, J. B., Vidal, A. H., Bezprozvannaya, S., Bassel-Duby, R., Olson, E. N.
|
|
<strong>Cullin-3-RING ubiquitin ligase activity is required for striated muscle function in mice.</strong>
|
|
J. Biol. Chem. 293: 8802-8811, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29653945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29653945</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29653945[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=29653945" 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.RA118.002104" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Rondou2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rondou, P., Haegeman, G., Vanhoenacker, P., Van Craenenbroeck, K.
|
|
<strong>BTB protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase.</strong>
|
|
J. Biol. Chem. 283: 11083-11096, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18303015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18303015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18303015[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=18303015" 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.M708473200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Sumara2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sumara, I., Quadroni, M., Frei, C., Olma, M. H., Sumara, G., Ricci, R., Peter, M.
|
|
<strong>A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells.</strong>
|
|
Dev. Cell 12: 887-900, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17543862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17543862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17543862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.devcel.2007.03.019" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Thiffault2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thiffault, I., Cadieux-Dion, M., Farrow, E., Caylor, R., Miller, N., Soden, S., Saunders, C.
|
|
<strong>On the verge of diagnosis: detection, reporting, and investigation of de novo variants in novel genes identified by clinical sequencing.</strong>
|
|
Hum. Mutat. 39: 1505-1516, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30311385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30311385</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30311385" 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/humu.23646" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Tian2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tian, M., Hao, F., Jin, X., Sun, X., Jiang, Y., Wang, Y., Li, D., Chang, T., Zou, Y., Peng, P., Xia, C., Liu, J., Li, Y., Wang, P., Feng, Y., Wei, M.
|
|
<strong>ACLY ubiquitination by CUL3-KLHL25 induces the reprogramming of fatty acid metabolism to facilitate iTreg differentiation.</strong>
|
|
eLife 10: e62394, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34491895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34491895</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34491895[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=34491895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7554/eLife.62394" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Werner2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Werner, A., Iwasaki, S., McGourty, C. A., Medina-Ruiz, S., Teerikorpi, N., Fedrigo, I., Ingolia, N. T., Rape, M.
|
|
<strong>Cell-fate determination by ubiquitin-dependent regulation of translation.</strong>
|
|
Nature 525: 523-527, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26399832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26399832</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26399832[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=26399832" 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/nature14978" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Zhang2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, C., Liu, J., Huang, G., Zhao, Y., Yue, X., Wu, H., Li, J., Zhu, J., Shen, Z., Haffty, B. G., Hu, W., Feng, Z.
|
|
<strong>Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression.</strong>
|
|
Genes Dev. 30: 1956-1970, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27664236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27664236</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27664236[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=27664236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.283283.116" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Zhang2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., Tan, Y., Ci, Y., Wu, F., Dai, X., Guo, J., Huang, Y.-H., Fan, C., Ren, S., Sun, Y., Freeman, G. J., Sicinski, P., Wei, W.
|
|
<strong>Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance.</strong>
|
|
Nature 553: 91-95, 2018. Note: Erratum: Nature 571: E10, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29160310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29160310</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29160310[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=29160310" 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/nature25015" 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">
|
|
Bao Lige - updated : 05/25/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 03/18/2021<br>Bao Lige - updated : 11/02/2020<br>Bao Lige - updated : 06/22/2020<br>Bao Lige - updated : 05/13/2020<br>Bao Lige - updated : 07/11/2019<br>Ada Hamosh - updated : 04/12/2018<br>Patricia A. Hartz - updated : 10/21/2015<br>Patricia A. Hartz - updated : 3/10/2015<br>Ada Hamosh - updated : 12/13/2012<br>Patricia A. Hartz - updated : 3/14/2012<br>Patricia A. Hartz - updated : 3/8/2012<br>Ada Hamosh - updated : 2/22/2012<br>Patricia A. Hartz - updated : 6/26/2007
|
|
</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">
|
|
Rebekah S. Rasooly : 10/13/1998
|
|
</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">
|
|
mgross : 05/25/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 04/14/2021<br>carol : 03/25/2021<br>alopez : 03/24/2021<br>ckniffin : 03/18/2021<br>mgross : 11/02/2020<br>mgross : 06/22/2020<br>mgross : 06/04/2020<br>mgross : 05/13/2020<br>carol : 10/03/2019<br>mgross : 07/11/2019<br>mgross : 06/21/2018<br>mgross : 06/21/2018<br>alopez : 04/12/2018<br>carol : 02/09/2018<br>mgross : 10/21/2015<br>mgross : 3/11/2015<br>mcolton : 3/10/2015<br>alopez : 12/21/2012<br>terry : 12/13/2012<br>mgross : 5/23/2012<br>terry : 3/14/2012<br>mgross : 3/8/2012<br>terry : 3/8/2012<br>alopez : 2/27/2012<br>terry : 2/22/2012<br>mgross : 7/12/2007<br>terry : 6/26/2007<br>alopez : 10/30/1998<br>dkim : 10/28/1998<br>alopez : 10/13/1998
|
|
</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> 603136
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CULLIN 3; CUL3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: CUL3</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 2q36.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 2:224,470,150-224,585,363 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
2q36.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Neurodevelopmental disorder with or without autism or seizures
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
619239
|
|
</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">
|
|
Pseudohypoaldosteronism, type IIE
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614496
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The CUL3 gene encodes a scaffolding component of the Cullin-RING ligase (CRL) complex, which belongs to a class of E3 ubiquitin ligases that mediate polyubiquitination of specific target proteins destined for degradation (summary by Nakashima et al., 2020). </p><p>CUL3 is a component of a ubiquitin E3 ligase that is essential for mitotic division (Sumara et al., 2007). </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>Kipreos et al. (1996) identified a conserved gene family, designated cullins (see CUL1, 603134), with at least 5 members in nematodes, 6 in humans, and 3 in S. cerevisiae. Human CUL3 is an ortholog of nematode cul3. Michel and Xiong (1998) identified human CUL3 cDNAs and reported that the predicted protein is 768 amino acids long. </p><p>By sequencing clones isolated from a size-fractionated human brain cDNA library, Ishikawa et al. (1998) isolated CUL3, which they designated KIAA0617. The deduced protein contains 768 amino acids. RT-PCR analysis detected highest CUL3 expression in ovary, followed by skeletal muscle and brain. Weaker expression was detected in heart, lung, liver, kidney, and testis, with little to no expression in other tissues examined. </p><p>Du et al. (1998) identified CUL3 as a gene whose expression in human fibroblasts was induced by phorbol 12-myristate 13-acetate (PMA) and suppressed by salicylate. They reported that the sequences of the human and C. elegans cul3 proteins share 46% identity. Northern blot analysis revealed that CUL3 is expressed as major 2.8- and minor 4.3-kb transcripts in various human tissues, with the highest levels in skeletal muscle and heart. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By analysis of a radiation hybrid panel, Ishikawa et al. (1998) mapped the CUL3 gene to human chromosome 2. </p><p>Hartz (2012) mapped the CUL3 gene to chromosome 2q36.2 based on an alignment of the CUL3 sequence (GenBank AF062537) with the genomic sequence (GRCh37).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Sumara et al. (2007) found that KLHL9 (611201), KLHL13 (300655), and CUL3 interacted directly in a 370-kD protein complex in HeLa cell lysates. The CUL3/KLHL9/KLHL13 complex was the minimum unit required for correct chromosome alignment in metaphase, proper midzone and midbody formation, and completion of cytokinesis. CUL3/KLHL9/KLHL13 acted as an E3 ligase and regulated dynamic localization of the chromosomal passenger complex (CPC) protein Aurora B (AURKB; 604970) on mitotic chromosomes and accumulation of Aurora B on the central spindle after anaphase onset. Aurora B directly bound the substrate-recognition domains of KLHL9 and KLHL13 in vitro and coimmunoprecipitated with the CUL3/KLHL9/KLHL13 complex during mitosis. Moreover, Aurora B was ubiquitylated in a CUL3-dependent manner in vivo and by reconstituted CUL3/KLHL9/KLHL13 in vitro. Sumara et al. (2007) concluded that CUL3/KLHL9/KLHL13 is an E3 ligase that controls the dynamic behavior of Aurora B on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. </p><p>Using mass spectrometric analysis, Maerki et al. (2009) found that KLHL21 (616262) and KLHL22 (618020) immunoprecipitated with CUL3, KLHL9, and KLHL13 from HeLa cell lysates. KLHL21 also interacted with Aurora B. Deletion analysis revealed that the BTB domain of KLHL21 was required for interaction with CUL3. Time-lapse microscopy revealed that knockdown of KLHL21 or KLHL22 via small interfering RNA delayed prometaphase and led to failure of proper metaphase plate formation. Knockdown of KLHL21, but not KLHL22, also caused multinucleation and failure of cytokinesis in a large number of cells. During anaphase, loss of KLHL21 inhibited translocation of Aurora B from segregating chromosomes to the spindle midzone and caused loss of CUL3 localization at the midzone. Likewise, knockdown of CUL3 caused loss of KLHL21 from the midzone. Sucrose gradient and gel filtration experiments revealed that KLHL21 and KLHL9 fractionated into overlapping but distinct CUL3 complexes, suggesting that KLHL21, KLHL9, and KLHL13 assemble distinct CUL3 complexes to regulate CPC localization during mitosis. CUL3-KLHL21 complexes also ubiquitinated Aurora B in vitro. Maerki et al. (2009) concluded that different CUL3 complexes with KLHL9, KLHL13, and KLHL21 may target different pools of Aurora B for mitotic progression. </p><p>Rondou et al. (2008) showed that interaction between KLHL12 (614522) and the CUL3 ubiquitin ligase complex directed ubiquitination of dopamine receptor D4 (DRD4; 126452). KLHL12 interacted directly with CUL3 and with the polymorphic intracellular loop-3 of D4. Knockdown of KLHL12 in KLHL12-overexpressing HEK293 cells abolished association of D4 with CUL3, and knockdown of CUL3 decreased ubiquitination of D4. </p><p>Using yeast 2-hybrid and immunoprecipitation analyses, Cummings et al. (2009) showed that human KLHDC5 (KLHL42; 618919) and CUL3 physically interacted through the BTB domain of KLHDC5. Overexpression of KLHDC5 in HeLa cells stabilized microtubules and inhibited microtubule depolymerization required for normal cell morphology and mitosis, resulting in cells with multiple nuclei. In contrast, knockdown of KLHDC5 caused a dramatic loss of microtubule structure. Like KLHDC5, the microtubule-severing protein p60 (KATNA1; 606696) was also expressed in mitotic cells, and its levels in were regulated by KLHDC5. p60 interacted with both CUL3 and KLHDC5, and at least 1 of the 3 kelch domains of KLHDC5 was required for the interaction. KLHDC5 served as a substrate recognition adaptor to recruit p60 to the CUL3-KLHDC5 complex, and CUL3 facilitated ubiquitination of p60 to mediate its degradation. CUL3 regulation of p60 abundance was vital for faithful progression of mitosis, as knockdown of CUL3 in HeLa cells increased p60 levels and resulted in accumulation of multinucleated cells due to their inability to complete cytokinesis. </p><p>Jin et al. (2012) found that depletion of either Klhl12 or Cul3 in mouse embryonic stem cells resulted in cell compaction and delayed proliferation. Depletion of Cul3 in mouse fibroblasts had a much weaker effect. Overexpression and depletion studies showed that interaction of Klhl12 with Cul3 was required for monoubiquitination of the coat protein complex II (COPII) component Sec31 (see 610257). Overexpression of Klhl12 resulted in expansion of the diameter of Sec31-containing COPII vesicles, and this expansion was required for transport and secretion of large cargo proteins, such as procollagens (see 120150). A Sec31-binding mutant of Klhl12 neither colocalized with Sec31 nor induced formation of large vesicles. Disruption of KLHL12-CUL3 function in human HT1080 fibrosarcoma cells impaired COPII vesicle expansion and collagen export, but it had no effect on export of smaller cargo by small COPII vesicles. Jin et al. (2012) concluded that KLHL12-CUL3 monoubiquitination of SEC31 is required for COPII vesicle expansion to accommodate large or bulky cargo molecules. </p><p>Mathew et al. (2012) reported that PLZF is prominently associated with CUL3 in natural killer T cell thymocytes. PLZF transports CUL3 to the nucleus, where the 2 proteins are associated within a chromatin modifying complex. Furthermore, PLZF expression results in selective ubiquitination changes of several components of this complex. CUL3 was also found associated with the BTB-ZF transcription factor BCL6 (109565), which directs the germinal center B cell and follicular T-helper cell programs. Conditional CUL3 deletion in mice demonstrated an essential role for CUL3 in the development of PLZF- and BCL6-dependent lineages. Mathew et al. (2012) concluded that distinct lineage-specific BTB-ZF transcription factors recruit CUL3 to alter the ubiquitination pattern of their associated chromatin-modifying complex. They proposed that this function is essential to direct the differentiation of several T- and B-cell effector programs, and may also be involved in the oncogenic role of PLZF and BCL6 in leukemias and lymphomas. </p><p>KBTBD8 (616607) functions as an adaptor for substrate recognition by CUL3. Using mass spectrometric analysis, Werner et al. (2015) found that KBTBD8 interacted with TCOF1 (606847) and NOLC1 (602394). CUL3-KBTBD8 monoubiquitinated TCOF1 and NOLC1 in a manner that required the cofactor beta-arrestin (see 107940). Knockdown of KBTBD8, TCOF1, or NOLC1 in human embryonic stem cells (hESCs) via short hairpin RNA inhibited hESC differentiation into neural crest cells and accelerated hESC differentiation into central nervous system (CNS) precursors. Affinity purification revealed that ubiquitinated TCOF1-NOLC1 complexes engaged RNA polymerase I into complexes with the small ribosomal processing complex. Werner et al. (2015) hypothesized that KBTBD8-dependent ubiquitination drives formation of a TCOF1-NOLC1 platform in hESCs that connects RNA polymerase I with ribosome modification enzymes at specific mRNAs to delay accumulation of CNS precursor proteins until neural crest specification has occurred. </p><p>By coimmunoprecipitation and mass spectrometric analyses, Zhang et al. (2016) showed that ACLY (108728) interacted indirectly with CUL3 through KLHL25 (619893) to form a complex in human lung cancer H1299 cells. KLHL25 interacted directly with ACLY and functioned as a substrate adaptor to bridge ACLY to CUL3. CUL3-KLHL25 negatively regulated ACLY protein levels in cells through protein ubiquitination and degradation, and low CUL3 expression was associated with high ACLY expression in human lung cancer. Through negative regulation of ACLY, CUL3-KLHL25 reduced acetyl-CoA levels and inhibited lipid synthesis, which in turn contributed to the inhibitory effect of CUL3-KLHL25 on proliferation and anchorage-independent growth of lung cancer cells. In vivo analysis revealed that CUL3-KLHL25 inhibited growth of xenograft lung tumors in mice through negative regulation of ACLY. </p><p>Tian et al. (2021) found that Acly regulated differentiation of mouse inducible regulatory T cells (iTregs). Tgfb1 (190180) induced Acly downregulation through Cul3-Klhl25-mediated ubiquitination and degradation, which in turn facilitated iTreg differentiation. Analysis with human iTregs confirmed the conserved role of CUL3-KLHL25-mediated ACLY ubiquitination in iTreg differentiation. Analysis with a mouse inflammatory bowel disease (IBD; see 266600) model revealed an important role of Cul3-Klhl25-mediated Acly ubiquitination in colitis alleviation and in regulation of diarrhea. </p><p>Zhang et al. (2018) showed that PDL1 (605402) protein abundance is regulated by cyclin D (168461)-CDK4 (123829) and the CUL3-SPOP (602650) E3 ligase via proteasome-mediated degradation. Inhibition of CDK4 and CDK6 (603368) in vivo increases PDL1 protein levels by impeding cyclin D-CDK4-mediated phosphorylation of SPOP and thereby promoting SPOP degradation by the anaphase-promoting complex activator FZR1 (603619). Loss-of-function mutations in SPOP compromise ubiquitination-mediated PDL1 degradation, leading to increased PDL1 levels and reduced numbers of tumor-infiltrating lymphocytes in mouse tumors and in primary human prostate cancer specimens. Notably, combining CDK4/6 inhibitor treatment with anti-PD1 (600244) immunotherapy enhances tumor regression and markedly improves overall survival rates in mouse tumor models. Zhang et al. (2018) concluded that their study uncovered a novel molecular mechanism for regulating PDL1 protein stability by a cell cycle kinase and revealed the potential for using combination treatment with CDK4/6 inhibitors and PD1-PDL1 immune checkpoint blockade to enhance therapeutic efficacy for human cancers. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Canning et al. (2013) determined the crystal structure of the BTB-BACK domains of human KLHL11 (619078) at 2.6-angstrom resolution. The BTB-BACK domains formed a homodimer with an elongated shape. KLHL11 had 8 alpha helices in total, with the 2 N-terminal helices forming the 3-box motif through which KLHL11 binds CUL3 to form E3 ubiquitin ligases. A 16-angstrom deep and 18-angstrom wide hydrophobic groove between the BTB and BACK domains exposed the 3-box for cullin interaction. The authors also determined the crystal structure of the BTB-BACK domains of KLHL11 in complex with the N-terminal cullin repeat domain of CUL3 at 2.8-angstrom resolution. The structure revealed interaction between the specific N-terminal extension sequence of CUL3 and the 3-box motif of KLHL11. In KLHL11-CUL3 assemblies, each subunit in the KLHL11 homodimer bound to 1 molecule of CUL3 and exhibited a 2-fold symmetry axis across the BTB dimer in a heterotetramer, further highlighting the importance of the N-terminal extension for CUL3 binding. Using other structures, the authors built the missing structural domains in the E3 ligase and proposed a working model of the complete dimeric BTB-Kelch class of E3 ligase. </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>Pseudohypoaldosteronism Type II</em></strong></p><p>
|
|
Boyden et al. (2012) identified mutations in CUL3 segregating in de novo or autosomal dominant forms of pseudohypoaldosteronism type II (PHA2E; 614496). Seventeen of 52 PHA2 kindreds had mutations in CUL3; all were heterozygous. Eight of the 17 were documented to be de novo, providing overwhelming evidence that these mutations are disease-causing. CUL3 mutations all clustered in sites implicated in splicing of exon 9, including the intron 8 splice acceptor (n = 4), the intron 9 splice donor (n = 5), the putative intron 8 splice branch site (n = 5), and a putative splice enhancer in exon 9 (n = 3, within a TTGGA(T/A)) splice enhancer consensus sequence. </p><p><strong><em>Neurodevelopmental Disorder with or without Autism or Seizures</em></strong></p><p>
|
|
In a 3-year-old boy (family 2) with neurodevelopmental disorder with or without autism or seizures (NEDAUS; 619239), Thiffault et al. (2018) identified a de novo heterozygous missense mutation in the CUL3 gene (Y58C; 603136.0008). The mutation, which was found by trio-based next-generation sequencing, was considered to be pathogenic after curation using a point-based system. Functional studies of the variant were not performed. The authors noted that several large studies had identified de novo mutations in the CUL3 gene in patients with variable neurodevelopmental disorders. For example, Kong et al. (2012) identified a de novo heterozygous loss-of-function R546X variant in 1 of 44 Icelandic individuals with autism spectrum disorder. </p><p>In a 12-year-old Brazilian girl (F1389-1) with NEDAUS, da Silva Montenegro et al. (2020) identified a de novo heterozygous nonsense mutation in the CUL3 gene (S133X; 603136.0009). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was classified as pathogenic according to ACMG criteria. </p><p>In 3 unrelated children with NEDAUS, Nakashima et al. (2020) identified de novo heterozygous mutations in the CUL3 gene (603136.0010-603136.0012). There were 2 frameshift mutations and 1 missense mutation. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were not present in the dbSNP (build 153) or gnomAD databases. All were predicted or demonstrated to result in a loss of function and haploinsufficiency. Two patients were ascertained from a cohort of 1,230 individuals with childhood-onset epilepsy who underwent whole-exome sequencing; the third patient was identified through the GeneMatcher program. </p><p>In a 4-year-old Japanese girl with NEDAUS, Iwafuchi et al. (2021) identified a de novo heterozygous frameshift mutation in the CUL3 gene (603136.0013). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the gnomAD database. The mutation was predicted to lead to nonsense-mediated mRNA decay and haploinsufficiency. Functional studies of the variant were not performed. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Papizan et al. (2018) found that mice with skeletal muscle-specific deletion of Cul3 were born in normal mendelian ratios but became cyanotic shortly after birth and died due to inability to breathe. At embryonic day 18.5, mutant embryos displayed physical features characteristic of defective myogenesis or excitation-contraction coupling. Histologic analysis of tongue musculature revealed reduced muscle mass, disorganized sarcomeres, and multinucleated myofibers in mutant mice. Proteomic analysis showed that deletion of Cul3 affected extracellular matrix deposition and sarcomere maturation/function. The authors found that mice with cardiomyocyte-specific deletion of Cul3 were born in normal mendelian ratios and were morphologically indistinguishable from wildtype at birth. However, these mutant mice exhibited failure to thrive, were much smaller compared with wildtype by postnatal day 5 (P5), and died around P6 with severe cardiomyopathy. Histologic examination of heart muscles showed widespread cardiomyocyte vacuolization and protein aggregate deposition. Proteomic analysis revealed an altered metabolic profile, indicating that Cul3-dependent proteostasis is a critical regulator of cardiac antioxidative and metabolic processes. </p><p>Dong et al. (2020) found that mice with homozygous deletion of Cul3 had reduced body size and brain weight compared with wildtype and died prematurely. Mice heterozygous for Cul3 deletion (Cul3-deficient mice) had more than 40% reduced level of Cul3, but they were viable and fertile, survived as long as wildtype, and did not show deficits observed in mice with homozygous Cul3 deletion. Cul3-deficient mice exhibited social behavioral deficits and anxiety-like behaviors. Hippocampus of Cul3-deficient mice had increased spine density, neuronal excitability, and synaptic transmission and disrupted excitation-inhibition (E-I) balance in CA1 neurons. Similar deficits were observed in pyramidal neurons with Cul3 deficiency, demonstrating a cell-autonomous role of Cul3 for synaptic function, E-I balance, and behavior. Proteomic analysis identified Eif4g1 (600495) as a target of Cul3-dependent ubiquitination. Consequently, Cul3 deficiency increased Eif4g1 level and upregulated Cap-dependent protein synthesis in brain. Inhibition of Cap-dependent translation diminished synaptic and social deficits in Cul3-deficient mice, but it had little effect on anxiety-like behaviors. However, chemogenetic inhibition of pyramidal neuron activity in hippocampus attenuated anxiety-like behavior in mutant mice. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>13 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, IVS8, A-G, -26
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199469650,
|
|
|
|
|
|
|
|
ClinVar: RCV000023252, RCV000128488, RCV004700408
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 families, 3 with de novo occurrence of pseudohypoaldosteronism, type IIE (PHA2E; 614496), Boyden et al. (2012) identified an A-to-G transition at the -26 position of the intron 8 splice acceptor site in the CUL3 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, IVS8, T-G, -28
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199469649,
|
|
|
|
|
|
gnomAD: rs199469649,
|
|
|
|
|
|
ClinVar: RCV000023253, RCV000128489
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family segregating autosomal dominant pseudohypoaldosteronism type IIE (PHA2E; 614496), Boyden et al. (2012) identified an T-to-G transversion at the -28 position of the intron 8 splice branch point in the CUL3 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, IVS8, T-G, -12
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199469651,
|
|
|
|
|
|
|
|
ClinVar: RCV000023254, RCV000128486
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with pseudohypoaldosteronism type IIE (PHA2E; 614496), Boyden et al. (2012) identified an T-to-G transversion in the CUL3 gene, at the -12 position of the intron 8 splice acceptor site, within the polypyrimidine tract. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, IVS8, T-A, -5
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199469652,
|
|
|
|
|
|
|
|
ClinVar: RCV000023255, RCV000128491
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a de novo case of pseudohypoaldosteronism type IIE (PHA2E; 614496), Boyden et al. (2012) identified an T-to-A transversion in the CUL3 gene, at the -5 position of the intron 8 splice acceptor site, within the polypyrimidine tract. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, IVS8, C-T, -3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199469653,
|
|
|
|
|
|
|
|
ClinVar: RCV000023256, RCV000128490
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a de novo case of pseudohypoaldosteronism type IIE (PHA2E; 614496), Boyden et al. (2012) identified a C-to-T transition at the -3 position of the intron 8 splice acceptor site of the CUL3 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, IVS8, G-A, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199469654,
|
|
|
|
|
|
|
|
ClinVar: RCV000023257, RCV000128487
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected members of a 2-generation family with pseudohypoaldosteronism type IIE (PHA2E; 614496), Boyden et al. (2012) identified a G-to-A transition in the CUL3 gene, at the -1 position of the intron 8 splice acceptor site. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 PSEUDOHYPOALDOSTERONISM, TYPE IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, ASP413GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199469656,
|
|
|
|
|
|
|
|
ClinVar: RCV000023258, RCV000128493
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 families with undetermined pseudohypoaldosteronism type IIE (PHA2E; 614496), Boyden et al. (2012) identified an A-to-G transition resulting in an asp-to-gly substitution at codon 413 (D413G) within exon 9 of the CUL3 gene that resulted in an ES enhancer. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM OR SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, TYR58CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1553535841,
|
|
|
|
|
|
|
|
ClinVar: RCV000677281, RCV000987041, RCV001352922
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-year-old boy (family 2) with neurodevelopmental disorder without seizures or autism (NEDAUS; 619239), Thiffault et al. (2018) identified a de novo heterozygous c.173A-G transition in the CUL3 gene, resulting in a tyr58-to-cys (Y58C) substitution. The mutation, which was found by trio-based next-generation sequencing, was considered to be pathogenic after curation using a point-based system. Functional studies of the variant were not performed. The child had failure to thrive, microcephaly, speech delay, and absent thumb. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 NEURODEVELOPMENTAL DISORDER WITH AUTISM WITHOUT SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, SER133TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs981700726,
|
|
|
|
|
|
|
|
ClinVar: RCV001352923
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 12-year-old Brazilian girl (F1389-1) with neurodevelopmental disorder with autism but without seizures (NEDAUS; 619239), da Silva Montenegro et al. (2020) identified a de novo heterozygous c.398C-G transversion (c.398C-G, NM_001257197) in exon 4 of the CUL3 gene, resulting in a ser133-to-ter (S133X) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was classified as pathogenic according to ACMG criteria. The patient had autism spectrum disorder, with mild motor and speech delay. She did not have seizures. Functional studies of the variant were not performed, but it was predicted to result in a loss of function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM WITH SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, VAL285ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1343840421,
|
|
|
|
|
|
gnomAD: rs1343840421,
|
|
|
|
|
|
ClinVar: RCV001352924
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-year-old Japanese girl (patient 1) with neurodevelopmental disorder without autism but with seizures (NEDAUS; 619239), Nakashima et al. (2020) identified a de novo heterozygous c.854T-C transition (c.854T-C, NM_003590.4) in the CUL3 gene, resulting in a val285-to-ala (V285A) substitution in the CR3 domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 153) or gnomAD databases. In vitro functional expression studies showed that the mutant protein had significantly weaker interaction with KEAP1 (606016) compared to wildtype, suggesting that it caused instability of the CRL complex. The patient had onset of intractable spasms and tonic seizures at 2 months of age. EEG showed a suppression-burst pattern, consistent with West syndrome. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM WITH SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, 1-BP DEL, 137G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1694759979,
|
|
|
|
|
|
|
|
ClinVar: RCV001352925
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-year-old Malaysian boy (patient 2) with neurodevelopmental disorder without autism but with seizures (NEDAUS; 619239), Nakashima et al. (2020) identified a de novo heterozygous 1-bp deletion (c.137delG, NM_003590.4), resulting in a frameshift and premature termination (Arg46LeufsTer32). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 153) or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to result in a loss of function and haploinsufficiency. The patient had onset of intractable seizures at 6 months of age; EEG showed hypsarrhythmia, consistent with West syndrome. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM OR SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, 1-BP DEL, NT1239
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1692487571,
|
|
|
|
|
|
|
|
ClinVar: RCV001352926
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old Dutch girl (patient 3) with neurodevelopmental disorder without autism or seizures (NEDAUS; 619239), Nakashima et al. (2020) identified a de novo heterozygous 1-bp deletion (c.1239del, NM_003590.4) in the CUL3 gene, resulting in a frameshift and premature termination (Asp413GlufsTer42). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 153) or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to result in a loss of function and haploinsufficiency. The patient had mild intellectual disability with poor speech. She did not have seizures. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 NEURODEVELOPMENTAL DISORDER WITH AUTISM AND SEIZURES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CUL3, 2-BP INS, 1758TG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1692153577,
|
|
|
|
|
|
|
|
ClinVar: RCV001352927
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old Japanese girl with neurodevelopmental disorder with autism and seizures (NEDAUS; 619239), Iwafuchi et al. (2021) identified a de novo heterozygous 2-bp insertion (c.1758_1759insTG, NM_003590.5) in exon 13 of the CUL3 gene, resulting in a frameshift and premature termination (Thr587Ter). The mutation, which was found whole-exome sequencing and confirmed by Sanger sequencing, was not present in the gnomAD database. The mutation was predicted to lead to nonsense-mediated mRNA decay and haploinsufficiency. Functional studies of the variant were not performed. The patient presented at age 21 months with status epilepticus and thereafter showed developmental regression with loss of eye contact, autistic features, and features of Rett syndrome (RTT; 312750). </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">
|
|
Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., and 34 others.
|
|
<strong>Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.</strong>
|
|
Nature 482: 98-102, 2012.
|
|
|
|
|
|
[PubMed: 22266938]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10814]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Canning, P., Cooper, C. D. O., Krojer, T., Murray, J. W., Pike, A. C. W., Chaikuad, A., Keates, T., Thangaratnarajah, C., Hojzan, V., Ayinampudi, V., Marsden, B. D., Gileadi, O., Knapp, S., von Delft, F., Bullock, A. N.
|
|
<strong>Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases.</strong>
|
|
J. Biol. Chem. 288: 7803-7814, 2013. Note: Erratum: J. Biol. Chem. 288: 28304 only, 2013.
|
|
|
|
|
|
[PubMed: 23349464]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M112.437996]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cummings, C. M., Bentley, C. A., Perdue, S. A., Baas, P. W., Singer, J. D.
|
|
<strong>The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal mitosis in mammalian cells.</strong>
|
|
J. Biol. Chem. 284: 11663-11675, 2009.
|
|
|
|
|
|
[PubMed: 19261606]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M809374200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
da Silva Montenegro, E. M., Costa, C. S., Campos, G., Scliar, M., de Almeida, T. F., Zachi, E. C., Silva, I. M. W., Chan, A. J. S., Zarrei, M., Lourenco, N. C. V., Yamamoto, G. L., Scherer, S., Passos-Bueno, M. R.
|
|
<strong>Meta-analyses support previous and novel autism candidate genes: outcomes of an unexplored Brazilian cohort.</strong>
|
|
Autism Res. 13: 199-206, 2020.
|
|
|
|
|
|
[PubMed: 31696658]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/aur.2238]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dong, Z., Chen, W., Chen, C., Wang, H., Cui, W., Tan, Z., Robinson, H., Gao, N., Luo, B., Zhang, L., Zhao, K., Xiong, W.-C., Mei, L.
|
|
<strong>CUL3 deficiency causes social deficits and anxiety-like behaviors by impairing excitation-inhibition balance through the promotion of Cap-dependent translation.</strong>
|
|
Neuron 105: 475-490, 2020.
|
|
|
|
|
|
[PubMed: 31780330]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neuron.2019.10.035]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Du, M., Sansores-Garcia, L., Zu, Z., Wu, K. K.
|
|
<strong>Cloning and expression analysis of a novel salicylate suppressible gene, Hs-CUL-3, a member of cullin/Cdc53 family.</strong>
|
|
J. Biol. Chem. 273: 24289-24292, 1998.
|
|
|
|
|
|
[PubMed: 9733711]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.273.38.24289]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hartz, P. A.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 3/14/2012.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ishikawa, K., Nagase, T., Suyama, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
|
|
<strong>Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong>
|
|
DNA Res. 5: 169-176, 1998.
|
|
|
|
|
|
[PubMed: 9734811]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/dnares/5.3.169]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iwafuchi, S., Kikuchi, A., Endo, W., Inui, T., Aihara, Y., Satou, K., Kaname, T., Kure, S.
|
|
<strong>A novel stop-gain CUL3 mutation in a Japanese patient with autism spectrum disorder.</strong>
|
|
Brain Dev. 43: 303-307, 2021.
|
|
|
|
|
|
[PubMed: 33097317]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.braindev.2020.09.015]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jin, L., Pahuja, K. B., Wickliffe, K. E., Gorur, A., Baumgartel, C., Schekman, R., Rape, M.
|
|
<strong>Ubiquitin-dependent regulation of COPII coat size and function.</strong>
|
|
Nature 482: 495-500, 2012.
|
|
|
|
|
|
[PubMed: 22358839]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10822]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kipreos, E. T., Lander, L. E., Wing, J. P., He, W. W., Hedgecock, E. M.
|
|
<strong>cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family.</strong>
|
|
Cell 85: 829-839, 1996.
|
|
|
|
|
|
[PubMed: 8681378]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81267-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kong, A., Frigge, M. L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., Gudjonsson, S. A., Sigurdsson, A., Jonasdottir, A., Jonasdottir, A., Wong, W. S. W., Sigurdsson, G., and 9 others.
|
|
<strong>Rate of de novo mutations and the importance of father's age to disease risk.</strong>
|
|
Nature 488: 471-475, 2012.
|
|
|
|
|
|
[PubMed: 22914163]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11396]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maerki, S., Olma, M. H., Staubli, T., Steigemann, P., Gerlich, D. W., Quadroni, M., Sumara, I., Peter, M.
|
|
<strong>The Cul3-KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis.</strong>
|
|
J. Cell Biol. 187: 791-800, 2009.
|
|
|
|
|
|
[PubMed: 19995937]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1083/jcb.200906117]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mathew, R., Seiler, M. P., Scanlon, S. T., Mao, A., Constantinides, M. G., Bertozzi-Villa, C., Singer, J. D., Bendelac, A.
|
|
<strong>BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs.</strong>
|
|
Nature 491: 618-621, 2012.
|
|
|
|
|
|
[PubMed: 23086144]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11548]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Michel, J. J., Xiong, Y.
|
|
<strong>Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A.</strong>
|
|
Cell Growth Differ. 9: 435-449, 1998.
|
|
|
|
|
|
[PubMed: 9663463]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakashima, M., Kato, M., Matsukura, M., Kira, R., Ngu, L.-H., Lichtenbelt, K. D., van Gassen, K. L. I., Mitsuhashi, S., Saitsu, H., Matsumoto, N.
|
|
<strong>De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms.</strong>
|
|
J. Hum. Genet. 65: 727-734, 2020.
|
|
|
|
|
|
[PubMed: 32341456]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s10038-020-0758-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Papizan, J. B., Vidal, A. H., Bezprozvannaya, S., Bassel-Duby, R., Olson, E. N.
|
|
<strong>Cullin-3-RING ubiquitin ligase activity is required for striated muscle function in mice.</strong>
|
|
J. Biol. Chem. 293: 8802-8811, 2018.
|
|
|
|
|
|
[PubMed: 29653945]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.RA118.002104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rondou, P., Haegeman, G., Vanhoenacker, P., Van Craenenbroeck, K.
|
|
<strong>BTB protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase.</strong>
|
|
J. Biol. Chem. 283: 11083-11096, 2008.
|
|
|
|
|
|
[PubMed: 18303015]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M708473200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sumara, I., Quadroni, M., Frei, C., Olma, M. H., Sumara, G., Ricci, R., Peter, M.
|
|
<strong>A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells.</strong>
|
|
Dev. Cell 12: 887-900, 2007.
|
|
|
|
|
|
[PubMed: 17543862]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.devcel.2007.03.019]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thiffault, I., Cadieux-Dion, M., Farrow, E., Caylor, R., Miller, N., Soden, S., Saunders, C.
|
|
<strong>On the verge of diagnosis: detection, reporting, and investigation of de novo variants in novel genes identified by clinical sequencing.</strong>
|
|
Hum. Mutat. 39: 1505-1516, 2018.
|
|
|
|
|
|
[PubMed: 30311385]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.23646]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tian, M., Hao, F., Jin, X., Sun, X., Jiang, Y., Wang, Y., Li, D., Chang, T., Zou, Y., Peng, P., Xia, C., Liu, J., Li, Y., Wang, P., Feng, Y., Wei, M.
|
|
<strong>ACLY ubiquitination by CUL3-KLHL25 induces the reprogramming of fatty acid metabolism to facilitate iTreg differentiation.</strong>
|
|
eLife 10: e62394, 2021.
|
|
|
|
|
|
[PubMed: 34491895]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7554/eLife.62394]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Werner, A., Iwasaki, S., McGourty, C. A., Medina-Ruiz, S., Teerikorpi, N., Fedrigo, I., Ingolia, N. T., Rape, M.
|
|
<strong>Cell-fate determination by ubiquitin-dependent regulation of translation.</strong>
|
|
Nature 525: 523-527, 2015.
|
|
|
|
|
|
[PubMed: 26399832]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature14978]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, C., Liu, J., Huang, G., Zhao, Y., Yue, X., Wu, H., Li, J., Zhu, J., Shen, Z., Haffty, B. G., Hu, W., Feng, Z.
|
|
<strong>Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression.</strong>
|
|
Genes Dev. 30: 1956-1970, 2016.
|
|
|
|
|
|
[PubMed: 27664236]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.283283.116]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., Tan, Y., Ci, Y., Wu, F., Dai, X., Guo, J., Huang, Y.-H., Fan, C., Ren, S., Sun, Y., Freeman, G. J., Sicinski, P., Wei, W.
|
|
<strong>Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance.</strong>
|
|
Nature 553: 91-95, 2018. Note: Erratum: Nature 571: E10, 2019.
|
|
|
|
|
|
[PubMed: 29160310]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature25015]
|
|
|
|
|
|
</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">
|
|
Bao Lige - updated : 05/25/2022<br>Cassandra L. Kniffin - updated : 03/18/2021<br>Bao Lige - updated : 11/02/2020<br>Bao Lige - updated : 06/22/2020<br>Bao Lige - updated : 05/13/2020<br>Bao Lige - updated : 07/11/2019<br>Ada Hamosh - updated : 04/12/2018<br>Patricia A. Hartz - updated : 10/21/2015<br>Patricia A. Hartz - updated : 3/10/2015<br>Ada Hamosh - updated : 12/13/2012<br>Patricia A. Hartz - updated : 3/14/2012<br>Patricia A. Hartz - updated : 3/8/2012<br>Ada Hamosh - updated : 2/22/2012<br>Patricia A. Hartz - updated : 6/26/2007
|
|
</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">
|
|
Rebekah S. Rasooly : 10/13/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
mgross : 05/25/2022<br>alopez : 04/14/2021<br>carol : 03/25/2021<br>alopez : 03/24/2021<br>ckniffin : 03/18/2021<br>mgross : 11/02/2020<br>mgross : 06/22/2020<br>mgross : 06/04/2020<br>mgross : 05/13/2020<br>carol : 10/03/2019<br>mgross : 07/11/2019<br>mgross : 06/21/2018<br>mgross : 06/21/2018<br>alopez : 04/12/2018<br>carol : 02/09/2018<br>mgross : 10/21/2015<br>mgross : 3/11/2015<br>mcolton : 3/10/2015<br>alopez : 12/21/2012<br>terry : 12/13/2012<br>mgross : 5/23/2012<br>terry : 3/14/2012<br>mgross : 3/8/2012<br>terry : 3/8/2012<br>alopez : 2/27/2012<br>terry : 2/22/2012<br>mgross : 7/12/2007<br>terry : 6/26/2007<br>alopez : 10/30/1998<br>dkim : 10/28/1998<br>alopez : 10/13/1998
|
|
</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>
|
|
|
|
|