4459 lines
352 KiB
Text
4459 lines
352 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
|
|
|
|
- *300036 - SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, CREATINE), MEMBER 8; SLC6A8
|
|
|
|
|
|
- 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=300036"><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 class="hidden-sm hidden-xs">
|
|
|
|
|
|
Display:
|
|
|
|
|
|
<label style="font-weight: normal"><input type="checkbox" id="mimToggleChangeBars" checked /> Change Bars </label>
|
|
|
|
|
|
</span>
|
|
|
|
|
|
</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">*300036</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/300036">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=ENSG00000130821;t=ENST00000253122" 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=6535" 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=300036" 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=ENSG00000130821;t=ENST00000253122" 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_001142805,NM_001142806,NM_005629" 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_005629" 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=300036" 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=02073&isoform_id=02073_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/SLC6A8" 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/493132,602434,765234,1020319,1352529,1628387,5032097,15214460,51859060,62088988,119593233,119593236,119593238,167540808,194380524,218563756,218563758,346722568,580961620,608785491,608785493,608785495,608785497,2194521884" 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/P48029" 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=6535" 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=ENSG00000130821;t=ENST00000253122" 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=SLC6A8" 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=SLC6A8" 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+6535" 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/SLC6A8" 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:6535" 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/6535" 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=chrX&hgg_gene=ENST00000253122.10&hgg_start=153687926&hgg_end=153696593&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:11055" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:11055" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/slc6a8" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=300036[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=300036[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/SLC6A8/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000130821" 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=SLC6A8" 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=SLC6A8" 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=SLC6A8" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.LOVD.nl/SLC6A8" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SLC6A8&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/PA35915" 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:11055" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0031935.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:2147834" 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/SLC6A8#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:2147834" 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/6535/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=6535" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-071024-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:300036" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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://reactome.org/content/query?q=SLC6A8&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 698290008<br />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
300036
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, CREATINE), MEMBER 8; SLC6A8
|
|
|
|
</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">
|
|
CREATINE TRANSPORTER; CT1; CRTR; CRT
|
|
</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=SLC6A8" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SLC6A8</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/X/834?start=-3&limit=10&highlight=834">Xq28</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:153687926-153696593&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'})">X:153,687,926-153,696,593</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/X/834?start=-3&limit=10&highlight=834">
|
|
Xq28
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cerebral creatine deficiency syndrome 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300352"> 300352 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/300036" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/300036" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The creatine-phosphocreatine shuttle has important functions in the temporal and spatial maintenance of the energy supply to skeletal and cardiac muscle. Muscle cells do not synthesize creatine, but take it up via a special sodium-dependent transporter, the creatine transporter (SLC6A8). Thus, SLC6A8 has an important role in muscle physiology, and inhibition of creatine transport in experimental animals causes muscle weakness (<a href="#8" class="mim-tip-reference" title="Gregor, P., Nash, S. R., Caron, M. G., Seldin, M. F., Warren, S. T. <strong>Assignment of the creatine transporter gene (SLC6A8) to human chromosome Xq28 telomeric to G6PD.</strong> Genomics 25: 332-333, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7774949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7774949</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80155-f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7774949">Gregor et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7774949" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Using rat Crt1 to probe a human hippocampus cDNA library, <a href="#2" class="mim-tip-reference" title="Barnwell, L. F. S., Chaudhuri, G., Townsel, J. G. <strong>Cloning and sequencing of a cDNA encoding a novel member of the human brain GABA/noradrenaline neurotransmitter transporter family.</strong> Gene 159: 287-288, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7622069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7622069</a>] [<a href="https://doi.org/10.1016/0378-1119(95)00104-e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7622069">Barnwell et al. (1995)</a> obtained 2 groups of CRT clones, which they called CRT1 and CRT2. CRT1 is homologous to rat Crt1. CRT2 encodes a deduced 732-amino acid protein with a unique N-terminal segment and 3 short insertions in its C-terminal half that are not found in CRT1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7622069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Dai, W., Vinnakota, S., Qian, X., Kunze, D. L., Sarkar, H. K. <strong>Molecular characterization of the human CRT-1 creatine transporter expressed in Xenopus oocytes.</strong> Arch. Biochem. Biophys. 361: 75-84, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9882430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9882430</a>] [<a href="https://doi.org/10.1006/abbi.1998.0959" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9882430">Dai et al. (1999)</a> obtained a CRT1 clone from a human heart cDNA library. The deduced protein contains pro285 (P285) rather than ala285 (A285), which was predicted from a CRT1 clone obtained from a human kidney cDNA library by <a href="#17" class="mim-tip-reference" title="Nash, S. R., Giros, B., Kingsmore, S. F., Rochelle, J. M., Suter, S. T., Gregor, P., Seldin, M. F., Caron, M. G. <strong>Cloning, pharmacological characterization, and genomic localization of the human creatine transporter.</strong> Receptors Channels 2: 165-174, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7953292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7953292</a>]" pmid="7953292">Nash et al. (1994)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9882430+7953292" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using Western blot analysis, <a href="#18" class="mim-tip-reference" title="Peral, M. J., Garcia-Delgado, M., Calonge, M. L., Duran, J. M., De La Horra, M. C., Wallimann, T., Speer, O., Ilundain, A. A. <strong>Human, rat and chicken small intestinal Na(+)-Cl(-)-creatine transporter: functional, molecular characterization and localization.</strong> J. Physiol. 545: 133-144, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12433955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12433955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12433955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1113/jphysiol.2002.026377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12433955">Peral et al. (2002)</a> detected robust expression of an apparent 57-kD CRT protein in human brush border cells. Weaker expression of CRT proteins with apparent molecular masses of 72 and 52 kD was detected in human heart. Immunofluorescence analysis of human ileum detected specific staining at apical membranes of cells lining the villus. In situ hybridization of chicken small intestine showed Crt expression restricted to cells lining the villus, with no Crt expression in crypt cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12433955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using RT-PCR analysis, <a href="#1" class="mim-tip-reference" title="Abplanalp, J., Laczko, E., Philp, N. J., Neidhardt, J., Zuercher, J., Braun, P., Schorderet, D. F., Munier, F. L., Verrey, F., Berger, W., Camargo, S. M. R., Kloeckener-Gruissem, B. <strong>The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter.</strong> Hum. Molec. Genet. 22: 3218-3226, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23578822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23578822</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23578822[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddt175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23578822">Abplanalp et al. (2013)</a> detected robust SLC6A8 expression in human kidney, retina, brain, heart, and muscle, with weaker expression in lens. In contrast, SLC16A12 (<a href="/entry/611910">611910</a>), another creatine transporter, was highly expressed in kidney and retina only, with weaker expression in other tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23578822" 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>By assaying Xenopus oocytes injected with cRNAs, <a href="#6" class="mim-tip-reference" title="Dai, W., Vinnakota, S., Qian, X., Kunze, D. L., Sarkar, H. K. <strong>Molecular characterization of the human CRT-1 creatine transporter expressed in Xenopus oocytes.</strong> Arch. Biochem. Biophys. 361: 75-84, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9882430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9882430</a>] [<a href="https://doi.org/10.1006/abbi.1998.0959" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9882430">Dai et al. (1999)</a> found that human CRT1 induced saturable Na(+)- and Cl(-)-dependent creatine uptake. CRT1 forms with P285 were as efficient in creatine uptake as those with A285. However, the P285 form had higher sensitivity to guanidinoethane sulfonic acid, a potent inhibitor of taurine transport, than the A285 form. The substitution did not alter CRT1 sensitivity to other inhibitors tested. Kinetic analysis revealed that 2 Na+ and 1 Cl- were required for electrogenic transport of 1 creatine molecule. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9882430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using Western blot analysis and confocal immunohistochemistry, <a href="#23" class="mim-tip-reference" title="Schlattner, U., Mockli, N., Speer, O., Werner, S., Wallimann, T. <strong>Creatine kinase and creatine transporter in normal, wounded, and diseased skin.</strong> J. Invest. Derm. 118: 416-423, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11874479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11874479</a>] [<a href="https://doi.org/10.1046/j.0022-202x.2001.01697.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11874479">Schlattner et al. (2002)</a> investigated the localization of creatine kinases (CKs) in mouse and human skin under healthy and pathologic conditions. In mouse skin, they found high amounts of cytosolic brain CK (CKB; <a href="/entry/123280">123280</a>) coexpressed with lower amounts of ubiquitous mitochondrial CK (CKMT1B; <a href="/entry/123290">123290</a>), both mainly localized in suprabasal layers of the dermis, different cell types of hair follicles, sebaceous glands, and the subcutaneous panniculus carnosus muscle. Except for sebaceous glands, these cells also expressed CRT. Western blot analysis showed that Ckb and Crt were upregulated about 3-fold immediately after wounding of mouse skin, whereas the amount of Ckmt1b increased 10 to 15 days after wounding. Healthy and psoriatic human skin showed a similar coexpression pattern of CKB, CKMT1B, and CRT, with CRT upregulated in psoriasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11874479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Shojaiefard, M., Christie, D. L., Lang, F. <strong>Stimulation of the creatine kinase transporter SLC6A8 by the protein kinases SGK1 and SGK3.</strong> Biochem. Biophys. Res. Commun. 334: 742-746, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16036218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16036218</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.06.164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16036218">Shojaiefard et al. (2005)</a> showed that human SGK1 (<a href="/entry/602958">602958</a>) or SGK3 (<a href="/entry/607591">607591</a>) stimulated creatine-induced currents in Xenopus oocytes heterologously expressing human SLC6A8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16036218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Ji, L., Zhao, X., Zhang, B., Kang, L., Song, W., Zhao, B., Xie, W., Chen, L., Hu, X. <strong>Slc6a8-mediated creatine uptake and accumulation reprogram macrophage polarization via regulating cytokine responses.</strong> Immunity 51: 272-284, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31399282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31399282</a>] [<a href="https://doi.org/10.1016/j.immuni.2019.06.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31399282">Ji et al. (2019)</a> found that mouse macrophages maintained high intracellular creatine through Slc6a8-mediated uptake and that macrophage polarization was coupled with changes in creatine uptake. Creatine was dispensable for macrophage development and functionality in steady state, but it inhibited polarization of Ifn-gamma (IFNG; <a href="/entry/147570">147570</a>)-activated macrophages by suppressing JAK (see <a href="/entry/147795">147795</a>)-Stat1 (<a href="/entry/600555">600555</a>) signaling and Stat1 target gene activation. Consequently, creatine depletion promoted polarization of Ifn-gamma activated macrophages and enhanced host defense against infection by Listeria monocytogenes. Creatine supported polarization of Il4 (<a href="/entry/147780">147780</a>)-activated macrophages by promoting expression of arginase-1 (ARG1; <a href="/entry/608313">608313</a>) through ATP-dependent SWI/SNF (see <a href="/entry/600014">600014</a>)-mediated chromatin remodeling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31399282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#21" class="mim-tip-reference" title="Sandoval, N., Bauer, D., Brenner, V., Coy, J. F., Drescher, B., Kioschis, P., Korn, B., Nyakatura, G., Poustka, A., Reichwald, K., Rosenthal, A., Platzer, M. <strong>The genomic organization of a human creatine transporter (CRTR) gene located in Xq28.</strong> Genomics 35: 383-385, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661155</a>] [<a href="https://doi.org/10.1006/geno.1996.0373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661155">Sandoval et al. (1996)</a> determined that the SLC6A8 gene contains 13 exons, spans about 8.5 kb of genomic DNA, and is approximately 36 kb centromeric of ALD. Exon 1 occurs within a CpG island, and the gene is transcribed towards the telomeric end. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661155" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#8" class="mim-tip-reference" title="Gregor, P., Nash, S. R., Caron, M. G., Seldin, M. F., Warren, S. T. <strong>Assignment of the creatine transporter gene (SLC6A8) to human chromosome Xq28 telomeric to G6PD.</strong> Genomics 25: 332-333, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7774949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7774949</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80155-f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7774949">Gregor et al. (1995)</a> mapped the creatine transporter gene to the X chromosome using somatic cell hybrid panels. They refined the position to Xq28, distal to the G6PD gene, using a second somatic cell hybrid panel containing portions of the X chromosome as the only human DNA. The finding was consistent with the conclusion that the mouse homolog is very close to G6pd (<a href="#17" class="mim-tip-reference" title="Nash, S. R., Giros, B., Kingsmore, S. F., Rochelle, J. M., Suter, S. T., Gregor, P., Seldin, M. F., Caron, M. G. <strong>Cloning, pharmacological characterization, and genomic localization of the human creatine transporter.</strong> Receptors Channels 2: 165-174, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7953292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7953292</a>]" pmid="7953292">Nash et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7953292+7774949" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using PCR amplification of genomic DNAs from somatic cell hybrid panels and FISH, <a href="#11" class="mim-tip-reference" title="Iyer, G. S., Krahe, R., Goodwin, L. A., Doggett, N. A., Siciliano, M. J., Funanage, V. L., Proujansky, R. <strong>Identification of a testis-expressed creatine transporter gene at 16p11.2 and confirmation of the X-linked locus to Xq28.</strong> Genomics 34: 143-146, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661037</a>] [<a href="https://doi.org/10.1006/geno.1996.0254" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661037">Iyer et al. (1996)</a> confirmed the assignment of SLC6A8, which they called CT1, to Xq28. They also identified another creatine transporter locus, SLC6A10, which they called CT2, on chromosome 16p11.2. However, <a href="#7" class="mim-tip-reference" title="Eichler, E. E., Lu, F., Shen, Y., Antonacci, R., Jurecic, V., Doggett, N. A., Moyzis, R. K., Baldini, A., Gibbs, R. A., Nelson, D. L. <strong>Duplication of a gene-rich cluster between 16p11.1 and Xq28: a novel pericentromeric-directed mechanism for paralogous genome evolution.</strong> Hum. Molec. Genet. 5: 899-912, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817324</a>] [<a href="https://doi.org/10.1093/hmg/5.7.899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8817324">Eichler et al. (1996)</a> and <a href="#10" class="mim-tip-reference" title="Hoglund, P. J., Adzic, D., Scicluna, S. J., Lindblom, J., Fredriksson, R. <strong>The repertoire of solute carriers of family 6: identification of new human and rodent genes.</strong> Biochem. Biophys. Res. Commun. 336: 175-189, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16125675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16125675</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.08.048" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16125675">Hoglund et al. (2005)</a> identified SLC6A10 as pseudogene with a premature stop codon in exon 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16125675+8817324+8661037" 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><a href="#20" class="mim-tip-reference" title="Salomons, G. S., van Dooren, S. J. M., Verhoeven, N. M., Cecil, K. M., Ball, W. S., Degrauw, T. J., Jakobs, C. <strong>X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome.</strong> Am. J. Hum. Genet. 68: 1497-1500, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326334</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11326334[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/320595" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326334">Salomons et al. (2001)</a> described an X-linked cerebral creatine deficiency syndrome (CCDS1; <a href="/entry/300352">300352</a>) due to an arg514-to-ter mutation (<a href="#0001">300036.0001</a>) in the SLC6A8 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11326334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#9" class="mim-tip-reference" title="Hahn, K. A., Salomons, G. S., Tackels-Horne, D., Wood, T. C., Taylor, H. A., Schroer, R. J., Lubs, H. A., Jakobs, C., Olson, R. L., Holden, K. R., Stevenson, R. E., Schwartz, C. E. <strong>X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28.</strong> Am. J. Hum. Genet. 70: 1349-1356, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11898126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11898126</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11898126[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/340092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11898126">Hahn et al. (2002)</a> identified a gly381-to-arg missense mutation in the SLC6A8 gene in a male patient with severe mental retardation with speech and behavioral abnormalities, seizures, short stature, and midface hypoplasia. The underlying mutation, an 1141G-C transversion, had 2 effects: the G381R amino acid substitution and alternative splicing, since the G-to-C transversion occurred at the -1 position of the 5-prime splice junction of intron 7. Two female relatives who were heterozygous for the same SLC6A8 mutation also exhibited mild mental retardation with behavior and learning problems. Male patients with the mutation had highly elevated creatine in their urine and had decreased creatine uptake in fibroblasts, which reflected the deficiency in creatine transport. The ability to measure elevated creatine in urine makes it possible to diagnose SLC6A8 deficiency in male patients with mental retardation of unknown etiology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11898126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p>The report of <a href="#9" class="mim-tip-reference" title="Hahn, K. A., Salomons, G. S., Tackels-Horne, D., Wood, T. C., Taylor, H. A., Schroer, R. J., Lubs, H. A., Jakobs, C., Olson, R. L., Holden, K. R., Stevenson, R. E., Schwartz, C. E. <strong>X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28.</strong> Am. J. Hum. Genet. 70: 1349-1356, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11898126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11898126</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11898126[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/340092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11898126">Hahn et al. (2002)</a>, in conjunction with the reports of arginine:glycine amidinotransferase (AGAT; <a href="/entry/602360">602360</a>) deficiency (<a href="/entry/612718">612718</a>) and of guanidinoacetate methyltransferase (GAMT; <a href="/entry/601240">601240</a>) deficiency (<a href="/entry/612736">612736</a>), clearly indicated the importance of creatine metabolism in brain function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11898126" 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="#19" class="mim-tip-reference" title="Rosenberg, E. H., Almeida, L. S., Kleefstra, T., deGrauw, R. S., Yntema, H. G., Bahi, N., Moraine, C., Ropers, H.-H., Fryns, J.-P., deGrauw, T. J., Jakobs, C., Salomons, G. S. <strong>High prevalence of SLC6A8 deficiency in X-linked mental retardation.</strong> Am. J. Hum. Genet. 75: 97-105, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15154114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15154114</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15154114[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/422102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15154114">Rosenberg et al. (2004)</a> studied the prevalence of SLC6A8 mutations in a panel of 290 patients with nonsyndromic X-linked mental retardation archived by the European XLMR Consortium. They found 6 pathogenic mutations, of which 5 were novel, in a total of 288 patients, showing a prevalence of at least 2.1% (6/288). The novel pathogenic mutations were a nonsense mutation (Y317X; <a href="#0004">300036.0004</a>), and 4 missense mutations, e.g., G87R (<a href="#0005">300036.0005</a>) and C337W (<a href="#0007">300036.0007</a>). They suggested that the frequency of SLC6A8 mutations in the XLMR population is close to that of CGG expansions in FMR1 (<a href="/entry/309550">309550</a>), the gene responsible for fragile X syndrome (<a href="/entry/300624">300624</a>). <a href="#16" class="mim-tip-reference" title="Mandel, J. L. <strong>Comparative frequency of fragile-X (FMR1) and creatine transporter (SLC6A8) mutations in X-linked mental retardation. (Letter)</strong> Am. J. Hum. Genet. 75: 730-731, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15338463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15338463</a>] [<a href="https://doi.org/10.1086/424821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15338463">Mandel (2004)</a> stated that this suggestion is 'certainly incorrect.' <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15154114+15338463" 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="Clark, A. J., Rosenberg, E. H., Almeida, L. S., Wood, T. C., Jakobs, C., Stevenson, R. E., Schwartz, C. E., Salomons, G. S. <strong>X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology.</strong> Hum. Genet. 119: 604-610, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16738945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16738945</a>] [<a href="https://doi.org/10.1007/s00439-006-0162-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16738945">Clark et al. (2006)</a> identified 4 pathogenic and 2 potentially pathogenic mutations in the SLC6A8 gene in 6 of 478 unrelated males with X-linked mental retardation, yielding a frequency of approximately 1%. The authors stated that a total of 18 pathogenic mutations in the SLC6A8 gene had been reported, and suggested that urinary screening for an increased creatine:creatinine ratio could lead to focused mutation testing among appropriate patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16738945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#14" class="mim-tip-reference" title="Lion-Francois, L., Cheillan, D., Pitelet, G., Acquaviva-Bourdain, C., Bussy, G., Cotton, F., Guibaud, L., Gerard, D., Rivier, C., Vianey-Saban, C., Jakobs, C., Salomons, G. S., des Portes, V. <strong>High frequency of creatine deficiency syndromes in patients with unexplained mental retardation.</strong> Neurology 67: 1713-1714, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17101918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17101918</a>] [<a href="https://doi.org/10.1212/01.wnl.0000239153.39710.81" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17101918">Lion-Francois et al. (2006)</a> identified 4 unrelated patients with severe mental retardation due to X-linked creatine deficiency. Four different mutations were identified in the SLC6A8 gene (see, e.g., <a href="#0008">300036.0008</a>; <a href="#0009">300036.0009</a>). Together with a fifth case of creatine deficiency due to mutation in the GAMT gene (<a href="/entry/612736">612736</a>), <a href="#14" class="mim-tip-reference" title="Lion-Francois, L., Cheillan, D., Pitelet, G., Acquaviva-Bourdain, C., Bussy, G., Cotton, F., Guibaud, L., Gerard, D., Rivier, C., Vianey-Saban, C., Jakobs, C., Salomons, G. S., des Portes, V. <strong>High frequency of creatine deficiency syndromes in patients with unexplained mental retardation.</strong> Neurology 67: 1713-1714, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17101918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17101918</a>] [<a href="https://doi.org/10.1212/01.wnl.0000239153.39710.81" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17101918">Lion-Francois et al. (2006)</a> found that the prevalence of cerebral creatine deficiency syndromes was 2.7% in their study population of 188 mentally retarded children. The prevalence rose to 4.4% when only boys were considered. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17101918" 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="#25" class="mim-tip-reference" title="Valayannopoulos, V., Boddaert, N., Chabli, A., Barbier, V., Desguerre, I., Philippe, A., Afenjar, A., Mazzuca, M., Cheillan, D., Munnich, A., de Keyzer, Y., Jakobs, C., Salomons, G. S., de Lonlay, P. <strong>Treatment by oral creatine, L-arginine and L-glycine in six severely affected patients with creatine transporter defect.</strong> J. Inherit. Metab. Dis. 35: 151-157, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21660517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21660517</a>] [<a href="https://doi.org/10.1007/s10545-011-9358-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21660517">Valayannopoulos et al. (2012)</a> reported 3 novel mutations in the SLC6A8 gene in 4 male patients with creatine transporter defect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21660517" 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>
|
|
|
|
<div class="mim-changed mim-change"><p>In a boy with CCDS1, <a href="#15" class="mim-tip-reference" title="Longo, N., Voss, L. A., Frigeni, M., Balakrishnan, B., Pasquali, M. <strong>Response to therapy of creatine transporter deficiency caused by a hypomorphic variant in SLC6A8.</strong> Molec. Genet. Metab. 143: 108595, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39418753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39418753</a>] [<a href="https://doi.org/10.1016/j.ymgme.2024.108595" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="39418753">Longo et al. (2024)</a> identified hemizygosity for a missense mutation in the SLC6A8 gene (R278C; <a href="#0011">300036.0011</a>). The mutation was identified by sequencing of the SLC6A8 gene. Creatine uptake in patient fibroblasts was 25% of normal activity, and cerebral creatine was 20% of the normal range as measured on MRS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39418753" 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></div>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#13" class="mim-tip-reference" title="Levin, M. D., Bianconi, S., Smith, A., Cawley, N. X., Do, A. D., Hammond, D., Grafstein, J. F., Thurm, A., Miller, J., Perreault, J., Noguchi, A., Springer, D., Kozel, B. A., Spurney, C. F., Wassif, C. A., Yu, Z.-X., Schulze, A., Porter, F. D., Hannah-Shmouni, F. <strong>X-linked creatine transporter deficiency results in prolonged QTc and increased sudden death risk in humans and disease model.</strong> Genet. Med. 23: 1864-1872, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34050321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34050321</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34050321[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41436-021-01224-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34050321">Levin et al. (2021)</a> found that hemizygous male Scl6a8-null mice had prolonged QTc and left ventricular dilation by 3 months, as well as increased chamber wall thickness, a phenotype not seen in humans. Left ventricular function was normal and unchanged at 9 months. Mouse exercise stress test showed diminished work capacity, and decreased time to exhaustion. Among hemizygous male Scl6a8-null mice, there was remarkable increase in sudden death: 12 of 28 (43%) hemizygous null mice died unexpectedly, while only 1 of 70 (1.4%) wildtype mice died during 40 weeks of observation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34050321" 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>11 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/300036" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300036[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 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SLC6A8, ARG514TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122453113 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122453113;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs122453113" 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=rs122453113" 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=RCV000012462 OR RCV000623751 OR RCV000713354 OR RCV001257720" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012462, RCV000623751, RCV000713354, RCV001257720" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012462...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male child diagnosed with mild mental retardation at age 6 years who had severe delay in both speech and expressive language function due to cerebral creatine deficiency syndrome-1 (CCDS1; <a href="/entry/300352">300352</a>), <a href="#20" class="mim-tip-reference" title="Salomons, G. S., van Dooren, S. J. M., Verhoeven, N. M., Cecil, K. M., Ball, W. S., Degrauw, T. J., Jakobs, C. <strong>X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome.</strong> Am. J. Hum. Genet. 68: 1497-1500, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326334</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11326334[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/320595" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326334">Salomons et al. (2001)</a> found a hemizygous C-to-T transition in exon 11 of the SLC6A8 gene, resulting in an arg514-to-ter (R514X) mutation. Proton magnetic resonance spectroscopy of the child's brain revealed absence of the creatine signal. However, creatine levels in urine and plasma were increased, and guanidinoacetate levels were normal. In 3 female relatives of the index patient, mild biochemical abnormalities and learning disabilities were present to various extents. The 3 female relatives were heterozygous for this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11326334" 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 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SLC6A8, GLY381ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122453114 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122453114;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs122453114" 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=rs122453114" 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=RCV000012463" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012463" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012463</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#9" class="mim-tip-reference" title="Hahn, K. A., Salomons, G. S., Tackels-Horne, D., Wood, T. C., Taylor, H. A., Schroer, R. J., Lubs, H. A., Jakobs, C., Olson, R. L., Holden, K. R., Stevenson, R. E., Schwartz, C. E. <strong>X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28.</strong> Am. J. Hum. Genet. 70: 1349-1356, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11898126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11898126</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11898126[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/340092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11898126">Hahn et al. (2002)</a> described a family in which 5 males in a sibship of 10 had mental retardation with seizures associated with a defect in creatine metabolism (<a href="/entry/300352">300352</a>). Mutation analysis revealed an 1141G-C transversion at the -1 position of the exon 7/intron 7 splice junction of the SLC6A8 gene. This resulted in the gly381-to-arg missense change and interference with the 5-prime splice junction of intron 7. Subsequent biochemical analyses confirmed a defect in creatine metabolism in this family. The level of urinary creatine was substantially increased in affected male patients and creatine uptake in fibroblasts was decreased. Two sisters of the 5 affected males were heterozygous for the SLC6A8 mutation and exhibited mild mental retardation with behavior and learning problems. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11898126" 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 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SLC6A8, 3-BP DEL, 1221TTC
|
|
</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> rs80338740 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338740;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/rs80338740?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=rs80338740" 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=rs80338740" 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=RCV000012464 OR RCV000483506" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012464, RCV000483506" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012464...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#4" class="mim-tip-reference" title="Bizzi, A., Bugiani, M., Salomons, G. S., Hunneman, D. H., Moroni, I., Estienne, M., Danesi, U., Jakobs, C., Uziel, G. <strong>X-linked creatine deficiency syndrome: a novel mutation in creatine transporter gene SLC6A8.</strong> Ann. Neurol. 52: 227-231, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12210795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12210795</a>] [<a href="https://doi.org/10.1002/ana.10246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12210795">Bizzi et al. (2002)</a> reported a child with creatine deficiency (<a href="/entry/300352">300352</a>) who had severe neurologic disturbances including seizures, behavioral problems, speech delay, and inability to engage in structured play. Proton magnetic resonance spectroscopic imaging showed absence of creatine in the whole brain, which was not corrected by creatine supplementation. Analysis of the SLC6A8 gene showed a hemizygous 3-bp deletion in exon 8, 1221delTTC, resulting in the deletion of a single phenylalanine at residue 408 in a conserved region of the protein. The patient's mother was heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12210795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SLC6A8, 1-BP INS, 950A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569539359 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569539359;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1569539359" 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=rs1569539359" 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=RCV000012465" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012465" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012465</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the index patient of a family with X-linked mental retardation, due to a defect in creatine metabolism (<a href="/entry/300352">300352</a>), <a href="#19" class="mim-tip-reference" title="Rosenberg, E. H., Almeida, L. S., Kleefstra, T., deGrauw, R. S., Yntema, H. G., Bahi, N., Moraine, C., Ropers, H.-H., Fryns, J.-P., deGrauw, T. J., Jakobs, C., Salomons, G. S. <strong>High prevalence of SLC6A8 deficiency in X-linked mental retardation.</strong> Am. J. Hum. Genet. 75: 97-105, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15154114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15154114</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15154114[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/422102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15154114">Rosenberg et al. (2004)</a> found an insertion of adenosine at cDNA position 950 in exon 6 of the SLC6A8 gene (950_951insA), resulting in a premature stop (tyr317 to stop, Y317X). The truncated mutant protein was predicted to lack 319 C-terminal residues, including transmembrane domains VII through XII, and to be unstable and/or inappropriately folded and therefore completely inactive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15154114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0005" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SLC6A8, GLY87ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122453115 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122453115;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs122453115" 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=rs122453115" 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=RCV000012466 OR RCV001508970" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012466, RCV001508970" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012466...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the index patient of a family with X-linked mental retardation due to a defect in creatine metabolism (<a href="/entry/300352">300352</a>), <a href="#19" class="mim-tip-reference" title="Rosenberg, E. H., Almeida, L. S., Kleefstra, T., deGrauw, R. S., Yntema, H. G., Bahi, N., Moraine, C., Ropers, H.-H., Fryns, J.-P., deGrauw, T. J., Jakobs, C., Salomons, G. S. <strong>High prevalence of SLC6A8 deficiency in X-linked mental retardation.</strong> Am. J. Hum. Genet. 75: 97-105, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15154114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15154114</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15154114[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/422102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15154114">Rosenberg et al. (2004)</a> found a G-to-A transition at cDNA position 259 in exon 1 of the SLC6A8 gene that gave rise to a gly87-to-arg (G87R) amino acid substitution. This mutation changes one of 3 glycines that make up a short repeat between transmembrane domains I and II, in a small intracellular loop that is highly conserved among all known creatine transporters and within the neurotransmitter transporter family SLC6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15154114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0006" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SLC6A8, IVS1AS, A-G, -2
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569539244 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569539244;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1569539244" 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=rs1569539244" 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=RCV000012467" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012467" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012467</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient with X-linked creatine deficiency syndrome and severe mental retardation (<a href="/entry/300352">300352</a>), <a href="#22" class="mim-tip-reference" title="Schiaffino, M. C., Bellini, C., Costabello, L., Caruso, U., Jakobs, C., Salomons, G. S., Bonioli, E. <strong>X-linked creatine transporter deficiency: clinical description of a patient with a novel SLC6A8 gene mutation.</strong> Neurogenetics 6: 165-168, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16086185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16086185</a>] [<a href="https://doi.org/10.1007/s10048-005-0002-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16086185">Schiaffino et al. (2005)</a> identified an A-to-G transition in intron 1 of the SLC6A8 gene, resulting in skipping of the first 21 amino acids of exon 2. These residues form the second transmembrane domain, which is highly conserved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16086185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SLC6A8, CYS337TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122453116 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122453116;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs122453116" 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=rs122453116" 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=RCV000012468" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012468" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012468</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with X-linked creatine deficiency syndrome and mental retardation (<a href="/entry/300352">300352</a>), <a href="#19" class="mim-tip-reference" title="Rosenberg, E. H., Almeida, L. S., Kleefstra, T., deGrauw, R. S., Yntema, H. G., Bahi, N., Moraine, C., Ropers, H.-H., Fryns, J.-P., deGrauw, T. J., Jakobs, C., Salomons, G. S. <strong>High prevalence of SLC6A8 deficiency in X-linked mental retardation.</strong> Am. J. Hum. Genet. 75: 97-105, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15154114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15154114</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15154114[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/422102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15154114">Rosenberg et al. (2004)</a> identified a 1011C-G transversion, resulting in a cys337-to-trp (C337W) substitution in the highly conserved intracellular loop between transmembrane domains VI and VII. In the urine of the 2 patients, an increased creatine:creatinine ratio was found, which is a biochemical hallmark of SLC6A8 deficiency. The sister of the patients was a carrier of the C337W mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15154114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SLC6A8, GLY132VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122453117 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122453117;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs122453117" 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=rs122453117" 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=RCV000012469" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012469" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012469</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old boy with creatine deficiency syndrome and severe mental retardation (<a href="/entry/300352">300352</a>), <a href="#14" class="mim-tip-reference" title="Lion-Francois, L., Cheillan, D., Pitelet, G., Acquaviva-Bourdain, C., Bussy, G., Cotton, F., Guibaud, L., Gerard, D., Rivier, C., Vianey-Saban, C., Jakobs, C., Salomons, G. S., des Portes, V. <strong>High frequency of creatine deficiency syndromes in patients with unexplained mental retardation.</strong> Neurology 67: 1713-1714, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17101918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17101918</a>] [<a href="https://doi.org/10.1212/01.wnl.0000239153.39710.81" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17101918">Lion-Francois et al. (2006)</a> identified a 395G-T transversion in the SLC6A8 gene, resulting in a gly132-to-val (G132V) substitution. The patient had delayed onset of walking and autistic behavior. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17101918" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SLC6A8, CYS491TRP
|
|
</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> rs122453118 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122453118;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/rs122453118?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=rs122453118" 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=rs122453118" 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=RCV000012470" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012470" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012470</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old boy with creatine deficiency syndrome and severe mental retardation (<a href="/entry/300352">300352</a>), <a href="#14" class="mim-tip-reference" title="Lion-Francois, L., Cheillan, D., Pitelet, G., Acquaviva-Bourdain, C., Bussy, G., Cotton, F., Guibaud, L., Gerard, D., Rivier, C., Vianey-Saban, C., Jakobs, C., Salomons, G. S., des Portes, V. <strong>High frequency of creatine deficiency syndromes in patients with unexplained mental retardation.</strong> Neurology 67: 1713-1714, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17101918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17101918</a>] [<a href="https://doi.org/10.1212/01.wnl.0000239153.39710.81" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17101918">Lion-Francois et al. (2006)</a> identified a 1473C-G transversion in the SLC6A8 gene, resulting in a cys491-to-trp (C491W) substitution. The patient had delayed onset of walking, seizures, and autistic features. Brain imaging showed atrophy of the left caudate and hippocampus and a thin corpus callosum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17101918" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
SLC6A8, 3-BP DEL, 1006AAC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs782433037 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs782433037;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs782433037" 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=rs782433037" 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=RCV000012471 OR RCV000255812" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012471, RCV000255812" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012471...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old boy with creatine deficiency syndrome (<a href="/entry/300352">300352</a>), <a href="#5" class="mim-tip-reference" title="Clark, A. J., Rosenberg, E. H., Almeida, L. S., Wood, T. C., Jakobs, C., Stevenson, R. E., Schwartz, C. E., Salomons, G. S. <strong>X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology.</strong> Hum. Genet. 119: 604-610, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16738945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16738945</a>] [<a href="https://doi.org/10.1007/s00439-006-0162-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16738945">Clark et al. (2006)</a> identified a hemizygous 3-bp deletion (1006delAAC) in exon 6 of the SLC6A8 gene, resulting in a deletion of a highly conserved residue asn336. The patient had moderate mental retardation, attention deficit-hyperactivity disorder, microcephaly, and tall stature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16738945" 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="#3" class="mim-tip-reference" title="Battini, R., Chilosi, A., Mei, D., Casarano, M., Alessandri, M. G., Leuzzi, V., Ferretti, G., Tosetti, M., Bianchi, M. C., Cioni, G. <strong>Mental retardation and verbal dyspraxia in a new patient with de novo creatine transporter (SLC6A8) mutation.</strong> Am. J. Med. Genet. 143A: 1771-1774, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17603797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17603797</a>] [<a href="https://doi.org/10.1002/ajmg.a.31827" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17603797">Battini et al. (2007)</a> identified the 1006delAAC mutation in a 9.5-year-old Italian boy with mental retardation and verbal dyspraxia. He had delayed psychomotor development, hypotonia, seizures, and severe language deficit with oral-motor dyspraxia, irritability, and temper tantrums. Detailed language evaluation showed problems in picture naming and phonetics, whereas receptive vocabulary was less severely affected. Social interaction was good despite the severe expressive limitation. <a href="#3" class="mim-tip-reference" title="Battini, R., Chilosi, A., Mei, D., Casarano, M., Alessandri, M. G., Leuzzi, V., Ferretti, G., Tosetti, M., Bianchi, M. C., Cioni, G. <strong>Mental retardation and verbal dyspraxia in a new patient with de novo creatine transporter (SLC6A8) mutation.</strong> Am. J. Med. Genet. 143A: 1771-1774, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17603797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17603797</a>] [<a href="https://doi.org/10.1002/ajmg.a.31827" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17603797">Battini et al. (2007)</a> noted that the phenotype in their patient was different than that reported by <a href="#5" class="mim-tip-reference" title="Clark, A. J., Rosenberg, E. H., Almeida, L. S., Wood, T. C., Jakobs, C., Stevenson, R. E., Schwartz, C. E., Salomons, G. S. <strong>X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology.</strong> Hum. Genet. 119: 604-610, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16738945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16738945</a>] [<a href="https://doi.org/10.1007/s00439-006-0162-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16738945">Clark et al. (2006)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16738945+17603797" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong><div class="mim-changed mim-change">.0011 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</div></strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
<div class="mim-changed mim-change">SLC6A8, ARG278CYS</div>
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004799653" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004799653" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004799653</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a boy with creatine deficiency syndrome (CCDS1; <a href="/entry/300352">300352</a>), <a href="#15" class="mim-tip-reference" title="Longo, N., Voss, L. A., Frigeni, M., Balakrishnan, B., Pasquali, M. <strong>Response to therapy of creatine transporter deficiency caused by a hypomorphic variant in SLC6A8.</strong> Molec. Genet. Metab. 143: 108595, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39418753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39418753</a>] [<a href="https://doi.org/10.1016/j.ymgme.2024.108595" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="39418753">Longo et al. (2024)</a> identified hemizygosity for a c.832C-T transition in the SLC6A8 gene, resulting in an arg278-to-cys (R278C) substitution. The mutation was identified with sequencing of the SLC6A8 gene. The mutation was reported once (in this patient) in the gnomAD database at an allele frequency of 1/1096567. Creatine uptake in patient fibroblasts was 25% of normal activity and cerebral creatine was 20% of normal as measured on MRS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39418753" 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></div>
|
|
</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="Abplanalp2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Abplanalp, J., Laczko, E., Philp, N. J., Neidhardt, J., Zuercher, J., Braun, P., Schorderet, D. F., Munier, F. L., Verrey, F., Berger, W., Camargo, S. M. R., Kloeckener-Gruissem, B.
|
|
<strong>The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter.</strong>
|
|
Hum. Molec. Genet. 22: 3218-3226, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23578822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23578822</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23578822[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23578822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddt175" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Barnwell1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barnwell, L. F. S., Chaudhuri, G., Townsel, J. G.
|
|
<strong>Cloning and sequencing of a cDNA encoding a novel member of the human brain GABA/noradrenaline neurotransmitter transporter family.</strong>
|
|
Gene 159: 287-288, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7622069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7622069</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7622069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0378-1119(95)00104-e" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Battini2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Battini, R., Chilosi, A., Mei, D., Casarano, M., Alessandri, M. G., Leuzzi, V., Ferretti, G., Tosetti, M., Bianchi, M. C., Cioni, G.
|
|
<strong>Mental retardation and verbal dyspraxia in a new patient with de novo creatine transporter (SLC6A8) mutation.</strong>
|
|
Am. J. Med. Genet. 143A: 1771-1774, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17603797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17603797</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17603797" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.31827" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Bizzi2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bizzi, A., Bugiani, M., Salomons, G. S., Hunneman, D. H., Moroni, I., Estienne, M., Danesi, U., Jakobs, C., Uziel, G.
|
|
<strong>X-linked creatine deficiency syndrome: a novel mutation in creatine transporter gene SLC6A8.</strong>
|
|
Ann. Neurol. 52: 227-231, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12210795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12210795</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12210795" 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/ana.10246" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Clark2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Clark, A. J., Rosenberg, E. H., Almeida, L. S., Wood, T. C., Jakobs, C., Stevenson, R. E., Schwartz, C. E., Salomons, G. S.
|
|
<strong>X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology.</strong>
|
|
Hum. Genet. 119: 604-610, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16738945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16738945</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16738945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00439-006-0162-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Dai1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dai, W., Vinnakota, S., Qian, X., Kunze, D. L., Sarkar, H. K.
|
|
<strong>Molecular characterization of the human CRT-1 creatine transporter expressed in Xenopus oocytes.</strong>
|
|
Arch. Biochem. Biophys. 361: 75-84, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9882430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9882430</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9882430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/abbi.1998.0959" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Eichler1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eichler, E. E., Lu, F., Shen, Y., Antonacci, R., Jurecic, V., Doggett, N. A., Moyzis, R. K., Baldini, A., Gibbs, R. A., Nelson, D. L.
|
|
<strong>Duplication of a gene-rich cluster between 16p11.1 and Xq28: a novel pericentromeric-directed mechanism for paralogous genome evolution.</strong>
|
|
Hum. Molec. Genet. 5: 899-912, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817324</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8817324" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/5.7.899" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Gregor1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gregor, P., Nash, S. R., Caron, M. G., Seldin, M. F., Warren, S. T.
|
|
<strong>Assignment of the creatine transporter gene (SLC6A8) to human chromosome Xq28 telomeric to G6PD.</strong>
|
|
Genomics 25: 332-333, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7774949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7774949</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7774949" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(95)80155-f" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Hahn2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hahn, K. A., Salomons, G. S., Tackels-Horne, D., Wood, T. C., Taylor, H. A., Schroer, R. J., Lubs, H. A., Jakobs, C., Olson, R. L., Holden, K. R., Stevenson, R. E., Schwartz, C. E.
|
|
<strong>X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28.</strong>
|
|
Am. J. Hum. Genet. 70: 1349-1356, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11898126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11898126</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11898126[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11898126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/340092" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Hoglund2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hoglund, P. J., Adzic, D., Scicluna, S. J., Lindblom, J., Fredriksson, R.
|
|
<strong>The repertoire of solute carriers of family 6: identification of new human and rodent genes.</strong>
|
|
Biochem. Biophys. Res. Commun. 336: 175-189, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16125675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16125675</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16125675" 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.bbrc.2005.08.048" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Iyer1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iyer, G. S., Krahe, R., Goodwin, L. A., Doggett, N. A., Siciliano, M. J., Funanage, V. L., Proujansky, R.
|
|
<strong>Identification of a testis-expressed creatine transporter gene at 16p11.2 and confirmation of the X-linked locus to Xq28.</strong>
|
|
Genomics 34: 143-146, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661037</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661037" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1996.0254" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Ji2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ji, L., Zhao, X., Zhang, B., Kang, L., Song, W., Zhao, B., Xie, W., Chen, L., Hu, X.
|
|
<strong>Slc6a8-mediated creatine uptake and accumulation reprogram macrophage polarization via regulating cytokine responses.</strong>
|
|
Immunity 51: 272-284, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31399282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31399282</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31399282" 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.immuni.2019.06.007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Levin2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Levin, M. D., Bianconi, S., Smith, A., Cawley, N. X., Do, A. D., Hammond, D., Grafstein, J. F., Thurm, A., Miller, J., Perreault, J., Noguchi, A., Springer, D., Kozel, B. A., Spurney, C. F., Wassif, C. A., Yu, Z.-X., Schulze, A., Porter, F. D., Hannah-Shmouni, F.
|
|
<strong>X-linked creatine transporter deficiency results in prolonged QTc and increased sudden death risk in humans and disease model.</strong>
|
|
Genet. Med. 23: 1864-1872, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34050321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34050321</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34050321[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34050321" 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/s41436-021-01224-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Lion-Francois2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lion-Francois, L., Cheillan, D., Pitelet, G., Acquaviva-Bourdain, C., Bussy, G., Cotton, F., Guibaud, L., Gerard, D., Rivier, C., Vianey-Saban, C., Jakobs, C., Salomons, G. S., des Portes, V.
|
|
<strong>High frequency of creatine deficiency syndromes in patients with unexplained mental retardation.</strong>
|
|
Neurology 67: 1713-1714, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17101918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17101918</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17101918" 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.0000239153.39710.81" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Longo2024" class="mim-anchor"></a>
|
|
<div class="mim-changed mim-change">
|
|
<p class="mim-text-font">
|
|
Longo, N., Voss, L. A., Frigeni, M., Balakrishnan, B., Pasquali, M.
|
|
<strong>Response to therapy of creatine transporter deficiency caused by a hypomorphic variant in SLC6A8.</strong>
|
|
Molec. Genet. Metab. 143: 108595, 2024.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39418753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39418753</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39418753" 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.ymgme.2024.108595" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Mandel2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mandel, J. L.
|
|
<strong>Comparative frequency of fragile-X (FMR1) and creatine transporter (SLC6A8) mutations in X-linked mental retardation. (Letter)</strong>
|
|
Am. J. Hum. Genet. 75: 730-731, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15338463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15338463</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15338463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/424821" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Nash1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nash, S. R., Giros, B., Kingsmore, S. F., Rochelle, J. M., Suter, S. T., Gregor, P., Seldin, M. F., Caron, M. G.
|
|
<strong>Cloning, pharmacological characterization, and genomic localization of the human creatine transporter.</strong>
|
|
Receptors Channels 2: 165-174, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7953292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7953292</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7953292" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Peral2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peral, M. J., Garcia-Delgado, M., Calonge, M. L., Duran, J. M., De La Horra, M. C., Wallimann, T., Speer, O., Ilundain, A. A.
|
|
<strong>Human, rat and chicken small intestinal Na(+)-Cl(-)-creatine transporter: functional, molecular characterization and localization.</strong>
|
|
J. Physiol. 545: 133-144, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12433955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12433955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12433955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12433955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1113/jphysiol.2002.026377" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Rosenberg2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rosenberg, E. H., Almeida, L. S., Kleefstra, T., deGrauw, R. S., Yntema, H. G., Bahi, N., Moraine, C., Ropers, H.-H., Fryns, J.-P., deGrauw, T. J., Jakobs, C., Salomons, G. S.
|
|
<strong>High prevalence of SLC6A8 deficiency in X-linked mental retardation.</strong>
|
|
Am. J. Hum. Genet. 75: 97-105, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15154114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15154114</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15154114[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15154114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/422102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Salomons2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Salomons, G. S., van Dooren, S. J. M., Verhoeven, N. M., Cecil, K. M., Ball, W. S., Degrauw, T. J., Jakobs, C.
|
|
<strong>X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome.</strong>
|
|
Am. J. Hum. Genet. 68: 1497-1500, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326334</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11326334[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11326334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/320595" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Sandoval1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sandoval, N., Bauer, D., Brenner, V., Coy, J. F., Drescher, B., Kioschis, P., Korn, B., Nyakatura, G., Poustka, A., Reichwald, K., Rosenthal, A., Platzer, M.
|
|
<strong>The genomic organization of a human creatine transporter (CRTR) gene located in Xq28.</strong>
|
|
Genomics 35: 383-385, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661155</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661155" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1996.0373" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Schiaffino2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schiaffino, M. C., Bellini, C., Costabello, L., Caruso, U., Jakobs, C., Salomons, G. S., Bonioli, E.
|
|
<strong>X-linked creatine transporter deficiency: clinical description of a patient with a novel SLC6A8 gene mutation.</strong>
|
|
Neurogenetics 6: 165-168, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16086185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16086185</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16086185" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10048-005-0002-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Schlattner2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schlattner, U., Mockli, N., Speer, O., Werner, S., Wallimann, T.
|
|
<strong>Creatine kinase and creatine transporter in normal, wounded, and diseased skin.</strong>
|
|
J. Invest. Derm. 118: 416-423, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11874479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11874479</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11874479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.0022-202x.2001.01697.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Shojaiefard2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shojaiefard, M., Christie, D. L., Lang, F.
|
|
<strong>Stimulation of the creatine kinase transporter SLC6A8 by the protein kinases SGK1 and SGK3.</strong>
|
|
Biochem. Biophys. Res. Commun. 334: 742-746, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16036218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16036218</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16036218" 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.bbrc.2005.06.164" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Valayannopoulos2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Valayannopoulos, V., Boddaert, N., Chabli, A., Barbier, V., Desguerre, I., Philippe, A., Afenjar, A., Mazzuca, M., Cheillan, D., Munnich, A., de Keyzer, Y., Jakobs, C., Salomons, G. S., de Lonlay, P.
|
|
<strong>Treatment by oral creatine, L-arginine and L-glycine in six severely affected patients with creatine transporter defect.</strong>
|
|
J. Inherit. Metab. Dis. 35: 151-157, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21660517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21660517</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21660517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10545-011-9358-9" 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">
|
|
Hilary J. Vernon - updated : 12/06/2024
|
|
</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">
|
|
Ada Hamosh - updated : 09/17/2024<br>Bao Lige - updated : 01/06/2020<br>Patricia A. Hartz - updated : 2/9/2015<br>Ada Hamosh - updated : 11/25/2014<br>Cassandra L. Kniffin - updated : 9/3/2008<br>Patricia A. Hartz - updated : 5/2/2008<br>Cassandra L. Kniffin - updated : 2/7/2008<br>Patricia A. Hartz - updated : 12/17/2007<br>Cassandra L. Kniffin - updated : 8/28/2006<br>Matthew B. Gross - updated : 5/12/2006<br>Marla J. F. O'Neill - updated : 11/23/2005<br>Cassandra L. Kniffin - updated : 11/9/2005<br>Victor A. McKusick - updated : 9/14/2004<br>Victor A. McKusick - updated : 6/30/2004<br>Cassandra L. Kniffin - updated : 10/2/2002<br>Victor A. McKusick - updated : 5/17/2002<br>Victor A. McKusick - updated : 6/20/2001<br>Alan F. Scott - updated : 8/21/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 2/25/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 12/09/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 12/06/2024<br>alopez : 09/17/2024<br>mgross : 01/06/2020<br>mgross : 02/09/2015<br>mgross : 2/9/2015<br>mcolton : 2/9/2015<br>alopez : 11/25/2014<br>carol : 7/17/2013<br>ckniffin : 7/16/2013<br>carol : 4/20/2009<br>wwang : 9/24/2008<br>ckniffin : 9/3/2008<br>mgross : 5/2/2008<br>wwang : 2/20/2008<br>ckniffin : 2/7/2008<br>mgross : 12/19/2007<br>terry : 12/17/2007<br>carol : 11/27/2006<br>wwang : 9/5/2006<br>ckniffin : 8/28/2006<br>mgross : 5/12/2006<br>wwang : 11/23/2005<br>wwang : 11/23/2005<br>wwang : 11/22/2005<br>ckniffin : 11/9/2005<br>tkritzer : 9/15/2004<br>terry : 9/14/2004<br>alopez : 7/7/2004<br>terry : 6/30/2004<br>terry : 11/22/2002<br>carol : 10/31/2002<br>tkritzer : 10/25/2002<br>tkritzer : 10/25/2002<br>ckniffin : 10/2/2002<br>alopez : 5/24/2002<br>terry : 5/17/2002<br>carol : 3/8/2002<br>terry : 3/8/2002<br>carol : 8/6/2001<br>mcapotos : 6/27/2001<br>mcapotos : 6/26/2001<br>mcapotos : 6/22/2001<br>terry : 6/20/2001<br>mark : 8/21/1996<br>marlene : 8/19/1996<br>terry : 6/5/1996<br>terry : 6/3/1996<br>terry : 5/16/1996<br>joanna : 2/26/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 300036
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, CREATINE), MEMBER 8; SLC6A8
|
|
|
|
</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">
|
|
CREATINE TRANSPORTER; CT1; CRTR; CRT
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: SLC6A8</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 698290008;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: Xq28
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : X:153,687,926-153,696,593 </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">
|
|
Xq28
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cerebral creatine deficiency syndrome 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
300352
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The creatine-phosphocreatine shuttle has important functions in the temporal and spatial maintenance of the energy supply to skeletal and cardiac muscle. Muscle cells do not synthesize creatine, but take it up via a special sodium-dependent transporter, the creatine transporter (SLC6A8). Thus, SLC6A8 has an important role in muscle physiology, and inhibition of creatine transport in experimental animals causes muscle weakness (Gregor et al., 1995). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using rat Crt1 to probe a human hippocampus cDNA library, Barnwell et al. (1995) obtained 2 groups of CRT clones, which they called CRT1 and CRT2. CRT1 is homologous to rat Crt1. CRT2 encodes a deduced 732-amino acid protein with a unique N-terminal segment and 3 short insertions in its C-terminal half that are not found in CRT1. </p><p>Dai et al. (1999) obtained a CRT1 clone from a human heart cDNA library. The deduced protein contains pro285 (P285) rather than ala285 (A285), which was predicted from a CRT1 clone obtained from a human kidney cDNA library by Nash et al. (1994). </p><p>Using Western blot analysis, Peral et al. (2002) detected robust expression of an apparent 57-kD CRT protein in human brush border cells. Weaker expression of CRT proteins with apparent molecular masses of 72 and 52 kD was detected in human heart. Immunofluorescence analysis of human ileum detected specific staining at apical membranes of cells lining the villus. In situ hybridization of chicken small intestine showed Crt expression restricted to cells lining the villus, with no Crt expression in crypt cells. </p><p>Using RT-PCR analysis, Abplanalp et al. (2013) detected robust SLC6A8 expression in human kidney, retina, brain, heart, and muscle, with weaker expression in lens. In contrast, SLC16A12 (611910), another creatine transporter, was highly expressed in kidney and retina only, with weaker expression in other tissues. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By assaying Xenopus oocytes injected with cRNAs, Dai et al. (1999) found that human CRT1 induced saturable Na(+)- and Cl(-)-dependent creatine uptake. CRT1 forms with P285 were as efficient in creatine uptake as those with A285. However, the P285 form had higher sensitivity to guanidinoethane sulfonic acid, a potent inhibitor of taurine transport, than the A285 form. The substitution did not alter CRT1 sensitivity to other inhibitors tested. Kinetic analysis revealed that 2 Na+ and 1 Cl- were required for electrogenic transport of 1 creatine molecule. </p><p>Using Western blot analysis and confocal immunohistochemistry, Schlattner et al. (2002) investigated the localization of creatine kinases (CKs) in mouse and human skin under healthy and pathologic conditions. In mouse skin, they found high amounts of cytosolic brain CK (CKB; 123280) coexpressed with lower amounts of ubiquitous mitochondrial CK (CKMT1B; 123290), both mainly localized in suprabasal layers of the dermis, different cell types of hair follicles, sebaceous glands, and the subcutaneous panniculus carnosus muscle. Except for sebaceous glands, these cells also expressed CRT. Western blot analysis showed that Ckb and Crt were upregulated about 3-fold immediately after wounding of mouse skin, whereas the amount of Ckmt1b increased 10 to 15 days after wounding. Healthy and psoriatic human skin showed a similar coexpression pattern of CKB, CKMT1B, and CRT, with CRT upregulated in psoriasis. </p><p>Shojaiefard et al. (2005) showed that human SGK1 (602958) or SGK3 (607591) stimulated creatine-induced currents in Xenopus oocytes heterologously expressing human SLC6A8. </p><p>Ji et al. (2019) found that mouse macrophages maintained high intracellular creatine through Slc6a8-mediated uptake and that macrophage polarization was coupled with changes in creatine uptake. Creatine was dispensable for macrophage development and functionality in steady state, but it inhibited polarization of Ifn-gamma (IFNG; 147570)-activated macrophages by suppressing JAK (see 147795)-Stat1 (600555) signaling and Stat1 target gene activation. Consequently, creatine depletion promoted polarization of Ifn-gamma activated macrophages and enhanced host defense against infection by Listeria monocytogenes. Creatine supported polarization of Il4 (147780)-activated macrophages by promoting expression of arginase-1 (ARG1; 608313) through ATP-dependent SWI/SNF (see 600014)-mediated chromatin remodeling. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Sandoval et al. (1996) determined that the SLC6A8 gene contains 13 exons, spans about 8.5 kb of genomic DNA, and is approximately 36 kb centromeric of ALD. Exon 1 occurs within a CpG island, and the gene is transcribed towards the telomeric end. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Gregor et al. (1995) mapped the creatine transporter gene to the X chromosome using somatic cell hybrid panels. They refined the position to Xq28, distal to the G6PD gene, using a second somatic cell hybrid panel containing portions of the X chromosome as the only human DNA. The finding was consistent with the conclusion that the mouse homolog is very close to G6pd (Nash et al., 1994). </p><p>Using PCR amplification of genomic DNAs from somatic cell hybrid panels and FISH, Iyer et al. (1996) confirmed the assignment of SLC6A8, which they called CT1, to Xq28. They also identified another creatine transporter locus, SLC6A10, which they called CT2, on chromosome 16p11.2. However, Eichler et al. (1996) and Hoglund et al. (2005) identified SLC6A10 as pseudogene with a premature stop codon in exon 4. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Salomons et al. (2001) described an X-linked cerebral creatine deficiency syndrome (CCDS1; 300352) due to an arg514-to-ter mutation (300036.0001) in the SLC6A8 gene. </p><p>Hahn et al. (2002) identified a gly381-to-arg missense mutation in the SLC6A8 gene in a male patient with severe mental retardation with speech and behavioral abnormalities, seizures, short stature, and midface hypoplasia. The underlying mutation, an 1141G-C transversion, had 2 effects: the G381R amino acid substitution and alternative splicing, since the G-to-C transversion occurred at the -1 position of the 5-prime splice junction of intron 7. Two female relatives who were heterozygous for the same SLC6A8 mutation also exhibited mild mental retardation with behavior and learning problems. Male patients with the mutation had highly elevated creatine in their urine and had decreased creatine uptake in fibroblasts, which reflected the deficiency in creatine transport. The ability to measure elevated creatine in urine makes it possible to diagnose SLC6A8 deficiency in male patients with mental retardation of unknown etiology. </p><p>The report of Hahn et al. (2002), in conjunction with the reports of arginine:glycine amidinotransferase (AGAT; 602360) deficiency (612718) and of guanidinoacetate methyltransferase (GAMT; 601240) deficiency (612736), clearly indicated the importance of creatine metabolism in brain function. </p><p>Rosenberg et al. (2004) studied the prevalence of SLC6A8 mutations in a panel of 290 patients with nonsyndromic X-linked mental retardation archived by the European XLMR Consortium. They found 6 pathogenic mutations, of which 5 were novel, in a total of 288 patients, showing a prevalence of at least 2.1% (6/288). The novel pathogenic mutations were a nonsense mutation (Y317X; 300036.0004), and 4 missense mutations, e.g., G87R (300036.0005) and C337W (300036.0007). They suggested that the frequency of SLC6A8 mutations in the XLMR population is close to that of CGG expansions in FMR1 (309550), the gene responsible for fragile X syndrome (300624). Mandel (2004) stated that this suggestion is 'certainly incorrect.' </p><p>Clark et al. (2006) identified 4 pathogenic and 2 potentially pathogenic mutations in the SLC6A8 gene in 6 of 478 unrelated males with X-linked mental retardation, yielding a frequency of approximately 1%. The authors stated that a total of 18 pathogenic mutations in the SLC6A8 gene had been reported, and suggested that urinary screening for an increased creatine:creatinine ratio could lead to focused mutation testing among appropriate patients. </p><p>Lion-Francois et al. (2006) identified 4 unrelated patients with severe mental retardation due to X-linked creatine deficiency. Four different mutations were identified in the SLC6A8 gene (see, e.g., 300036.0008; 300036.0009). Together with a fifth case of creatine deficiency due to mutation in the GAMT gene (612736), Lion-Francois et al. (2006) found that the prevalence of cerebral creatine deficiency syndromes was 2.7% in their study population of 188 mentally retarded children. The prevalence rose to 4.4% when only boys were considered. </p><p>Valayannopoulos et al. (2012) reported 3 novel mutations in the SLC6A8 gene in 4 male patients with creatine transporter defect. </p><p>In a boy with CCDS1, Longo et al. (2024) identified hemizygosity for a missense mutation in the SLC6A8 gene (R278C; 300036.0011). The mutation was identified by sequencing of the SLC6A8 gene. Creatine uptake in patient fibroblasts was 25% of normal activity, and cerebral creatine was 20% of the normal range as measured on MRS. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Levin et al. (2021) found that hemizygous male Scl6a8-null mice had prolonged QTc and left ventricular dilation by 3 months, as well as increased chamber wall thickness, a phenotype not seen in humans. Left ventricular function was normal and unchanged at 9 months. Mouse exercise stress test showed diminished work capacity, and decreased time to exhaustion. Among hemizygous male Scl6a8-null mice, there was remarkable increase in sudden death: 12 of 28 (43%) hemizygous null mice died unexpectedly, while only 1 of 70 (1.4%) wildtype mice died during 40 weeks of observation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>11 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, ARG514TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs122453113,
|
|
|
|
|
|
|
|
ClinVar: RCV000012462, RCV000623751, RCV000713354, RCV001257720
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male child diagnosed with mild mental retardation at age 6 years who had severe delay in both speech and expressive language function due to cerebral creatine deficiency syndrome-1 (CCDS1; 300352), Salomons et al. (2001) found a hemizygous C-to-T transition in exon 11 of the SLC6A8 gene, resulting in an arg514-to-ter (R514X) mutation. Proton magnetic resonance spectroscopy of the child's brain revealed absence of the creatine signal. However, creatine levels in urine and plasma were increased, and guanidinoacetate levels were normal. In 3 female relatives of the index patient, mild biochemical abnormalities and learning disabilities were present to various extents. The 3 female relatives were heterozygous for this mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, GLY381ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs122453114,
|
|
|
|
|
|
|
|
ClinVar: RCV000012463
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Hahn et al. (2002) described a family in which 5 males in a sibship of 10 had mental retardation with seizures associated with a defect in creatine metabolism (300352). Mutation analysis revealed an 1141G-C transversion at the -1 position of the exon 7/intron 7 splice junction of the SLC6A8 gene. This resulted in the gly381-to-arg missense change and interference with the 5-prime splice junction of intron 7. Subsequent biochemical analyses confirmed a defect in creatine metabolism in this family. The level of urinary creatine was substantially increased in affected male patients and creatine uptake in fibroblasts was decreased. Two sisters of the 5 affected males were heterozygous for the SLC6A8 mutation and exhibited mild mental retardation with behavior and learning problems. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, 3-BP DEL, 1221TTC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80338740,
|
|
|
|
|
|
gnomAD: rs80338740,
|
|
|
|
|
|
ClinVar: RCV000012464, RCV000483506
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bizzi et al. (2002) reported a child with creatine deficiency (300352) who had severe neurologic disturbances including seizures, behavioral problems, speech delay, and inability to engage in structured play. Proton magnetic resonance spectroscopic imaging showed absence of creatine in the whole brain, which was not corrected by creatine supplementation. Analysis of the SLC6A8 gene showed a hemizygous 3-bp deletion in exon 8, 1221delTTC, resulting in the deletion of a single phenylalanine at residue 408 in a conserved region of the protein. The patient's mother was heterozygous for the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, 1-BP INS, 950A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569539359,
|
|
|
|
|
|
|
|
ClinVar: RCV000012465
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the index patient of a family with X-linked mental retardation, due to a defect in creatine metabolism (300352), Rosenberg et al. (2004) found an insertion of adenosine at cDNA position 950 in exon 6 of the SLC6A8 gene (950_951insA), resulting in a premature stop (tyr317 to stop, Y317X). The truncated mutant protein was predicted to lack 319 C-terminal residues, including transmembrane domains VII through XII, and to be unstable and/or inappropriately folded and therefore completely inactive. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, GLY87ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs122453115,
|
|
|
|
|
|
|
|
ClinVar: RCV000012466, RCV001508970
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the index patient of a family with X-linked mental retardation due to a defect in creatine metabolism (300352), Rosenberg et al. (2004) found a G-to-A transition at cDNA position 259 in exon 1 of the SLC6A8 gene that gave rise to a gly87-to-arg (G87R) amino acid substitution. This mutation changes one of 3 glycines that make up a short repeat between transmembrane domains I and II, in a small intracellular loop that is highly conserved among all known creatine transporters and within the neurotransmitter transporter family SLC6. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, IVS1AS, A-G, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569539244,
|
|
|
|
|
|
|
|
ClinVar: RCV000012467
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient with X-linked creatine deficiency syndrome and severe mental retardation (300352), Schiaffino et al. (2005) identified an A-to-G transition in intron 1 of the SLC6A8 gene, resulting in skipping of the first 21 amino acids of exon 2. These residues form the second transmembrane domain, which is highly conserved. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, CYS337TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs122453116,
|
|
|
|
|
|
|
|
ClinVar: RCV000012468
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with X-linked creatine deficiency syndrome and mental retardation (300352), Rosenberg et al. (2004) identified a 1011C-G transversion, resulting in a cys337-to-trp (C337W) substitution in the highly conserved intracellular loop between transmembrane domains VI and VII. In the urine of the 2 patients, an increased creatine:creatinine ratio was found, which is a biochemical hallmark of SLC6A8 deficiency. The sister of the patients was a carrier of the C337W mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, GLY132VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs122453117,
|
|
|
|
|
|
|
|
ClinVar: RCV000012469
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old boy with creatine deficiency syndrome and severe mental retardation (300352), Lion-Francois et al. (2006) identified a 395G-T transversion in the SLC6A8 gene, resulting in a gly132-to-val (G132V) substitution. The patient had delayed onset of walking and autistic behavior. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, CYS491TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs122453118,
|
|
|
|
|
|
gnomAD: rs122453118,
|
|
|
|
|
|
ClinVar: RCV000012470
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old boy with creatine deficiency syndrome and severe mental retardation (300352), Lion-Francois et al. (2006) identified a 1473C-G transversion in the SLC6A8 gene, resulting in a cys491-to-trp (C491W) substitution. The patient had delayed onset of walking, seizures, and autistic features. Brain imaging showed atrophy of the left caudate and hippocampus and a thin corpus callosum. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, 3-BP DEL, 1006AAC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs782433037,
|
|
|
|
|
|
|
|
ClinVar: RCV000012471, RCV000255812
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old boy with creatine deficiency syndrome (300352), Clark et al. (2006) identified a hemizygous 3-bp deletion (1006delAAC) in exon 6 of the SLC6A8 gene, resulting in a deletion of a highly conserved residue asn336. The patient had moderate mental retardation, attention deficit-hyperactivity disorder, microcephaly, and tall stature. </p><p>Battini et al. (2007) identified the 1006delAAC mutation in a 9.5-year-old Italian boy with mental retardation and verbal dyspraxia. He had delayed psychomotor development, hypotonia, seizures, and severe language deficit with oral-motor dyspraxia, irritability, and temper tantrums. Detailed language evaluation showed problems in picture naming and phonetics, whereas receptive vocabulary was less severely affected. Social interaction was good despite the severe expressive limitation. Battini et al. (2007) noted that the phenotype in their patient was different than that reported by Clark et al. (2006). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 CEREBRAL CREATINE DEFICIENCY SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC6A8, ARG278CYS
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV004799653
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a boy with creatine deficiency syndrome (CCDS1; 300352), Longo et al. (2024) identified hemizygosity for a c.832C-T transition in the SLC6A8 gene, resulting in an arg278-to-cys (R278C) substitution. The mutation was identified with sequencing of the SLC6A8 gene. The mutation was reported once (in this patient) in the gnomAD database at an allele frequency of 1/1096567. Creatine uptake in patient fibroblasts was 25% of normal activity and cerebral creatine was 20% of normal as measured on MRS. </p></div>
|
|
</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">
|
|
Abplanalp, J., Laczko, E., Philp, N. J., Neidhardt, J., Zuercher, J., Braun, P., Schorderet, D. F., Munier, F. L., Verrey, F., Berger, W., Camargo, S. M. R., Kloeckener-Gruissem, B.
|
|
<strong>The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter.</strong>
|
|
Hum. Molec. Genet. 22: 3218-3226, 2013.
|
|
|
|
|
|
[PubMed: 23578822]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddt175]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barnwell, L. F. S., Chaudhuri, G., Townsel, J. G.
|
|
<strong>Cloning and sequencing of a cDNA encoding a novel member of the human brain GABA/noradrenaline neurotransmitter transporter family.</strong>
|
|
Gene 159: 287-288, 1995.
|
|
|
|
|
|
[PubMed: 7622069]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0378-1119(95)00104-e]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Battini, R., Chilosi, A., Mei, D., Casarano, M., Alessandri, M. G., Leuzzi, V., Ferretti, G., Tosetti, M., Bianchi, M. C., Cioni, G.
|
|
<strong>Mental retardation and verbal dyspraxia in a new patient with de novo creatine transporter (SLC6A8) mutation.</strong>
|
|
Am. J. Med. Genet. 143A: 1771-1774, 2007.
|
|
|
|
|
|
[PubMed: 17603797]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31827]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bizzi, A., Bugiani, M., Salomons, G. S., Hunneman, D. H., Moroni, I., Estienne, M., Danesi, U., Jakobs, C., Uziel, G.
|
|
<strong>X-linked creatine deficiency syndrome: a novel mutation in creatine transporter gene SLC6A8.</strong>
|
|
Ann. Neurol. 52: 227-231, 2002.
|
|
|
|
|
|
[PubMed: 12210795]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.10246]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clark, A. J., Rosenberg, E. H., Almeida, L. S., Wood, T. C., Jakobs, C., Stevenson, R. E., Schwartz, C. E., Salomons, G. S.
|
|
<strong>X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology.</strong>
|
|
Hum. Genet. 119: 604-610, 2006.
|
|
|
|
|
|
[PubMed: 16738945]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-006-0162-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dai, W., Vinnakota, S., Qian, X., Kunze, D. L., Sarkar, H. K.
|
|
<strong>Molecular characterization of the human CRT-1 creatine transporter expressed in Xenopus oocytes.</strong>
|
|
Arch. Biochem. Biophys. 361: 75-84, 1999.
|
|
|
|
|
|
[PubMed: 9882430]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/abbi.1998.0959]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eichler, E. E., Lu, F., Shen, Y., Antonacci, R., Jurecic, V., Doggett, N. A., Moyzis, R. K., Baldini, A., Gibbs, R. A., Nelson, D. L.
|
|
<strong>Duplication of a gene-rich cluster between 16p11.1 and Xq28: a novel pericentromeric-directed mechanism for paralogous genome evolution.</strong>
|
|
Hum. Molec. Genet. 5: 899-912, 1996.
|
|
|
|
|
|
[PubMed: 8817324]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.7.899]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gregor, P., Nash, S. R., Caron, M. G., Seldin, M. F., Warren, S. T.
|
|
<strong>Assignment of the creatine transporter gene (SLC6A8) to human chromosome Xq28 telomeric to G6PD.</strong>
|
|
Genomics 25: 332-333, 1995.
|
|
|
|
|
|
[PubMed: 7774949]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(95)80155-f]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hahn, K. A., Salomons, G. S., Tackels-Horne, D., Wood, T. C., Taylor, H. A., Schroer, R. J., Lubs, H. A., Jakobs, C., Olson, R. L., Holden, K. R., Stevenson, R. E., Schwartz, C. E.
|
|
<strong>X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28.</strong>
|
|
Am. J. Hum. Genet. 70: 1349-1356, 2002.
|
|
|
|
|
|
[PubMed: 11898126]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/340092]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoglund, P. J., Adzic, D., Scicluna, S. J., Lindblom, J., Fredriksson, R.
|
|
<strong>The repertoire of solute carriers of family 6: identification of new human and rodent genes.</strong>
|
|
Biochem. Biophys. Res. Commun. 336: 175-189, 2005.
|
|
|
|
|
|
[PubMed: 16125675]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2005.08.048]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iyer, G. S., Krahe, R., Goodwin, L. A., Doggett, N. A., Siciliano, M. J., Funanage, V. L., Proujansky, R.
|
|
<strong>Identification of a testis-expressed creatine transporter gene at 16p11.2 and confirmation of the X-linked locus to Xq28.</strong>
|
|
Genomics 34: 143-146, 1996.
|
|
|
|
|
|
[PubMed: 8661037]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0254]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ji, L., Zhao, X., Zhang, B., Kang, L., Song, W., Zhao, B., Xie, W., Chen, L., Hu, X.
|
|
<strong>Slc6a8-mediated creatine uptake and accumulation reprogram macrophage polarization via regulating cytokine responses.</strong>
|
|
Immunity 51: 272-284, 2019.
|
|
|
|
|
|
[PubMed: 31399282]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.immuni.2019.06.007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Levin, M. D., Bianconi, S., Smith, A., Cawley, N. X., Do, A. D., Hammond, D., Grafstein, J. F., Thurm, A., Miller, J., Perreault, J., Noguchi, A., Springer, D., Kozel, B. A., Spurney, C. F., Wassif, C. A., Yu, Z.-X., Schulze, A., Porter, F. D., Hannah-Shmouni, F.
|
|
<strong>X-linked creatine transporter deficiency results in prolonged QTc and increased sudden death risk in humans and disease model.</strong>
|
|
Genet. Med. 23: 1864-1872, 2021.
|
|
|
|
|
|
[PubMed: 34050321]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41436-021-01224-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lion-Francois, L., Cheillan, D., Pitelet, G., Acquaviva-Bourdain, C., Bussy, G., Cotton, F., Guibaud, L., Gerard, D., Rivier, C., Vianey-Saban, C., Jakobs, C., Salomons, G. S., des Portes, V.
|
|
<strong>High frequency of creatine deficiency syndromes in patients with unexplained mental retardation.</strong>
|
|
Neurology 67: 1713-1714, 2006.
|
|
|
|
|
|
[PubMed: 17101918]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000239153.39710.81]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Longo, N., Voss, L. A., Frigeni, M., Balakrishnan, B., Pasquali, M.
|
|
<strong>Response to therapy of creatine transporter deficiency caused by a hypomorphic variant in SLC6A8.</strong>
|
|
Molec. Genet. Metab. 143: 108595, 2024.
|
|
|
|
|
|
[PubMed: 39418753]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2024.108595]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mandel, J. L.
|
|
<strong>Comparative frequency of fragile-X (FMR1) and creatine transporter (SLC6A8) mutations in X-linked mental retardation. (Letter)</strong>
|
|
Am. J. Hum. Genet. 75: 730-731, 2004.
|
|
|
|
|
|
[PubMed: 15338463]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/424821]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nash, S. R., Giros, B., Kingsmore, S. F., Rochelle, J. M., Suter, S. T., Gregor, P., Seldin, M. F., Caron, M. G.
|
|
<strong>Cloning, pharmacological characterization, and genomic localization of the human creatine transporter.</strong>
|
|
Receptors Channels 2: 165-174, 1994.
|
|
|
|
|
|
[PubMed: 7953292]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peral, M. J., Garcia-Delgado, M., Calonge, M. L., Duran, J. M., De La Horra, M. C., Wallimann, T., Speer, O., Ilundain, A. A.
|
|
<strong>Human, rat and chicken small intestinal Na(+)-Cl(-)-creatine transporter: functional, molecular characterization and localization.</strong>
|
|
J. Physiol. 545: 133-144, 2002.
|
|
|
|
|
|
[PubMed: 12433955]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1113/jphysiol.2002.026377]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rosenberg, E. H., Almeida, L. S., Kleefstra, T., deGrauw, R. S., Yntema, H. G., Bahi, N., Moraine, C., Ropers, H.-H., Fryns, J.-P., deGrauw, T. J., Jakobs, C., Salomons, G. S.
|
|
<strong>High prevalence of SLC6A8 deficiency in X-linked mental retardation.</strong>
|
|
Am. J. Hum. Genet. 75: 97-105, 2004.
|
|
|
|
|
|
[PubMed: 15154114]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/422102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Salomons, G. S., van Dooren, S. J. M., Verhoeven, N. M., Cecil, K. M., Ball, W. S., Degrauw, T. J., Jakobs, C.
|
|
<strong>X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome.</strong>
|
|
Am. J. Hum. Genet. 68: 1497-1500, 2001.
|
|
|
|
|
|
[PubMed: 11326334]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/320595]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sandoval, N., Bauer, D., Brenner, V., Coy, J. F., Drescher, B., Kioschis, P., Korn, B., Nyakatura, G., Poustka, A., Reichwald, K., Rosenthal, A., Platzer, M.
|
|
<strong>The genomic organization of a human creatine transporter (CRTR) gene located in Xq28.</strong>
|
|
Genomics 35: 383-385, 1996.
|
|
|
|
|
|
[PubMed: 8661155]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0373]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schiaffino, M. C., Bellini, C., Costabello, L., Caruso, U., Jakobs, C., Salomons, G. S., Bonioli, E.
|
|
<strong>X-linked creatine transporter deficiency: clinical description of a patient with a novel SLC6A8 gene mutation.</strong>
|
|
Neurogenetics 6: 165-168, 2005.
|
|
|
|
|
|
[PubMed: 16086185]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10048-005-0002-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schlattner, U., Mockli, N., Speer, O., Werner, S., Wallimann, T.
|
|
<strong>Creatine kinase and creatine transporter in normal, wounded, and diseased skin.</strong>
|
|
J. Invest. Derm. 118: 416-423, 2002.
|
|
|
|
|
|
[PubMed: 11874479]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.0022-202x.2001.01697.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shojaiefard, M., Christie, D. L., Lang, F.
|
|
<strong>Stimulation of the creatine kinase transporter SLC6A8 by the protein kinases SGK1 and SGK3.</strong>
|
|
Biochem. Biophys. Res. Commun. 334: 742-746, 2005.
|
|
|
|
|
|
[PubMed: 16036218]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2005.06.164]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Valayannopoulos, V., Boddaert, N., Chabli, A., Barbier, V., Desguerre, I., Philippe, A., Afenjar, A., Mazzuca, M., Cheillan, D., Munnich, A., de Keyzer, Y., Jakobs, C., Salomons, G. S., de Lonlay, P.
|
|
<strong>Treatment by oral creatine, L-arginine and L-glycine in six severely affected patients with creatine transporter defect.</strong>
|
|
J. Inherit. Metab. Dis. 35: 151-157, 2012.
|
|
|
|
|
|
[PubMed: 21660517]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10545-011-9358-9]
|
|
|
|
|
|
</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">
|
|
Hilary J. Vernon - updated : 12/06/2024<br>Ada Hamosh - updated : 09/17/2024<br>Bao Lige - updated : 01/06/2020<br>Patricia A. Hartz - updated : 2/9/2015<br>Ada Hamosh - updated : 11/25/2014<br>Cassandra L. Kniffin - updated : 9/3/2008<br>Patricia A. Hartz - updated : 5/2/2008<br>Cassandra L. Kniffin - updated : 2/7/2008<br>Patricia A. Hartz - updated : 12/17/2007<br>Cassandra L. Kniffin - updated : 8/28/2006<br>Matthew B. Gross - updated : 5/12/2006<br>Marla J. F. O'Neill - updated : 11/23/2005<br>Cassandra L. Kniffin - updated : 11/9/2005<br>Victor A. McKusick - updated : 9/14/2004<br>Victor A. McKusick - updated : 6/30/2004<br>Cassandra L. Kniffin - updated : 10/2/2002<br>Victor A. McKusick - updated : 5/17/2002<br>Victor A. McKusick - updated : 6/20/2001<br>Alan F. Scott - updated : 8/21/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 2/25/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 12/09/2024<br>carol : 12/06/2024<br>alopez : 09/17/2024<br>mgross : 01/06/2020<br>mgross : 02/09/2015<br>mgross : 2/9/2015<br>mcolton : 2/9/2015<br>alopez : 11/25/2014<br>carol : 7/17/2013<br>ckniffin : 7/16/2013<br>carol : 4/20/2009<br>wwang : 9/24/2008<br>ckniffin : 9/3/2008<br>mgross : 5/2/2008<br>wwang : 2/20/2008<br>ckniffin : 2/7/2008<br>mgross : 12/19/2007<br>terry : 12/17/2007<br>carol : 11/27/2006<br>wwang : 9/5/2006<br>ckniffin : 8/28/2006<br>mgross : 5/12/2006<br>wwang : 11/23/2005<br>wwang : 11/23/2005<br>wwang : 11/22/2005<br>ckniffin : 11/9/2005<br>tkritzer : 9/15/2004<br>terry : 9/14/2004<br>alopez : 7/7/2004<br>terry : 6/30/2004<br>terry : 11/22/2002<br>carol : 10/31/2002<br>tkritzer : 10/25/2002<br>tkritzer : 10/25/2002<br>ckniffin : 10/2/2002<br>alopez : 5/24/2002<br>terry : 5/17/2002<br>carol : 3/8/2002<br>terry : 3/8/2002<br>carol : 8/6/2001<br>mcapotos : 6/27/2001<br>mcapotos : 6/26/2001<br>mcapotos : 6/22/2001<br>terry : 6/20/2001<br>mark : 8/21/1996<br>marlene : 8/19/1996<br>terry : 6/5/1996<br>terry : 6/3/1996<br>terry : 5/16/1996<br>joanna : 2/26/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|