2998 lines
240 KiB
Text
2998 lines
240 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
|
|
|
|
- *604433 - POTASSIUM CHANNEL, VOLTAGE-GATED, ISK-RELATED SUBFAMILY, MEMBER 3; KCNE3
|
|
|
|
|
|
- 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=604433"><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">*604433</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/604433">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=ENSG00000175538;t=ENST00000310128" 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=10008" 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=604433" 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=ENSG00000175538;t=ENST00000310128" 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_005472,XM_011544713,XM_017017047,XM_017017048,XM_017017049,XM_017017051,XM_047426176,XM_047426177" 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_005472" 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=604433" 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=07256&isoform_id=07256_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/KCNE3" 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/4704429,4885443,7387903,10304442,48146535,60219512,77632644,77632646,83405061,88683041,119595344,146048345,189053195,767967373,1034571509,1034571511,1034571513,1034571517,2217280645,2217280650,2462522288,2462522290,2462522292,2462522294,2462522296,2462522298" 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/Q9Y6H6" 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=10008" 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=ENSG00000175538;t=ENST00000310128" 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=KCNE3" 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=KCNE3" 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+10008" 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/KCNE3" 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:10008" 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/10008" 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=chr11&hgg_gene=ENST00000310128.9&hgg_start=74454841&hgg_end=74467549&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:6243" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604433[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=604433[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000175538" 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=KCNE3" 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=KCNE3" 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=KCNE3" 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=KCNE3&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/PA393" 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:6243" 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://www.mousephenotype.org/data/genes/MGI:1891124" 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/KCNE3#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:1891124" 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/10008/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=10008" 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>
|
|
</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:10008" 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=KCNE3&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>
|
|
604433
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
POTASSIUM CHANNEL, VOLTAGE-GATED, ISK-RELATED SUBFAMILY, MEMBER 3; KCNE3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
MINIMUM POTASSIUM ION CHANNEL-RELATED PEPTIDE 2; MIRP2<br />
|
|
MINK-RELATED PEPTIDE 2
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=KCNE3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">KCNE3</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/11/746?start=-3&limit=10&highlight=746">11q13.4</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:74454841-74467549&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'})">11:74,454,841-74,467,549</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/746?start=-3&limit=10&highlight=746">
|
|
11q13.4
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Brugada syndrome 6
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613119"> 613119 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</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/604433" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/604433" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#3" class="mim-tip-reference" title="Abbott, G. W., Sesti, F., Splawski, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N. <strong>MiRP1 forms I(Kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong> Cell 97: 175-187, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10219239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10219239</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80728-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10219239">Abbott et al. (1999)</a> cloned the potassium channel beta subunit KCNE3 by homology to KCNE1 (<a href="/entry/176261">176261</a>). KCNE3 is a 103-amino acid protein with a relative molecular mass of about 12 kD that displays roughly 35% identity to other KCNE proteins within the single transmembrane domain and a following short stretch. Northern blot analysis revealed a prominent band in the kidney, moderate expression in the small intestine, and weaker bands in most other tissues, including colon and heart. By Northern blot analysis, <a href="#1" class="mim-tip-reference" title="Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N. <strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong> Cell 104: 217-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11207363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11207363</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00207-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11207363">Abbott et al. (2001)</a> detected KCNE3 mRNA in skeletal muscle, but not in small intestine, colon, kidney, or liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10219239+11207363" 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 radiation hybrid analysis, <a href="#1" class="mim-tip-reference" title="Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N. <strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong> Cell 104: 217-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11207363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11207363</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00207-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11207363">Abbott et al. (2001)</a> mapped the KCNE3 gene to chromosome 11q13-q14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11207363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>When KCNQ1 (<a href="/entry/607542">607542</a>) interacts with the beta subunit KCNE1, a slow depolarization-activated potassium current I(Ks) is formed that is affected in some forms of cardiac arrhythmia. <a href="#11" class="mim-tip-reference" title="Schroeder, B. C., Waldegger, S., Fehr, S., Bleich, M., Warth, R., Greger, R., Jentsch, T. J. <strong>A constitutively open potassium channel formed by KCNQ1 and KCNE3.</strong> Nature 403: 196-199, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10646604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10646604</a>] [<a href="https://doi.org/10.1038/35003200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10646604">Schroeder et al. (2000)</a> demonstrated that the beta subunit KCNE3 markedly changes KCNQ1 properties to yield currents that are nearly instantaneous and depend linearly on voltage. KCNE3 also suppresses the currents of KCNQ4 (<a href="/entry/603537">603537</a>) and HERG (see <a href="/entry/152427">152427</a>) potassium channels. In the intestine, KCNQ1 and KCNE3 mRNAs colocalized in crypt cells. This localization, and the pharmacology, voltage dependence, and stimulation by cyclic AMP of KCNQ1/KCNE3 currents, indicated that these proteins may assemble to form the potassium channel that is important for cyclic AMP-stimulated intestinal chloride secretion and that is involved in secretory diarrhea and cystic fibrosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10646604" 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 skeletal muscle cells, <a href="#1" class="mim-tip-reference" title="Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N. <strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong> Cell 104: 217-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11207363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11207363</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00207-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11207363">Abbott et al. (2001)</a> demonstrated that KCNE3 forms stable complexes with the pore-forming unit Kv3.4 (KCNC4; <a href="/entry/176265">176265</a>), resulting in potassium channels with increased conductance, faster recovery from inactivation, and slower cumulative inactivation. KCNE3-KCNE4 channels are 80-fold more active at -40 mv and establish the resting membrane potential of skeletal muscle cells. Western blot analysis detected the KCNE3 protein in skeletal muscle plasma membranes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11207363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Melman, Y. F., Um, S. Y., Krumerman, A., Kagan, A., McDonald, T. V. <strong>KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity.</strong> Neuron 42: 927-937, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15207237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15207237</a>] [<a href="https://doi.org/10.1016/j.neuron.2004.06.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15207237">Melman et al. (2004)</a> showed that KCNE1 and KCNE3 associate with an extended binding interface of KCNQ1 that includes structures within the channel pore and C terminus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15207237" 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>Brugada Syndrome 6</em></strong></p><p>
|
|
<a href="#4" class="mim-tip-reference" title="Delpon, E., Cordeiro, J. M., Nunez, L., Thomsen, P. E. B., Guerchicoff, A., Pollevick, G. D., Wu, Y., Kanters, J. K., Larsen, C. T., Hofman-Bang, J., Burashnikov, E., Christiansen, M., Antzelevitch, C. <strong>Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome.</strong> Circ. Arrhythm. Electrophysiol. 1: 209-218, 2008. Note: Erratum: Circ. Arrhythm. Electrophysiol. 1: e2, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19122847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19122847</a>] [<a href="https://doi.org/10.1161/CIRCEP.107.748103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19122847">Delpon et al. (2008)</a> sequentially screened 14 ion channel genes in 105 probands with Brugada syndrome (see <a href="/entry/601144">601144</a>) and identified a heterozygous mutation in the KCNE3 gene (R99H; <a href="#0002">604433.0002</a>) in a proband from a Danish pedigree (Brugada syndrome-6; BRGDA6, <a href="/entry/613119">613119</a>). Cotransfection of R99H-mutant KCNE3 with KCNQ1 (<a href="/entry/607542">607542</a>) produced no alteration in tail current magnitude or kinetics, whereas cotransfection of R99H-mutant KCNE3 with KCND3 (<a href="/entry/605411">605411</a>) resulted in a significant increase in the transient outward current intensity compared to wildtype. The authors also demonstrated coimmunoprecipitation of Kv4.3 and KCNE3 in human left atrial appendage tissue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19122847" 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 40 consecutive Japanese patients with a Brugada-like pattern on electrocardiography, <a href="#9" class="mim-tip-reference" title="Nakajima, T., Wu, J., Kaneko, Y., Ashihara, T., Ohno, S., Irie, T., Ding, W.-G., Matsuura, H., Kurabayashi, M., Horie, M. <strong>KCNE3 T4A as the genetic basis of Brugada-pattern electrocardiogram.</strong> Circ. J. 76: 2763-2772, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22987075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22987075</a>] [<a href="https://doi.org/10.1253/circj.cj-12-0551" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22987075">Nakajima et al. (2012)</a> analyzed all coding exons of the SCN5A (<a href="/entry/600163">600163</a>), SCN1B (<a href="/entry/600235">600235</a>), SCN3B (<a href="/entry/608214">608214</a>), KCNE5 (<a href="/entry/300328">300328</a>), and KCNE3 genes, and identified a 55-year-old man who was heterozygous for a T4A mutation in KCNE3 (<a href="#0003">604433.0003</a>) and negative for mutation in the other 4 genes as well as in the CACNA1C (<a href="/entry/114205">114205</a>) and CACNB2 (<a href="/entry/600003">600003</a>) genes. Functional analysis demonstrated a significantly increased current density with the T4A mutant compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22987075" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Possible Role in Periodic Paralysis</em></strong></p><p>
|
|
Although <a href="#1" class="mim-tip-reference" title="Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N. <strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong> Cell 104: 217-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11207363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11207363</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00207-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11207363">Abbott et al. (2001)</a> identified an arg83-to-his (R83H; <a href="#0001">604433.0001</a>) substitution in 2 of 100 patients with hyperkalemic periodic paralysis (HYPP; <a href="/entry/170500">170500</a>) and hypokalemic periodic paralysis (HOKPP; <a href="/entry/170400">170400</a>), respectively, <a href="#12" class="mim-tip-reference" title="Sternberg, D., Tabti, N., Fournier, E., Hainque, B., Fontaine, B. <strong>Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis.</strong> Neurology 61: 857-859, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14504341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14504341</a>] [<a href="https://doi.org/10.1212/01.wnl.0000082392.66713.e3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14504341">Sternberg et al. (2003)</a> and <a href="#6" class="mim-tip-reference" title="Jurkat-Rott, K., Lehmann-Horn, F. <strong>Periodic paralysis mutation MiRP2-R83H in controls: interpretations and general recommendation.</strong> Neurology 62: 1012-1015, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15037716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15037716</a>] [<a href="https://doi.org/10.1212/01.wnl.0000119392.29624.88" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15037716">Jurkat-Rott and Lehmann-Horn (2004)</a> concluded that the R83H variant does not play a causative role in periodic paralysis. See <a href="#0001">604433.0001</a> for detailed discussion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14504341+15037716+11207363" 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="Dias Da Silva, M. R., Cerutti, J. M., Arnaldi, L. A. T., Maciel, R. M. B. <strong>A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis.</strong> J. Clin. Endocr. Metab. 87: 4881-4884, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12414843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12414843</a>] [<a href="https://doi.org/10.1210/jc.2002-020698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12414843">Dias Da Silva et al. (2002)</a> identified the R83H variant in a sporadic case of thyrotoxic periodic paralysis (TPP; <a href="/entry/188580">188580</a>). The patient was a 44-year-old Caucasian man of Portuguese descent who had experienced episodic paralysis for 2 years before developing signs of thyrotoxicosis caused by Graves disease (<a href="/entry/275000">275000</a>). <a href="#13" class="mim-tip-reference" title="Tang, N. L. S., Chow, C. C., Ko, G. T. C., Tai, M. H. L., Kwok, R., Yao, X. Q., Cockram, C. S. <strong>No mutation in the KCNE3 potassium channel gene in Chinese thyrotoxic hypokalaemic periodic paralysis patients.</strong> Clin. Endocr. 61: 109-112, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15212652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15212652</a>] [<a href="https://doi.org/10.1111/j.1365-2265.2004.02079.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15212652">Tang et al. (2004)</a> did not identify the R83H substitution, or any mutations in the KCNE3 gene, among 79 Chinese patients with thyrotoxic hypokalemic periodic paralysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12414843+15212652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Possible Role in Acquired Long QT Syndrome</em></strong></p><p>
|
|
In 485 Japanese probands with congenital or acquired long QT syndrome (see LQT1, <a href="/entry/192500">192500</a>), who on electrocardiography exhibited QT interval prolongation of 460 ms or more or who had documented torsade de pointes, <a href="#10" class="mim-tip-reference" title="Ohno, S., Toyoda, F., Zankov, D. P., Yoshida, H., Makiyama, T., Tsuji, K., Honda, T., Obayashi, K., Ueyama, H., Shimizu, W., Miyamoto, Y., Kamakura, S., Matsuura, H., Kita, T., Horie, M. <strong>Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome.</strong> Hum. Mutat. 30: 557-563, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19306396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19306396</a>] [<a href="https://doi.org/10.1002/humu.20834" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19306396">Ohno et al. (2009)</a> analyzed 5 known LQT genes (KCNQ1, <a href="/entry/607542">607542</a>; KCNH2, <a href="/entry/152427">152427</a>; SCN5A, <a href="/entry/600163">600163</a>; KCNE1, <a href="/entry/176261">176261</a>; and KCNE2, <a href="/entry/603796">603796</a>) as well as the candidate gene KCNE3. A 76-year-old woman with acquired LQT who was negative for mutation in the 5 known LQT genes was found to be heterozygous for the R99H missense mutation in KCNE3 (<a href="#0002">604433.0002</a>), previously associated with Brugada syndrome. In another 2 unrelated probands with LQT, <a href="#10" class="mim-tip-reference" title="Ohno, S., Toyoda, F., Zankov, D. P., Yoshida, H., Makiyama, T., Tsuji, K., Honda, T., Obayashi, K., Ueyama, H., Shimizu, W., Miyamoto, Y., Kamakura, S., Matsuura, H., Kita, T., Horie, M. <strong>Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome.</strong> Hum. Mutat. 30: 557-563, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19306396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19306396</a>] [<a href="https://doi.org/10.1002/humu.20834" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19306396">Ohno et al. (2009)</a> identified a different missense mutation in KCNE3 (T4A; <a href="#0003">604433.0003</a>); however, in 1 family, the proband and his asymptomatic mother and sister were also heterozygous for a known LQT-associated variant in the KCNH2 gene (G572S), and electrophysiologic analysis showed that the KCNE3 T4A variant did not have a statistically significant effect on current density. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19306396" 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>3 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/604433" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=604433[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 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KCNE3, ARG83HIS
|
|
</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> rs17215437 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs17215437;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/rs17215437?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=rs17215437" 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=rs17215437" 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=RCV000005879 OR RCV000171813 OR RCV000223897 OR RCV000253742 OR RCV000415218 OR RCV000538199 OR RCV000852657 OR RCV000988595" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005879, RCV000171813, RCV000223897, RCV000253742, RCV000415218, RCV000538199, RCV000852657, RCV000988595" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005879...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled HYPOKALEMIC PERIODIC PARALYSIS, HYPERKALEMIC PERIODIC PARALYSIS, and SUSCEPTIBILITY TO THYROTOXIC PERIODIC PARALYSIS based on the findings of <a href="#1" class="mim-tip-reference" title="Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N. <strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong> Cell 104: 217-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11207363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11207363</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00207-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11207363">Abbott et al. (2001)</a> and <a href="#5" class="mim-tip-reference" title="Dias Da Silva, M. R., Cerutti, J. M., Arnaldi, L. A. T., Maciel, R. M. B. <strong>A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis.</strong> J. Clin. Endocr. Metab. 87: 4881-4884, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12414843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12414843</a>] [<a href="https://doi.org/10.1210/jc.2002-020698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12414843">Dias Da Silva et al. (2002)</a>, has been reclassified based on the findings of <a href="#12" class="mim-tip-reference" title="Sternberg, D., Tabti, N., Fournier, E., Hainque, B., Fontaine, B. <strong>Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis.</strong> Neurology 61: 857-859, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14504341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14504341</a>] [<a href="https://doi.org/10.1212/01.wnl.0000082392.66713.e3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14504341">Sternberg et al. (2003)</a> and <a href="#6" class="mim-tip-reference" title="Jurkat-Rott, K., Lehmann-Horn, F. <strong>Periodic paralysis mutation MiRP2-R83H in controls: interpretations and general recommendation.</strong> Neurology 62: 1012-1015, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15037716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15037716</a>] [<a href="https://doi.org/10.1212/01.wnl.0000119392.29624.88" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15037716">Jurkat-Rott and Lehmann-Horn (2004)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14504341+12414843+15037716+11207363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N. <strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong> Cell 104: 217-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11207363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11207363</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00207-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11207363">Abbott et al. (2001)</a> identified a 340G-A transition in the KCNE3 gene, resulting in an arg83-to-his (R83H) substitution in 2 of 100 patients with atypical forms of hyperkalemic periodic paralysis (HYPP; <a href="/entry/170500">170500</a>) and hypokalemic periodic paralysis (HOKPP; <a href="/entry/170400">170400</a>), respectively. However, <a href="#12" class="mim-tip-reference" title="Sternberg, D., Tabti, N., Fournier, E., Hainque, B., Fontaine, B. <strong>Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis.</strong> Neurology 61: 857-859, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14504341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14504341</a>] [<a href="https://doi.org/10.1212/01.wnl.0000082392.66713.e3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14504341">Sternberg et al. (2003)</a> and <a href="#6" class="mim-tip-reference" title="Jurkat-Rott, K., Lehmann-Horn, F. <strong>Periodic paralysis mutation MiRP2-R83H in controls: interpretations and general recommendation.</strong> Neurology 62: 1012-1015, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15037716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15037716</a>] [<a href="https://doi.org/10.1212/01.wnl.0000119392.29624.88" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15037716">Jurkat-Rott and Lehmann-Horn (2004)</a> concluded that the R83H variant does not play a causative role in periodic paralysis and that it is a polymorphism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14504341+15037716+11207363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N. <strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong> Cell 104: 217-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11207363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11207363</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00207-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11207363">Abbott et al. (2001)</a> reported a male proband with atypical HYPP who was negative for mutations in the SCN4A gene and who carried the R83H variant. He presented at 22 months of age with episodic weakness of the extremities. Most episodes came on during sleep and were brief (12 hours), although they occasionally lasted for days. Serum potassium levels during attacks were normal. High carbohydrate meals helped resolve attacks, and treatment with a carbonic anhydrase inhibitor prevented attacks. The age at onset, frequent nature of attacks, and improvement with carbohydrate loading were all consistent with HYPP; however, provocative testing with potassium had not been performed. Frequent attacks upon awakening and absence of myotonia were considered atypical for this diagnosis. <a href="#1" class="mim-tip-reference" title="Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N. <strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong> Cell 104: 217-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11207363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11207363</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00207-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11207363">Abbott et al. (2001)</a> reported a male proband with atypical HOKPP who was negative for mutations in the SCN4A and CACNA1S genes and who carried the R83H variant. He had onset of episodic paralytic weakness at the age of 14 years. Episodes were characterized by weakness primarily affecting the lower extremities and lasting hours to days, and were usually precipitated by strenuous exercise followed by rest or after prolonged sitting. Carbohydrate ingestion did not precipitate attacks, alcohol intake appeared to facilitate recovery from an attack, and potassium had no effect. He was classified as having hypokalemic periodic paralysis because of the typical age of onset, paralytic attacks that most often occurred after exercise, a low potassium level during a spontaneous attack, and the ability to precipitate an attack with insulin and glucose on 1 occasion. Atypical for this diagnosis was that a second provocative test was negative and that attacks usually occurred while awake. The variant was not found in DNA from a control population of 120 unaffected individuals, suggesting to them that it does not represent a polymorphism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11207363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N. <strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong> Cell 104: 217-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11207363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11207363</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00207-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11207363">Abbott et al. (2001)</a> reported functional expression studies that showed that the mutant R83H KCNE3-Kv3.4 complexes exhibited reduced current density and diminished capacity to set resting membrane potential as a dominant-negative effect compared to wildtype. In in vitro studies, <a href="#2" class="mim-tip-reference" title="Abbott, G. W., Butler, M. H., Goldstein, S. A. N. <strong>Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis.</strong> FASEB J. 20: 293-301, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16449802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16449802</a>] [<a href="https://doi.org/10.1096/fj.05-5070com" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16449802">Abbott et al. (2006)</a> found that the R83H variant shifts the voltage-dependence of channel activation in response to pH change. The current through the mutant channel decreased compared to wildtype as intracellular pH was lowered. The authors suggested that R83H acts as a regulatory domain, and concluded that the variation may predispose to the development of periodic paralysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11207363+16449802" 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 contrast, <a href="#12" class="mim-tip-reference" title="Sternberg, D., Tabti, N., Fournier, E., Hainque, B., Fontaine, B. <strong>Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis.</strong> Neurology 61: 857-859, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14504341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14504341</a>] [<a href="https://doi.org/10.1212/01.wnl.0000082392.66713.e3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14504341">Sternberg et al. (2003)</a> did not identify the R83H mutation in 64 probands with either HYPP or HOKPP in whom mutations in the SCN4A and CACNA1S genes had been excluded. One patient with HOKPP had the R83H change, but he also had a mutation in the SCN4A gene (R672H; <a href="/entry/603967#0016">603967.0016</a>). His father, who had the same clinical phenotype and the SCN4A mutation, did not carry the R83H mutation, whereas the asymptomatic mother carried the R83H variant. The findings yielded a frequency of 0.0096 in patients with periodic paralysis (1 in 104) and 0.0158 (8 of 506) in healthy controls. Likewise, <a href="#6" class="mim-tip-reference" title="Jurkat-Rott, K., Lehmann-Horn, F. <strong>Periodic paralysis mutation MiRP2-R83H in controls: interpretations and general recommendation.</strong> Neurology 62: 1012-1015, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15037716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15037716</a>] [<a href="https://doi.org/10.1212/01.wnl.0000119392.29624.88" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15037716">Jurkat-Rott and Lehmann-Horn (2004)</a> identified the R83H mutation in 1 of 76 patients with HYPP, in 1 of 61 patients with paramyotonia congenita (<a href="/entry/608390">608390</a>), in 5 unaffected relatives, in 0 of 8 patients with TTPP, and in 3 of 321 healthy controls, suggesting that it is a polymorphism. Provocation of an unaffected carrier with glucose or potassium administration did not induce weakness. The authors offered a formula for determining causality of a mutation based on reduced penetrance, but concluded that the R83H mutation does not cause these muscle disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14504341+15037716" 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="Dias Da Silva, M. R., Cerutti, J. M., Arnaldi, L. A. T., Maciel, R. M. B. <strong>A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis.</strong> J. Clin. Endocr. Metab. 87: 4881-4884, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12414843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12414843</a>] [<a href="https://doi.org/10.1210/jc.2002-020698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12414843">Dias Da Silva et al. (2002)</a> identified the R83H substitution in 1 of 15 patients with thyrotoxic hypokalemic periodic paralysis (<a href="/entry/188580">188580</a>). The patient was a 44-year-old Caucasian man of Portuguese descent who experienced episodic paralysis for 2 years before developing thyrotoxicosis caused by Graves disease (<a href="/entry/275000">275000</a>). Two of his 3 offspring, all asymptomatic, were found to have the same variant. <a href="#13" class="mim-tip-reference" title="Tang, N. L. S., Chow, C. C., Ko, G. T. C., Tai, M. H. L., Kwok, R., Yao, X. Q., Cockram, C. S. <strong>No mutation in the KCNE3 potassium channel gene in Chinese thyrotoxic hypokalaemic periodic paralysis patients.</strong> Clin. Endocr. 61: 109-112, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15212652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15212652</a>] [<a href="https://doi.org/10.1111/j.1365-2265.2004.02079.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15212652">Tang et al. (2004)</a> did not identify the R83H substitution, or any mutations in the KCNE3 gene, among 79 Chinese patients with thyrotoxic hypokalemic periodic paralysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12414843+15212652" 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="Jurkat-Rott, K., Lehmann-Horn, F. <strong>Genotype-phenotype correlation and therapeutic rationale in hyperkalemic periodic paralysis.</strong> Neurotherapeutics 4: 216-224, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17395131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17395131</a>] [<a href="https://doi.org/10.1016/j.nurt.2007.02.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17395131">Jurkat-Rott and Lehmann-Horn (2007)</a> again refuted the pathogenicity of the R83H variant, noting that it had been identified in 1.17% of patients and 1.16% of healthy controls, which does not support disease causality. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17395131" 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 BRUGADA SYNDROME 6 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KCNE3, ARG99HIS
|
|
</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> rs121908441 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908441;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/rs121908441?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=rs121908441" 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=rs121908441" 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=RCV000005880 OR RCV000170965 OR RCV000171754 OR RCV000618438" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005880, RCV000170965, RCV000171754, RCV000618438" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005880...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Brugada Syndrome</p><p>In 4 affected members of a Danish family with Brugada syndrome (<a href="/entry/613119">613119</a>), <a href="#4" class="mim-tip-reference" title="Delpon, E., Cordeiro, J. M., Nunez, L., Thomsen, P. E. B., Guerchicoff, A., Pollevick, G. D., Wu, Y., Kanters, J. K., Larsen, C. T., Hofman-Bang, J., Burashnikov, E., Christiansen, M., Antzelevitch, C. <strong>Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome.</strong> Circ. Arrhythm. Electrophysiol. 1: 209-218, 2008. Note: Erratum: Circ. Arrhythm. Electrophysiol. 1: e2, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19122847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19122847</a>] [<a href="https://doi.org/10.1161/CIRCEP.107.748103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19122847">Delpon et al. (2008)</a> identified heterozygosity for a G-to-A transition in the KCNE3 gene, predicted to result in an arg99-to-his (R99H) substitution. The mutation was not found in 3 unaffected family members, in 200 Danish control alleles, or in an additional 206 alleles of Caucasian European controls. In whole-cell patch-clamp studies, cotransfection of R99H-mutant KCNE3 with KCND3 (<a href="/entry/605411">605411</a>) resulted in a significant increase in transient outward current intensity compared to wildtype; the gain of function demonstrated a positive dominant effect, since the increase in current was comparable with or without the presence of wildtype KCNE3. Using tissues isolated from the left atrial appendages of human hearts, coimmunoprecipitation of Kv4.3 and KCNE3 was demonstrated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19122847" 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>Acquired Long QT Syndrome, Susceptibility to (1 patient)</p><p>In a 76-year-old Japanese woman with repeated episodes of paroxysmal atrial fibrillation (see <a href="/entry/608583">608583</a>), who developed torsade de pointes with a prolonged QT interval (see <a href="/entry/192500">192500</a>) after taking the drug disopyramide but was negative for mutation in 5 known LQT genes, <a href="#10" class="mim-tip-reference" title="Ohno, S., Toyoda, F., Zankov, D. P., Yoshida, H., Makiyama, T., Tsuji, K., Honda, T., Obayashi, K., Ueyama, H., Shimizu, W., Miyamoto, Y., Kamakura, S., Matsuura, H., Kita, T., Horie, M. <strong>Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome.</strong> Hum. Mutat. 30: 557-563, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19306396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19306396</a>] [<a href="https://doi.org/10.1002/humu.20834" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19306396">Ohno et al. (2009)</a> identified heterozygosity for the R99H mutation in KCNE3. There was no family history of sudden cardiac death or LQT, and family members declined to participate in the study. The mutation was not found in 200 healthy Japanese individuals from the general population. Electrophysiologic analysis demonstrated that the R99H mutant significantly reduced outward current compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19306396" 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 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KCNE3, THR4ALA
|
|
</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> rs200856070 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200856070;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/rs200856070?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=rs200856070" 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=rs200856070" 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=RCV000114366 OR RCV000455941 OR RCV000490275 OR RCV000621765 OR RCV000988596" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000114366, RCV000455941, RCV000490275, RCV000621765, RCV000988596" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000114366...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>The variant is classified as a variant of unknown significance because its contribution to a cardiac phenotype has not been confirmed.</p><p>In a 16-year-old Japanese boy with prolonged QT interval (see <a href="/entry/192500">192500</a>) discovered on a routine annual health examination, who had no history of faintness or syncope, <a href="#10" class="mim-tip-reference" title="Ohno, S., Toyoda, F., Zankov, D. P., Yoshida, H., Makiyama, T., Tsuji, K., Honda, T., Obayashi, K., Ueyama, H., Shimizu, W., Miyamoto, Y., Kamakura, S., Matsuura, H., Kita, T., Horie, M. <strong>Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome.</strong> Hum. Mutat. 30: 557-563, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19306396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19306396</a>] [<a href="https://doi.org/10.1002/humu.20834" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19306396">Ohno et al. (2009)</a> identified heterozygosity for a c.10A-G transition in the KCNE3 gene, resulting in a thr4-to-ala (T4A) substitution. The patient's resting ECG showed bradycardia for age (48 bpm) and QT prolongation (QTc = 525 ms). He was also found to carry a variant in the KCNH2 gene (G572S) known to be associated with LQT2 (see <a href="/entry/613688">613688</a>). There was no family history of syncope or sudden death. His asymptomatic mother and sister, who both exhibited prolongation of QTc on ECG (520 ms and 560 ms), were also heterozygous for the same 2 variants. <a href="#10" class="mim-tip-reference" title="Ohno, S., Toyoda, F., Zankov, D. P., Yoshida, H., Makiyama, T., Tsuji, K., Honda, T., Obayashi, K., Ueyama, H., Shimizu, W., Miyamoto, Y., Kamakura, S., Matsuura, H., Kita, T., Horie, M. <strong>Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome.</strong> Hum. Mutat. 30: 557-563, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19306396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19306396</a>] [<a href="https://doi.org/10.1002/humu.20834" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19306396">Ohno et al. (2009)</a> also detected the T4A KCNE3 variant in a 68-year-old Japanese woman who experienced hypokalemia-induced torsade de pointes at age 60 years. Her asymptomatic daughter, who had borderline QTc prolongation on ECG, also carried the T4A variant. Electrophysiologic analysis showed that the T4A KCNE3 variant did not have a statistically significant effect on current density or deactivation kinetics. The KCNE3 T4A variant was not found in 200 healthy Japanese individuals from the general population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19306396" 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 55-year-old Japanese man with syncope and a Brugada-like pattern on his electrocardiogram (see <a href="/entry/613119">613119</a>), <a href="#9" class="mim-tip-reference" title="Nakajima, T., Wu, J., Kaneko, Y., Ashihara, T., Ohno, S., Irie, T., Ding, W.-G., Matsuura, H., Kurabayashi, M., Horie, M. <strong>KCNE3 T4A as the genetic basis of Brugada-pattern electrocardiogram.</strong> Circ. J. 76: 2763-2772, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22987075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22987075</a>] [<a href="https://doi.org/10.1253/circj.cj-12-0551" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22987075">Nakajima et al. (2012)</a> identified heterozygosity for the T4A mutation in the KCNE3 gene. Beginning in his fourth decade of life, the patient had several episodes of syncope under specific conditions, such as standing up after drinking alcohol. There was no family history of sudden cardiac death. ECG showed saddle-type ST segment elevation in the right precordial leads, with a QTc of 414 ms. After provocation with pilsicainide, a coved-type ST segment elevation appeared in the right precordial leads at the second intercostal space. Upon electrophysiologic assessment, nonsustained polymorphic ventricular tachycardia was induced, but not ventricular fibrillation. Head-up tilt test provoked hypotension and bradycardia, followed by syncope, and the patient was diagnosed as having neurally mediated (vasovagal) syncope (see <a href="/entry/609289">609289</a>). Functional analysis in CHO cells showed significantly increased peak current densities with the mutant compared to wildtype channels, but there was no effect on time to peak or inactivation kinetics. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22987075" 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="Abbott2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N.
|
|
<strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong>
|
|
Cell 104: 217-231, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11207363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11207363</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11207363" 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(01)00207-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Abbott2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Abbott, G. W., Butler, M. H., Goldstein, S. A. N.
|
|
<strong>Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis.</strong>
|
|
FASEB J. 20: 293-301, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16449802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16449802</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16449802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1096/fj.05-5070com" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Abbott1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Abbott, G. W., Sesti, F., Splawski, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N.
|
|
<strong>MiRP1 forms I(Kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong>
|
|
Cell 97: 175-187, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10219239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10219239</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10219239" 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)80728-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Delpon2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Delpon, E., Cordeiro, J. M., Nunez, L., Thomsen, P. E. B., Guerchicoff, A., Pollevick, G. D., Wu, Y., Kanters, J. K., Larsen, C. T., Hofman-Bang, J., Burashnikov, E., Christiansen, M., Antzelevitch, C.
|
|
<strong>Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome.</strong>
|
|
Circ. Arrhythm. Electrophysiol. 1: 209-218, 2008. Note: Erratum: Circ. Arrhythm. Electrophysiol. 1: e2, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19122847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19122847</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19122847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1161/CIRCEP.107.748103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Dias Da Silva2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dias Da Silva, M. R., Cerutti, J. M., Arnaldi, L. A. T., Maciel, R. M. B.
|
|
<strong>A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis.</strong>
|
|
J. Clin. Endocr. Metab. 87: 4881-4884, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12414843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12414843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12414843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2002-020698" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Jurkat-Rott2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jurkat-Rott, K., Lehmann-Horn, F.
|
|
<strong>Periodic paralysis mutation MiRP2-R83H in controls: interpretations and general recommendation.</strong>
|
|
Neurology 62: 1012-1015, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15037716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15037716</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15037716" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000119392.29624.88" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Jurkat-Rott2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jurkat-Rott, K., Lehmann-Horn, F.
|
|
<strong>Genotype-phenotype correlation and therapeutic rationale in hyperkalemic periodic paralysis.</strong>
|
|
Neurotherapeutics 4: 216-224, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17395131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17395131</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17395131" 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.nurt.2007.02.001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Melman2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Melman, Y. F., Um, S. Y., Krumerman, A., Kagan, A., McDonald, T. V.
|
|
<strong>KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity.</strong>
|
|
Neuron 42: 927-937, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15207237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15207237</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15207237" 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.2004.06.001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Nakajima2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nakajima, T., Wu, J., Kaneko, Y., Ashihara, T., Ohno, S., Irie, T., Ding, W.-G., Matsuura, H., Kurabayashi, M., Horie, M.
|
|
<strong>KCNE3 T4A as the genetic basis of Brugada-pattern electrocardiogram.</strong>
|
|
Circ. J. 76: 2763-2772, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22987075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22987075</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22987075" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1253/circj.cj-12-0551" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Ohno2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ohno, S., Toyoda, F., Zankov, D. P., Yoshida, H., Makiyama, T., Tsuji, K., Honda, T., Obayashi, K., Ueyama, H., Shimizu, W., Miyamoto, Y., Kamakura, S., Matsuura, H., Kita, T., Horie, M.
|
|
<strong>Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome.</strong>
|
|
Hum. Mutat. 30: 557-563, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19306396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19306396</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19306396" 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.20834" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Schroeder2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schroeder, B. C., Waldegger, S., Fehr, S., Bleich, M., Warth, R., Greger, R., Jentsch, T. J.
|
|
<strong>A constitutively open potassium channel formed by KCNQ1 and KCNE3.</strong>
|
|
Nature 403: 196-199, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10646604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10646604</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10646604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/35003200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Sternberg2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sternberg, D., Tabti, N., Fournier, E., Hainque, B., Fontaine, B.
|
|
<strong>Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis.</strong>
|
|
Neurology 61: 857-859, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14504341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14504341</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14504341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000082392.66713.e3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Tang2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tang, N. L. S., Chow, C. C., Ko, G. T. C., Tai, M. H. L., Kwok, R., Yao, X. Q., Cockram, C. S.
|
|
<strong>No mutation in the KCNE3 potassium channel gene in Chinese thyrotoxic hypokalaemic periodic paralysis patients.</strong>
|
|
Clin. Endocr. 61: 109-112, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15212652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15212652</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15212652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2265.2004.02079.x" 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">
|
|
Marla J. F. O'Neill - updated : 3/28/2014
|
|
</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 : 11/24/2009<br>Marla J. F. O'Neill - updated : 11/11/2009<br>Patricia A. Hartz - updated : 5/16/2005<br>Cassandra L. Kniffin - updated : 8/31/2004<br>John A. Phillips, III - updated : 4/8/2003<br>Stylianos E. Antonarakis - updated : 1/29/2001
|
|
</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">
|
|
Ada Hamosh : 1/14/2000
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 09/19/2018
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 03/29/2018<br>carol : 03/28/2018<br>joanna : 06/24/2016<br>carol : 4/2/2014<br>mcolton : 3/28/2014<br>carol : 12/15/2011<br>carol : 2/5/2010<br>ckniffin : 2/1/2010<br>ckniffin : 11/24/2009<br>wwang : 11/11/2009<br>terry : 11/11/2009<br>wwang : 5/20/2005<br>wwang : 5/16/2005<br>carol : 9/3/2004<br>ckniffin : 8/31/2004<br>tkritzer : 4/16/2003<br>carol : 4/15/2003<br>tkritzer : 4/15/2003<br>terry : 4/8/2003<br>ckniffin : 2/5/2003<br>mgross : 1/30/2001<br>mgross : 1/29/2001<br>mgross : 1/29/2001<br>alopez : 1/14/2000
|
|
</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> 604433
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
POTASSIUM CHANNEL, VOLTAGE-GATED, ISK-RELATED SUBFAMILY, MEMBER 3; KCNE3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
MINIMUM POTASSIUM ION CHANNEL-RELATED PEPTIDE 2; MIRP2<br />
|
|
MINK-RELATED PEPTIDE 2
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: KCNE3</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 11q13.4
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 11:74,454,841-74,467,549 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
11q13.4
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Brugada syndrome 6
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613119
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Abbott et al. (1999) cloned the potassium channel beta subunit KCNE3 by homology to KCNE1 (176261). KCNE3 is a 103-amino acid protein with a relative molecular mass of about 12 kD that displays roughly 35% identity to other KCNE proteins within the single transmembrane domain and a following short stretch. Northern blot analysis revealed a prominent band in the kidney, moderate expression in the small intestine, and weaker bands in most other tissues, including colon and heart. By Northern blot analysis, Abbott et al. (2001) detected KCNE3 mRNA in skeletal muscle, but not in small intestine, colon, kidney, or liver. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By radiation hybrid analysis, Abbott et al. (2001) mapped the KCNE3 gene to chromosome 11q13-q14. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>When KCNQ1 (607542) interacts with the beta subunit KCNE1, a slow depolarization-activated potassium current I(Ks) is formed that is affected in some forms of cardiac arrhythmia. Schroeder et al. (2000) demonstrated that the beta subunit KCNE3 markedly changes KCNQ1 properties to yield currents that are nearly instantaneous and depend linearly on voltage. KCNE3 also suppresses the currents of KCNQ4 (603537) and HERG (see 152427) potassium channels. In the intestine, KCNQ1 and KCNE3 mRNAs colocalized in crypt cells. This localization, and the pharmacology, voltage dependence, and stimulation by cyclic AMP of KCNQ1/KCNE3 currents, indicated that these proteins may assemble to form the potassium channel that is important for cyclic AMP-stimulated intestinal chloride secretion and that is involved in secretory diarrhea and cystic fibrosis. </p><p>In skeletal muscle cells, Abbott et al. (2001) demonstrated that KCNE3 forms stable complexes with the pore-forming unit Kv3.4 (KCNC4; 176265), resulting in potassium channels with increased conductance, faster recovery from inactivation, and slower cumulative inactivation. KCNE3-KCNE4 channels are 80-fold more active at -40 mv and establish the resting membrane potential of skeletal muscle cells. Western blot analysis detected the KCNE3 protein in skeletal muscle plasma membranes. </p><p>Melman et al. (2004) showed that KCNE1 and KCNE3 associate with an extended binding interface of KCNQ1 that includes structures within the channel pore and C terminus. </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>Brugada Syndrome 6</em></strong></p><p>
|
|
Delpon et al. (2008) sequentially screened 14 ion channel genes in 105 probands with Brugada syndrome (see 601144) and identified a heterozygous mutation in the KCNE3 gene (R99H; 604433.0002) in a proband from a Danish pedigree (Brugada syndrome-6; BRGDA6, 613119). Cotransfection of R99H-mutant KCNE3 with KCNQ1 (607542) produced no alteration in tail current magnitude or kinetics, whereas cotransfection of R99H-mutant KCNE3 with KCND3 (605411) resulted in a significant increase in the transient outward current intensity compared to wildtype. The authors also demonstrated coimmunoprecipitation of Kv4.3 and KCNE3 in human left atrial appendage tissue. </p><p>In 40 consecutive Japanese patients with a Brugada-like pattern on electrocardiography, Nakajima et al. (2012) analyzed all coding exons of the SCN5A (600163), SCN1B (600235), SCN3B (608214), KCNE5 (300328), and KCNE3 genes, and identified a 55-year-old man who was heterozygous for a T4A mutation in KCNE3 (604433.0003) and negative for mutation in the other 4 genes as well as in the CACNA1C (114205) and CACNB2 (600003) genes. Functional analysis demonstrated a significantly increased current density with the T4A mutant compared to wildtype. </p><p><strong><em>Possible Role in Periodic Paralysis</em></strong></p><p>
|
|
Although Abbott et al. (2001) identified an arg83-to-his (R83H; 604433.0001) substitution in 2 of 100 patients with hyperkalemic periodic paralysis (HYPP; 170500) and hypokalemic periodic paralysis (HOKPP; 170400), respectively, Sternberg et al. (2003) and Jurkat-Rott and Lehmann-Horn (2004) concluded that the R83H variant does not play a causative role in periodic paralysis. See 604433.0001 for detailed discussion. </p><p>Dias Da Silva et al. (2002) identified the R83H variant in a sporadic case of thyrotoxic periodic paralysis (TPP; 188580). The patient was a 44-year-old Caucasian man of Portuguese descent who had experienced episodic paralysis for 2 years before developing signs of thyrotoxicosis caused by Graves disease (275000). Tang et al. (2004) did not identify the R83H substitution, or any mutations in the KCNE3 gene, among 79 Chinese patients with thyrotoxic hypokalemic periodic paralysis. </p><p><strong><em>Possible Role in Acquired Long QT Syndrome</em></strong></p><p>
|
|
In 485 Japanese probands with congenital or acquired long QT syndrome (see LQT1, 192500), who on electrocardiography exhibited QT interval prolongation of 460 ms or more or who had documented torsade de pointes, Ohno et al. (2009) analyzed 5 known LQT genes (KCNQ1, 607542; KCNH2, 152427; SCN5A, 600163; KCNE1, 176261; and KCNE2, 603796) as well as the candidate gene KCNE3. A 76-year-old woman with acquired LQT who was negative for mutation in the 5 known LQT genes was found to be heterozygous for the R99H missense mutation in KCNE3 (604433.0002), previously associated with Brugada syndrome. In another 2 unrelated probands with LQT, Ohno et al. (2009) identified a different missense mutation in KCNE3 (T4A; 604433.0003); however, in 1 family, the proband and his asymptomatic mother and sister were also heterozygous for a known LQT-associated variant in the KCNH2 gene (G572S), and electrophysiologic analysis showed that the KCNE3 T4A variant did not have a statistically significant effect on current density. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>3 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNE3, ARG83HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs17215437,
|
|
|
|
|
|
gnomAD: rs17215437,
|
|
|
|
|
|
ClinVar: RCV000005879, RCV000171813, RCV000223897, RCV000253742, RCV000415218, RCV000538199, RCV000852657, RCV000988595
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled HYPOKALEMIC PERIODIC PARALYSIS, HYPERKALEMIC PERIODIC PARALYSIS, and SUSCEPTIBILITY TO THYROTOXIC PERIODIC PARALYSIS based on the findings of Abbott et al. (2001) and Dias Da Silva et al. (2002), has been reclassified based on the findings of Sternberg et al. (2003) and Jurkat-Rott and Lehmann-Horn (2004). </p><p>Abbott et al. (2001) identified a 340G-A transition in the KCNE3 gene, resulting in an arg83-to-his (R83H) substitution in 2 of 100 patients with atypical forms of hyperkalemic periodic paralysis (HYPP; 170500) and hypokalemic periodic paralysis (HOKPP; 170400), respectively. However, Sternberg et al. (2003) and Jurkat-Rott and Lehmann-Horn (2004) concluded that the R83H variant does not play a causative role in periodic paralysis and that it is a polymorphism. </p><p>Abbott et al. (2001) reported a male proband with atypical HYPP who was negative for mutations in the SCN4A gene and who carried the R83H variant. He presented at 22 months of age with episodic weakness of the extremities. Most episodes came on during sleep and were brief (12 hours), although they occasionally lasted for days. Serum potassium levels during attacks were normal. High carbohydrate meals helped resolve attacks, and treatment with a carbonic anhydrase inhibitor prevented attacks. The age at onset, frequent nature of attacks, and improvement with carbohydrate loading were all consistent with HYPP; however, provocative testing with potassium had not been performed. Frequent attacks upon awakening and absence of myotonia were considered atypical for this diagnosis. Abbott et al. (2001) reported a male proband with atypical HOKPP who was negative for mutations in the SCN4A and CACNA1S genes and who carried the R83H variant. He had onset of episodic paralytic weakness at the age of 14 years. Episodes were characterized by weakness primarily affecting the lower extremities and lasting hours to days, and were usually precipitated by strenuous exercise followed by rest or after prolonged sitting. Carbohydrate ingestion did not precipitate attacks, alcohol intake appeared to facilitate recovery from an attack, and potassium had no effect. He was classified as having hypokalemic periodic paralysis because of the typical age of onset, paralytic attacks that most often occurred after exercise, a low potassium level during a spontaneous attack, and the ability to precipitate an attack with insulin and glucose on 1 occasion. Atypical for this diagnosis was that a second provocative test was negative and that attacks usually occurred while awake. The variant was not found in DNA from a control population of 120 unaffected individuals, suggesting to them that it does not represent a polymorphism. </p><p>Abbott et al. (2001) reported functional expression studies that showed that the mutant R83H KCNE3-Kv3.4 complexes exhibited reduced current density and diminished capacity to set resting membrane potential as a dominant-negative effect compared to wildtype. In in vitro studies, Abbott et al. (2006) found that the R83H variant shifts the voltage-dependence of channel activation in response to pH change. The current through the mutant channel decreased compared to wildtype as intracellular pH was lowered. The authors suggested that R83H acts as a regulatory domain, and concluded that the variation may predispose to the development of periodic paralysis. </p><p>In contrast, Sternberg et al. (2003) did not identify the R83H mutation in 64 probands with either HYPP or HOKPP in whom mutations in the SCN4A and CACNA1S genes had been excluded. One patient with HOKPP had the R83H change, but he also had a mutation in the SCN4A gene (R672H; 603967.0016). His father, who had the same clinical phenotype and the SCN4A mutation, did not carry the R83H mutation, whereas the asymptomatic mother carried the R83H variant. The findings yielded a frequency of 0.0096 in patients with periodic paralysis (1 in 104) and 0.0158 (8 of 506) in healthy controls. Likewise, Jurkat-Rott and Lehmann-Horn (2004) identified the R83H mutation in 1 of 76 patients with HYPP, in 1 of 61 patients with paramyotonia congenita (608390), in 5 unaffected relatives, in 0 of 8 patients with TTPP, and in 3 of 321 healthy controls, suggesting that it is a polymorphism. Provocation of an unaffected carrier with glucose or potassium administration did not induce weakness. The authors offered a formula for determining causality of a mutation based on reduced penetrance, but concluded that the R83H mutation does not cause these muscle disorders. </p><p>Dias Da Silva et al. (2002) identified the R83H substitution in 1 of 15 patients with thyrotoxic hypokalemic periodic paralysis (188580). The patient was a 44-year-old Caucasian man of Portuguese descent who experienced episodic paralysis for 2 years before developing thyrotoxicosis caused by Graves disease (275000). Two of his 3 offspring, all asymptomatic, were found to have the same variant. Tang et al. (2004) did not identify the R83H substitution, or any mutations in the KCNE3 gene, among 79 Chinese patients with thyrotoxic hypokalemic periodic paralysis. </p><p>Jurkat-Rott and Lehmann-Horn (2007) again refuted the pathogenicity of the R83H variant, noting that it had been identified in 1.17% of patients and 1.16% of healthy controls, which does not support disease causality. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 BRUGADA SYNDROME 6 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNE3, ARG99HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908441,
|
|
|
|
|
|
gnomAD: rs121908441,
|
|
|
|
|
|
ClinVar: RCV000005880, RCV000170965, RCV000171754, RCV000618438
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Brugada Syndrome</p><p>In 4 affected members of a Danish family with Brugada syndrome (613119), Delpon et al. (2008) identified heterozygosity for a G-to-A transition in the KCNE3 gene, predicted to result in an arg99-to-his (R99H) substitution. The mutation was not found in 3 unaffected family members, in 200 Danish control alleles, or in an additional 206 alleles of Caucasian European controls. In whole-cell patch-clamp studies, cotransfection of R99H-mutant KCNE3 with KCND3 (605411) resulted in a significant increase in transient outward current intensity compared to wildtype; the gain of function demonstrated a positive dominant effect, since the increase in current was comparable with or without the presence of wildtype KCNE3. Using tissues isolated from the left atrial appendages of human hearts, coimmunoprecipitation of Kv4.3 and KCNE3 was demonstrated. </p><p>Acquired Long QT Syndrome, Susceptibility to (1 patient)</p><p>In a 76-year-old Japanese woman with repeated episodes of paroxysmal atrial fibrillation (see 608583), who developed torsade de pointes with a prolonged QT interval (see 192500) after taking the drug disopyramide but was negative for mutation in 5 known LQT genes, Ohno et al. (2009) identified heterozygosity for the R99H mutation in KCNE3. There was no family history of sudden cardiac death or LQT, and family members declined to participate in the study. The mutation was not found in 200 healthy Japanese individuals from the general population. Electrophysiologic analysis demonstrated that the R99H mutant significantly reduced outward current compared to wildtype. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNE3, THR4ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs200856070,
|
|
|
|
|
|
gnomAD: rs200856070,
|
|
|
|
|
|
ClinVar: RCV000114366, RCV000455941, RCV000490275, RCV000621765, RCV000988596
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>The variant is classified as a variant of unknown significance because its contribution to a cardiac phenotype has not been confirmed.</p><p>In a 16-year-old Japanese boy with prolonged QT interval (see 192500) discovered on a routine annual health examination, who had no history of faintness or syncope, Ohno et al. (2009) identified heterozygosity for a c.10A-G transition in the KCNE3 gene, resulting in a thr4-to-ala (T4A) substitution. The patient's resting ECG showed bradycardia for age (48 bpm) and QT prolongation (QTc = 525 ms). He was also found to carry a variant in the KCNH2 gene (G572S) known to be associated with LQT2 (see 613688). There was no family history of syncope or sudden death. His asymptomatic mother and sister, who both exhibited prolongation of QTc on ECG (520 ms and 560 ms), were also heterozygous for the same 2 variants. Ohno et al. (2009) also detected the T4A KCNE3 variant in a 68-year-old Japanese woman who experienced hypokalemia-induced torsade de pointes at age 60 years. Her asymptomatic daughter, who had borderline QTc prolongation on ECG, also carried the T4A variant. Electrophysiologic analysis showed that the T4A KCNE3 variant did not have a statistically significant effect on current density or deactivation kinetics. The KCNE3 T4A variant was not found in 200 healthy Japanese individuals from the general population. </p><p>In a 55-year-old Japanese man with syncope and a Brugada-like pattern on his electrocardiogram (see 613119), Nakajima et al. (2012) identified heterozygosity for the T4A mutation in the KCNE3 gene. Beginning in his fourth decade of life, the patient had several episodes of syncope under specific conditions, such as standing up after drinking alcohol. There was no family history of sudden cardiac death. ECG showed saddle-type ST segment elevation in the right precordial leads, with a QTc of 414 ms. After provocation with pilsicainide, a coved-type ST segment elevation appeared in the right precordial leads at the second intercostal space. Upon electrophysiologic assessment, nonsustained polymorphic ventricular tachycardia was induced, but not ventricular fibrillation. Head-up tilt test provoked hypotension and bradycardia, followed by syncope, and the patient was diagnosed as having neurally mediated (vasovagal) syncope (see 609289). Functional analysis in CHO cells showed significantly increased peak current densities with the mutant compared to wildtype channels, but there was no effect on time to peak or inactivation kinetics. </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">
|
|
Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., Goldstein, S. A. N.
|
|
<strong>MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.</strong>
|
|
Cell 104: 217-231, 2001.
|
|
|
|
|
|
[PubMed: 11207363]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(01)00207-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Abbott, G. W., Butler, M. H., Goldstein, S. A. N.
|
|
<strong>Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis.</strong>
|
|
FASEB J. 20: 293-301, 2006.
|
|
|
|
|
|
[PubMed: 16449802]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1096/fj.05-5070com]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Abbott, G. W., Sesti, F., Splawski, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N.
|
|
<strong>MiRP1 forms I(Kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong>
|
|
Cell 97: 175-187, 1999.
|
|
|
|
|
|
[PubMed: 10219239]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)80728-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Delpon, E., Cordeiro, J. M., Nunez, L., Thomsen, P. E. B., Guerchicoff, A., Pollevick, G. D., Wu, Y., Kanters, J. K., Larsen, C. T., Hofman-Bang, J., Burashnikov, E., Christiansen, M., Antzelevitch, C.
|
|
<strong>Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome.</strong>
|
|
Circ. Arrhythm. Electrophysiol. 1: 209-218, 2008. Note: Erratum: Circ. Arrhythm. Electrophysiol. 1: e2, 2008.
|
|
|
|
|
|
[PubMed: 19122847]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1161/CIRCEP.107.748103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dias Da Silva, M. R., Cerutti, J. M., Arnaldi, L. A. T., Maciel, R. M. B.
|
|
<strong>A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis.</strong>
|
|
J. Clin. Endocr. Metab. 87: 4881-4884, 2002.
|
|
|
|
|
|
[PubMed: 12414843]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-020698]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jurkat-Rott, K., Lehmann-Horn, F.
|
|
<strong>Periodic paralysis mutation MiRP2-R83H in controls: interpretations and general recommendation.</strong>
|
|
Neurology 62: 1012-1015, 2004.
|
|
|
|
|
|
[PubMed: 15037716]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000119392.29624.88]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jurkat-Rott, K., Lehmann-Horn, F.
|
|
<strong>Genotype-phenotype correlation and therapeutic rationale in hyperkalemic periodic paralysis.</strong>
|
|
Neurotherapeutics 4: 216-224, 2007.
|
|
|
|
|
|
[PubMed: 17395131]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nurt.2007.02.001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Melman, Y. F., Um, S. Y., Krumerman, A., Kagan, A., McDonald, T. V.
|
|
<strong>KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity.</strong>
|
|
Neuron 42: 927-937, 2004.
|
|
|
|
|
|
[PubMed: 15207237]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neuron.2004.06.001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakajima, T., Wu, J., Kaneko, Y., Ashihara, T., Ohno, S., Irie, T., Ding, W.-G., Matsuura, H., Kurabayashi, M., Horie, M.
|
|
<strong>KCNE3 T4A as the genetic basis of Brugada-pattern electrocardiogram.</strong>
|
|
Circ. J. 76: 2763-2772, 2012.
|
|
|
|
|
|
[PubMed: 22987075]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1253/circj.cj-12-0551]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ohno, S., Toyoda, F., Zankov, D. P., Yoshida, H., Makiyama, T., Tsuji, K., Honda, T., Obayashi, K., Ueyama, H., Shimizu, W., Miyamoto, Y., Kamakura, S., Matsuura, H., Kita, T., Horie, M.
|
|
<strong>Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome.</strong>
|
|
Hum. Mutat. 30: 557-563, 2009.
|
|
|
|
|
|
[PubMed: 19306396]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20834]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schroeder, B. C., Waldegger, S., Fehr, S., Bleich, M., Warth, R., Greger, R., Jentsch, T. J.
|
|
<strong>A constitutively open potassium channel formed by KCNQ1 and KCNE3.</strong>
|
|
Nature 403: 196-199, 2000.
|
|
|
|
|
|
[PubMed: 10646604]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/35003200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sternberg, D., Tabti, N., Fournier, E., Hainque, B., Fontaine, B.
|
|
<strong>Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis.</strong>
|
|
Neurology 61: 857-859, 2003.
|
|
|
|
|
|
[PubMed: 14504341]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000082392.66713.e3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tang, N. L. S., Chow, C. C., Ko, G. T. C., Tai, M. H. L., Kwok, R., Yao, X. Q., Cockram, C. S.
|
|
<strong>No mutation in the KCNE3 potassium channel gene in Chinese thyrotoxic hypokalaemic periodic paralysis patients.</strong>
|
|
Clin. Endocr. 61: 109-112, 2004.
|
|
|
|
|
|
[PubMed: 15212652]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2265.2004.02079.x]
|
|
|
|
|
|
</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">
|
|
Marla J. F. O'Neill - updated : 3/28/2014<br>Cassandra L. Kniffin - updated : 11/24/2009<br>Marla J. F. O'Neill - updated : 11/11/2009<br>Patricia A. Hartz - updated : 5/16/2005<br>Cassandra L. Kniffin - updated : 8/31/2004<br>John A. Phillips, III - updated : 4/8/2003<br>Stylianos E. Antonarakis - updated : 1/29/2001
|
|
</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">
|
|
Ada Hamosh : 1/14/2000
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 09/19/2018<br>carol : 03/29/2018<br>carol : 03/28/2018<br>joanna : 06/24/2016<br>carol : 4/2/2014<br>mcolton : 3/28/2014<br>carol : 12/15/2011<br>carol : 2/5/2010<br>ckniffin : 2/1/2010<br>ckniffin : 11/24/2009<br>wwang : 11/11/2009<br>terry : 11/11/2009<br>wwang : 5/20/2005<br>wwang : 5/16/2005<br>carol : 9/3/2004<br>ckniffin : 8/31/2004<br>tkritzer : 4/16/2003<br>carol : 4/15/2003<br>tkritzer : 4/15/2003<br>terry : 4/8/2003<br>ckniffin : 2/5/2003<br>mgross : 1/30/2001<br>mgross : 1/29/2001<br>mgross : 1/29/2001<br>alopez : 1/14/2000
|
|
</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>
|
|
|
|
|