4324 lines
377 KiB
Text
4324 lines
377 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
|
|
|
|
- *605086 - TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 2; TREM2
|
|
|
|
|
|
- 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=605086"><span class="mim-navbar-menu-font"> Contact Us </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li>
|
|
|
|
<a href="/mimmatch/">
|
|
|
|
<span class="mim-navbar-menu-font">
|
|
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
|
|
MIMmatch
|
|
</span>
|
|
</span>
|
|
</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
|
|
<li>
|
|
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
|
|
</li>
|
|
<li>
|
|
<a href="/donors"> Donors </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
|
|
<li>
|
|
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/search"> Search Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/linking"> Linking Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/api"> API Help </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/external"> External Links </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/agreement"> Use Agreement </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/copyright"> Copyright </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimSearch" class="hidden-print">
|
|
|
|
<div class="container">
|
|
|
|
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
|
|
|
|
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
|
|
<input type="hidden" id="mimSearchStart" name="start" value="1" />
|
|
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
|
|
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
|
|
<div class="form-group">
|
|
<div class="input-group">
|
|
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
|
|
<div class="input-group-btn">
|
|
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
|
|
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
|
|
<ul class="dropdown-menu dropdown-menu-right">
|
|
<li class="dropdown-header">
|
|
Advanced Search
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/entry"> OMIM </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/geneMap"> Gene Map </a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/history"> Search History </a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
|
|
<span class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</form>
|
|
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
<!-- <div id="mimSearch"> -->
|
|
|
|
|
|
|
|
|
|
<div id="mimContent">
|
|
|
|
|
|
|
|
<div class="container hidden-print">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
|
|
<div id="mimAlertBanner">
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
|
|
|
|
<div id="mimFloatingTocMenu" class="small" role="navigation">
|
|
|
|
<p>
|
|
<span class="h4">*605086</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/605086">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=ENSG00000095970;t=ENST00000373113" 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=54209" 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=605086" 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=ENSG00000095970;t=ENST00000373113" 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_001271821,NM_018965" 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_018965" 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=605086" 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=05473&isoform_id=05473_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/TREM2" 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/7800157,9507203,17425162,21619572,50401689,77702076,119624437,119624438,119624439,189053356,312831501,425876764" 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/Q9NZC2" 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=54209" 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=ENSG00000095970;t=ENST00000373113" 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=TREM2" 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=TREM2" 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+54209" 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/TREM2" 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:54209" 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/54209" 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=chr6&hgg_gene=ENST00000373113.8&hgg_start=41158508&hgg_end=41163116&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://medlineplus.gov/genetics/gene/trem2" 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=605086[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=605086[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000095970" 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=TREM2" 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=TREM2" 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=TREM2" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=TREM2&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/PA38468" 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:17761" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:1913150" 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/TREM2#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:1913150" 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/54209/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=54209" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:54209" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=TREM2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
605086
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 2; TREM2
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=TREM2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TREM2</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/6/479?start=-3&limit=10&highlight=479">6p21.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:41158508-41163116&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'})">6:41,158,508-41,163,116</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=615080,618193" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/6/479?start=-3&limit=10&highlight=479">
|
|
6p21.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Alzhieimer disease 17, susceptibility to}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/615080"> 615080 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/618193"> 618193 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/605086" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/605086" 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 TREM2 gene encodes a type I transmembrane protein that is a member of the immunoglobulin (Ig) receptor superfamily. It contains an ectodomain, a transmembrane domain, and a short cytoplasmic tail. TREM2 is found on the surface of osteoclasts, immature dendritic cells, and macrophages. In the central nervous system, TREM2 is primarily expressed in microglia (summary by <a href="#2" class="mim-tip-reference" title="Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeek, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., Younkin, S., Das, P., Fryer, J. D., Bu, G. <strong>Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2).</strong> J. Biol. Chem. 290: 26043-26050, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26374899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26374899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26374899[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M115.679043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26374899">Atagi et al., 2015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26374899" 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>Monocyte/macrophage- and neutrophil-mediated inflammatory responses can be stimulated through a variety of receptors, including G protein-linked 7-transmembrane receptors (e.g., FPR1; <a href="/entry/136537">136537</a>), Fc receptors (see <a href="/entry/146790">146790</a>), CD14 (<a href="/entry/158120">158120</a>) and Toll-like receptors (e.g., TLR4; <a href="/entry/603030">603030</a>), and cytokine receptors (e.g., IFNGR1; <a href="/entry/107470">107470</a>). Engagement of these receptors can also prime myeloid cells to respond to other stimuli. Myeloid cells express receptors belonging to the Ig superfamily, such as TREM2, or to the C-type lectin superfamily. Depending on their transmembrane and cytoplasmic sequence structure, these receptors have either activating (e.g., KIR2DS1; <a href="/entry/604952">604952</a>) or inhibitory functions (e.g., KIR2DL1; <a href="/entry/604936">604936</a>). TREM2 is an activating receptor that is expressed on macrophages and dendritic cells (<a href="#5" class="mim-tip-reference" title="Bouchon, A., Dietrich, J., Colonna, M. <strong>Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes.</strong> J. Immun. 164: 4991-4995, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10799849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10799849</a>] [<a href="https://doi.org/10.4049/jimmunol.164.10.4991" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10799849">Bouchon et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10799849" 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>By searching an EST database with TREM1 (<a href="/entry/605085">605085</a>) as the probe, <a href="#5" class="mim-tip-reference" title="Bouchon, A., Dietrich, J., Colonna, M. <strong>Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes.</strong> J. Immun. 164: 4991-4995, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10799849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10799849</a>] [<a href="https://doi.org/10.4049/jimmunol.164.10.4991" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10799849">Bouchon et al. (2000)</a> identified a cDNA encoding TREM2. The predicted 230-amino acid TREM2 protein was expressed on macrophages and dendritic cells but not on granulocytes or monocytes, suggesting a role for TREM2 in chronic rather than acute inflammatory conditions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10799849" 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 flow cytometric analysis, <a href="#26" class="mim-tip-reference" title="Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., Colonna, M. <strong>Cutting edge: TREM-2 attenuates macrophage activation.</strong> J. Immun. 177: 3520-3524, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16951310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16951310</a>] [<a href="https://doi.org/10.4049/jimmunol.177.6.3520" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16951310">Turnbull et al. (2006)</a> demonstrated that murine Trem2 was expressed on macrophages recruited to peripheral tissues, but not on tissue-resident macrophages, circulating cells, or myeloid progenitors. Il4 (<a href="/entry/147780">147780</a>) induced expression of Trem2 on resident peritoneal cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16951310" 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>By genomic sequence analysis, <a href="#1" class="mim-tip-reference" title="Allcock, R. J. N., Barrow, A. D., Forbes, S., Beck, S., Trowsdale, J. <strong>The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44.</strong> Europ. J. Immun. 33: 567-577, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12645956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12645956</a>] [<a href="https://doi.org/10.1002/immu.200310033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12645956">Allcock et al. (2003)</a> determined that all genes in the TREM cluster have an exon encoding the 5-prime UTR and leader peptide, a second exon encoding the IgV domain, and a variable number of downstream exons encoding the stalk, transmembrane, and cytoplasmic regions. TREM2 contains 5 exons. A soluble splice variant of TREM2 lacks exon 4, which encodes the transmembrane region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12645956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By somatic cell hybrid analysis, <a href="#5" class="mim-tip-reference" title="Bouchon, A., Dietrich, J., Colonna, M. <strong>Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes.</strong> J. Immun. 164: 4991-4995, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10799849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10799849</a>] [<a href="https://doi.org/10.4049/jimmunol.164.10.4991" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10799849">Bouchon et al. (2000)</a> mapped the TREM1 and TREM2 genes to chromosome 6, where LY95 (<a href="/entry/604531">604531</a>) is located. By genomic sequence analysis, <a href="#1" class="mim-tip-reference" title="Allcock, R. J. N., Barrow, A. D., Forbes, S., Beck, S., Trowsdale, J. <strong>The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44.</strong> Europ. J. Immun. 33: 567-577, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12645956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12645956</a>] [<a href="https://doi.org/10.1002/immu.200310033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12645956">Allcock et al. (2003)</a> mapped the TREM2 gene to chromosome 6p21.1, within a TREM gene cluster. The mouse Trem2 gene maps to chromosome 17 in a region that shows homology of synteny to human chromosome 6. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10799849+12645956" 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>TREM2 forms a receptor signaling complex with TYROBP (<a href="/entry/604142">604142</a>) (<a href="#7" class="mim-tip-reference" title="Campbell, K. S., Colonna, M. <strong>DAP12: a key accessory protein for relaying signals by natural killer cell receptors.</strong> Int. J. Biochem. Cell Biol. 31: 631-636, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10404635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10404635</a>] [<a href="https://doi.org/10.1016/s1357-2725(99)00022-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10404635">Campbell and Colonna, 1999</a>; <a href="#6" class="mim-tip-reference" title="Bouchon, A., Hernandez-Munain, C., Cella, M., Colonna, M. <strong>A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells.</strong> J. Exp. Med. 194: 1111-1122, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11602640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11602640</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11602640[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/10.1084/jem.194.8.1111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11602640">Bouchon et al., 2001</a>) and triggers activation of the immune responses in macrophages and dendritic cells (<a href="#16" class="mim-tip-reference" title="Lanier, L. L., Bakker, A. B. H. <strong>The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function.</strong> Immun. Today 21: 611-614, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11114420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11114420</a>] [<a href="https://doi.org/10.1016/s0167-5699(00)01745-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11114420">Lanier and Bakker, 2000</a>). Patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), in whom mutations in the TYROBP (PLOSL1; <a href="/entry/221770">221770</a>) or TREM2 (PLOSL2; <a href="/entry/618193">618193</a>) genes have been identified, have no defects in cell-mediated immunity, suggesting a remarkable capacity of the human immune system to compensate for the inactive TYROBP-mediated activation pathway. The data of <a href="#21" class="mim-tip-reference" title="Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L. <strong>Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.</strong> Am. J. Hum. Genet. 71: 656-662, 2002. Note: Erratum: Am. J. Hum. Genet. 72: 225 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12080485[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/10.1086/342259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12080485">Paloneva et al. (2002)</a> suggested that the TYROBP-mediated signaling pathway plays a significant role in human brain and bone tissue and provide an interesting example of how mutations in 2 different subunits of a multisubunit receptor complex result in an identical human disease phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10404635+12080485+11602640+11114420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Paloneva, J., Mandelin, J., Kiialainen, A., Bohling, T., Prudlo, J., Hakola, P., Haltia, M., Konttinen, Y. T., Peltonen, L. <strong>DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features.</strong> J. Exp. Med. 198: 669-675, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12925681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12925681</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12925681[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/10.1084/jem.20030027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12925681">Paloneva et al. (2003)</a> analyzed differentiation of peripheral blood mononuclear cells from DAP12 (TYROBP)- and TREM2-deficient Finnish or German PLOSL patients into osteoclasts. They found that homozygous loss-of-function mutations in DAP12 or TREM2 resulted in inefficient, aberrant, and delayed differentiation into osteoclasts and significantly diminished bone resorption capability in vitro. RT-PCR analysis detected no differences between patient and control cells in the expression of several genes, but expression of DAP12 and TREM2 increased in control cells during osteoclastic differentiation. <a href="#20" class="mim-tip-reference" title="Paloneva, J., Mandelin, J., Kiialainen, A., Bohling, T., Prudlo, J., Hakola, P., Haltia, M., Konttinen, Y. T., Peltonen, L. <strong>DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features.</strong> J. Exp. Med. 198: 669-675, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12925681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12925681</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12925681[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/10.1084/jem.20030027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12925681">Paloneva et al. (2003)</a> concluded that the DAP12-TREM2 signaling complex is important in the differentiation and function of osteoclasts. Independently, <a href="#8" class="mim-tip-reference" title="Cella, M., Buonsanti, C., Strader, C., Kondo, T., Salmaggi, A., Colonna, M. <strong>Impaired differentiation of osteoclasts in TREM-2-deficient individuals.</strong> J. Exp. Med. 198: 645-651, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12913093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12913093</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12913093[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/10.1084/jem.20022220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12913093">Cella et al. (2003)</a> also showed that TREM2-deficient patients have impaired osteoclast differentiation and function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12925681+12913093" 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="Bailey, C. C., DeVaux, L. B., Farzan, M. <strong>The triggering receptor expressed on myeloid cells 2 binds apolipoprotein E.</strong> J. Biol. Chem. 290: 26033-26042, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26374897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26374897</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26374897[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M115.677286" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26374897">Bailey et al. (2015)</a> and <a href="#2" class="mim-tip-reference" title="Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeek, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., Younkin, S., Das, P., Fryer, J. D., Bu, G. <strong>Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2).</strong> J. Biol. Chem. 290: 26043-26050, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26374899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26374899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26374899[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M115.679043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26374899">Atagi et al. (2015)</a> independently identified ApoE (<a href="/entry/107741">107741</a>) and APOA1 (<a href="/entry/107680">107680</a>) as binding ligands for TREM2. In vitro studies showed that binding of APOE to TREM2 was associated with increased phagocytosis of apoE-bound apoptotic neurons by primary microglia in a manner that was dependent on TREM2 expression. Expression of the TREM2 variant R47H (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs75932628;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs75932628</a>) dramatically reduced the affinity of APOE for TREM2. The findings established a critical role for TREM2 in regulating the neuroinflammatory environment, and demonstrated a biochemical link between 2 proteins associated with the development of Alzheimer disease (see, e.g., AD17, <a href="/entry/615080">615080</a>). Furthermore, <a href="#3" class="mim-tip-reference" title="Bailey, C. C., DeVaux, L. B., Farzan, M. <strong>The triggering receptor expressed on myeloid cells 2 binds apolipoprotein E.</strong> J. Biol. Chem. 290: 26033-26042, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26374897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26374897</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26374897[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M115.677286" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26374897">Bailey et al. (2015)</a> suggested that the R47H variant may reduce the ability of TREM2+ phagocytes to bind APOE within senile plaques, thereby decreasing the clearance of beta-amyloid (APP; <a href="/entry/104760">104760</a>) from the brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26374897+26374899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Schlepckow, K., Kleinberger, G., Fukumori, A., Feederle, R., Lichtenthaler, S. F., Steiner, H., Haass, C. <strong>An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function.</strong> EMBO Molec. Med. 9: 1356-1365, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28855300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28855300</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28855300[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/10.15252/emmm.201707672" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28855300">Schlepckow et al. (2017)</a> determined that TREM2 is shed by proteases of the ADAM family C-terminal to histidine-157, a position where an Alzheimer disease-associated coding variant (H157Y) was discovered in the Han Chinese population (<a href="#12" class="mim-tip-reference" title="Jiang, T., Tan, L., Chen, Q., Tan, M.-S., Zhou, J.-S., Zhu, X.-C., Lu, H., Wang, H.-F., Zhang, Y.-D., Yu, J.-T. <strong>A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese.</strong> Neurobiol. Aging 42: 217.e1-217.e3, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27067662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27067662</a>] [<a href="https://doi.org/10.1016/j.neurobiolaging.2016.02.023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27067662">Jiang et al., 2016</a>). Unlike mutations in the Ig-like domain, the H157Y variant within the stalk region leads to enhanced shedding of TREM2. Elevated ectodomain shedding reduces cell surface full-length TREM2 and lowers TREM2-dependent phagocytosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27067662+28855300" 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 an unbiased protein microarray screen, <a href="#27" class="mim-tip-reference" title="Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., Sheng, M. <strong>TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid-beta by microglia.</strong> Neuron 91: 328-340, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27477018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27477018</a>] [<a href="https://doi.org/10.1016/j.neuron.2016.06.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27477018">Yeh et al. (2016)</a> identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ, <a href="/entry/185430">185430</a> and APOE) as ligands of TREM2. Binding of these ligands by TREM2 was abolished or reduced by Alzheimer disease-associated risk variants (see MOLECULAR GENETICS). Overexpression of wildtype TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells, while TREM2 carrying disease-associated variants was impaired in this activity. TREM2-knockout microglia showed reduced internalization of LDL and CLU. Beta-amyloid binds to lipoproteins, and this complex was taken up by microglia in a TREM2-dependent manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27477018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="biochemicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
<a href="#25" class="mim-tip-reference" title="Sudom, A., Talreja, S., Danao, J., Bragg, E., Kegel, R., Min, X., Richardson, J., Zhang, Z., Sharkov, N., Marcora, E., Thibault, S., Bradley, J., Wood, S., Lim, A.-C., Chen, H., Wang, S., Foltz, I. N., Sambashivan, S., Wang, Z. <strong>Molecular basis for the loss-of-function effects of the Alzheimer's disease-associated R47H variant of the immune receptor TREM2.</strong> J. Biol. Chem. 293: 12634-12646, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29794134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29794134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29794134[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.RA118.002352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29794134">Sudom et al. (2018)</a> reported 3 high-resolution structures for the extracellular ligand-binding domains of R47H mutant TREM2, apolipoprotein-bound wildtype, and phosphatidylserine-bound wildtype TREM2 at 1.8, 2.2, and 2.2 angstroms, respectively. The structures revealed that arg47 plays a critical role in maintaining the structural features of the complementarity-determining region-2 (CDR2) loop and the putative positive ligand-interacting surface (PLIS), stabilizing conformations capable of ligand interaction. <a href="#25" class="mim-tip-reference" title="Sudom, A., Talreja, S., Danao, J., Bragg, E., Kegel, R., Min, X., Richardson, J., Zhang, Z., Sharkov, N., Marcora, E., Thibault, S., Bradley, J., Wood, S., Lim, A.-C., Chen, H., Wang, S., Foltz, I. N., Sambashivan, S., Wang, Z. <strong>Molecular basis for the loss-of-function effects of the Alzheimer's disease-associated R47H variant of the immune receptor TREM2.</strong> J. Biol. Chem. 293: 12634-12646, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29794134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29794134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29794134[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.RA118.002352" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29794134">Sudom et al. (2018)</a> concluded that, together with in vitro and in vivo characterization, their structural findings elucidated the molecular mechanism underlying loss of ligand binding, putative oligomerization, and functional activity of R47H TREM2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29794134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2</em></strong></p><p>
|
|
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a globally distributed recessively inherited disorder leading to death during the fifth decade of life and is characterized by early-onset progressive dementia and bone cysts. Mutations in the TYROBP gene had been shown to cause the disorder (see PLOSL1; <a href="/entry/221770">221770</a>), but <a href="#21" class="mim-tip-reference" title="Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L. <strong>Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.</strong> Am. J. Hum. Genet. 71: 656-662, 2002. Note: Erratum: Am. J. Hum. Genet. 72: 225 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12080485[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/10.1086/342259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12080485">Paloneva et al. (2002)</a> found that some patients with PLOSL did not have mutations in the TYROBP gene. <a href="#21" class="mim-tip-reference" title="Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L. <strong>Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.</strong> Am. J. Hum. Genet. 71: 656-662, 2002. Note: Erratum: Am. J. Hum. Genet. 72: 225 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12080485[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/10.1086/342259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12080485">Paloneva et al. (2002)</a> studied the segregation of marker haplotypes flanking genes that encode polypeptides interacting with TYROBP. The only chromosomal region showing complete segregation to PLOSL was the 6p22-p21 region which includes the TREM2 gene. Mutations in this gene were identified in each of 2 affected families with PLOSL2 (<a href="/entry/618193">618193</a>), a Swedish and a Norwegian family, and subsequently in 3 other families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12080485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 6 patients with PLOSL2, including 2 sibs, <a href="#15" class="mim-tip-reference" title="Klunemann, H. H., Ridha, B. H., Magy, L., Wherrett, J. R., Hemelsoet, D. M., Keen, R. W., De Bleecker, J. L., Rossor, M. N., Marienhagen, J., Klein, H. E., Peltonen, L., Paloneva, J. <strong>The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2.</strong> Neurology 64: 1502-1507, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15883308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15883308</a>] [<a href="https://doi.org/10.1212/01.WNL.0000160304.00003.CA" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15883308">Klunemann et al. (2005)</a> identified 4 different homozygous mutations in the TREM2 gene (see, e.g., <a href="#0006">605086.0006</a> and <a href="#0007">605086.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15883308" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Susceptibility to Alzheimer Disease 17</em></strong></p><p>
|
|
In a genomewide association study of 3,550 Icelandic individuals with Alzheimer disease (AD17; <a href="/entry/615080">615080</a>) and a large number of controls, <a href="#14" class="mim-tip-reference" title="Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., Rujescu, D., Hampel, H., and 12 others. <strong>Variant of TREM2 associated with the risk of Alzheimer's disease.</strong> New Eng. J. Med. 368: 107-116, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23150908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23150908</a>] [<a href="https://doi.org/10.1056/NEJMoa1211103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23150908">Jonsson et al. (2013)</a> found a significant association between the T allele of an R47H (<a href="#0008">605086.0008</a>) variation in the TREM2 gene (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs75932628;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs75932628</a>) and risk of disease (odds ratio (OR) 2.92, p = 3.42 x 10(-10)). The association was stronger when the controls were older than 85 years. There were 4 homozygous carriers of the variant, 2 of whom were diagnosed with AD. The association was replicated among 2,037 AD cases and 9,727 controls (OR 2.83, p = 0.002). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23150908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an association study of 279 patients with late-onset AD and 346 controls, all from a Chinese southern Han population, <a href="#18" class="mim-tip-reference" title="Ma, J., Zhou, Y., Xu, J., Liu, X., Wang, Y., Deng, Y., Wang, G., Xu, W., Ren, R., Liu, X., Zhang, Y., Wang, C., Tang, H., Chen, S. <strong>Association study of TREM2 polymorphism rs75932628 with late-onset Alzheimer's disease in Chinese Han population.</strong> Neurol. Res. 36: 894-896, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24725293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24725293</a>] [<a href="https://doi.org/10.1179/1743132814Y.0000000376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24725293">Ma et al. (2014)</a> failed to detect the <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs75932628;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs75932628</a>T variant. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24725293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By high-throughput sequencing of the TREM2 gene in 988 late-onset AD patients and 1,354 healthy controls, all of Han Chinese origin, <a href="#12" class="mim-tip-reference" title="Jiang, T., Tan, L., Chen, Q., Tan, M.-S., Zhou, J.-S., Zhu, X.-C., Lu, H., Wang, H.-F., Zhang, Y.-D., Yu, J.-T. <strong>A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese.</strong> Neurobiol. Aging 42: 217.e1-217.e3, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27067662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27067662</a>] [<a href="https://doi.org/10.1016/j.neurobiolaging.2016.02.023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27067662">Jiang et al. (2016)</a> identified 4 rare coding variants and showed that one of these, H157Y (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs22342555;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs22342555</a>), conferred risk of AD in their cohort. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27067662" 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="#23" class="mim-tip-reference" title="Song, W., Hooli, B., Mullin, K., Jin, S. C., Cella, M., Ulland, T. K., Wang, Y., Tanzi, R. E., Colonna, M. <strong>Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation.</strong> Alzheimers Dement. 13: 381-387, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27520774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27520774</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27520774[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.jalz.2016.07.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27520774">Song et al. (2017)</a> analyzed the AD risk of several TREM2 variants, compared each variant's risk and functional impact by reporter assay, and analyzed expression of TREM2 in human monocytes. Risk analysis was carried out in 1,376 participants (941 affected, 404 unaffected, 31 not determined) from 410 families from the National Institutes of Mental Health (NIMH) Alzheimer's Disease Genetics Initiative Study, and in 10,449 Caucasian cases and controls from the Alzheimer's Disease Sequencing Project (ADSP). The R47H variant had a profound negative effect on signaling in response to most tested lipid ligands, and H157Y demonstrated a lesser defect. Family-based association analysis in the NIMH AD families yielded a p value of .004 for R47H. The H157Y variant was found in 5 of 8 affected individuals and in no unaffected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27520774" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study using pooled sequencing of 2,082 AD cases and 1,648 cognitively normal elderly controls of European American descent, <a href="#13" class="mim-tip-reference" title="Jin, S. C., Benitez, B. A., Karch, C. M., Cooper, B., Skorupa, T., Carrell, D., Norton, J. B., Hsu, S., Harari, O., Cai, Y., Bertelsen, S., Goate, A. M., Cruchaga, C. <strong>Coding variants in TREM2 increase risk for Alzheimer's disease.</strong> Hum. Molec. Genet. 23: 5838-5846, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24899047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24899047</a>] [<a href="https://doi.org/10.1093/hmg/ddu277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24899047">Jin et al. (2014)</a> identified 16 nonsynonymous variants in the TREM2 gene, of which 2 were significantly associated with disease risk in single variant analysis: R47H (odds ratio (OR) 2.63, p = 0.000917) and R62H (<a href="#0009">605086.0009</a>) (OR 2.36, p = 0.000236). Additional variants were likely also to confer risk, as the association was still highly significant even after excluding R47H (OR 2.47, p = 0.000000537). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24899047" 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="#17" class="mim-tip-reference" title="Li, R., Wang, X., He, P. <strong>The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta-analysis.</strong> Exp. Ther. Med. 21: 347, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33732320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33732320</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33732320[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/10.3892/etm.2021.9778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33732320">Li et al. (2021)</a> performed a metaanalysis of 26 datasets comprising 28,007 AD cases and 45,121 controls. A significantly increased risk of AD was observed in R47H carriers versus noncarriers (OR 3.88, 95% CI, 3.17-4.76, p less than 0.001), R62H (OR 1.37, 95% CI, 1.11-1.70, p = 0.004), and H157Y (OR 4.22, 95% CI, 1.93-9.21, p less than 0.001). All of these variants are present primarily in individuals of European descent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33732320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a metaanalysis of 24,808 Alzheimer disease patients and 1,165,514 controls to examine the role of missense variants in TREM2, <a href="#24" class="mim-tip-reference" title="Stefansson, H., Walters, G. B., Sveinbjornsson, G., Tragante, V., Einarsson, G., Helgason, H., Sigurdsson, A., Beyter, D., Snaebjarnarson, A. S., Ivarsdottir, E. V., Thorleifsson, G., Halldorsson, B. V., and 58 others. <strong>Homozygosity for R47H in TREM2 and the risk of Alzheimer's disease.</strong> New Eng. J. Med. 390: 2217-2219, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38899702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38899702</a>] [<a href="https://doi.org/10.1056/NEJMc2314334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38899702">Stefansson et al. (2024)</a> identified R47H as having an incomplete recessive effect (homozygotes for this variant are at a much greater risk of AD than heterozygotes). Individuals who were compound heterozygous for the R47H and R62H alleles had a higher risk of earlier onset of AD than heterozygotes for either, but much less risk than R47H homozygotes. <a href="#24" class="mim-tip-reference" title="Stefansson, H., Walters, G. B., Sveinbjornsson, G., Tragante, V., Einarsson, G., Helgason, H., Sigurdsson, A., Beyter, D., Snaebjarnarson, A. S., Ivarsdottir, E. V., Thorleifsson, G., Halldorsson, B. V., and 58 others. <strong>Homozygosity for R47H in TREM2 and the risk of Alzheimer's disease.</strong> New Eng. J. Med. 390: 2217-2219, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38899702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38899702</a>] [<a href="https://doi.org/10.1056/NEJMc2314334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38899702">Stefansson et al. (2024)</a> noted that R47H homozygosity does not contribute to amyloid-beta overproduction but instead disrupts amyloid-beta clearance, leading to the accumulation of amyloid plaques. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38899702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#26" class="mim-tip-reference" title="Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., Colonna, M. <strong>Cutting edge: TREM-2 attenuates macrophage activation.</strong> J. Immun. 177: 3520-3524, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16951310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16951310</a>] [<a href="https://doi.org/10.4049/jimmunol.177.6.3520" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16951310">Turnbull et al. (2006)</a> found that mice lacking Trem2 were unable to inhibit cytokine production in response to microbial products. There was no difference in cytokine production by macrophages from Trem2-deficient mice and Dap12-deficient mice, leading <a href="#26" class="mim-tip-reference" title="Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., Colonna, M. <strong>Cutting edge: TREM-2 attenuates macrophage activation.</strong> J. Immun. 177: 3520-3524, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16951310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16951310</a>] [<a href="https://doi.org/10.4049/jimmunol.177.6.3520" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16951310">Turnbull et al. (2006)</a> to conclude that Trem2 is the receptor operative in the increased macrophage cytokine production observed in Dap12-deficient cells. They concluded that TREM2 expressed on newly differentiated and alternatively activated macrophages functions to restrain macrophage activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16951310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majournie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., Hazrati, L., Collinge, J., and 12 others. <strong>TREM2 variants in Alzheimer's disease.</strong> New Eng. J. Med. 368: 117-127, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23150934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23150934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23150934[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/10.1056/NEJMoa1211851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23150934">Guerreiro et al. (2013)</a> showed that expression of Trem2 rose in parallel with a rise in cortical levels of beta-amyloid in the TgCRND8 mouse model of Alzheimer disease (AD; <a href="/entry/104300">104300</a>). The dysregulation of expression induced by beta-amyloid (A-beta; see <a href="/entry/104760">104760</a>) was relatively specific to Trem2, as its partner Tyrobp was not dysregulated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23150934" 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 immunohistochemistry, confocal microscopy, RT-PCR, and Western blot analyses, <a href="#11" class="mim-tip-reference" title="Jay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., Cotleur, A. C., Butovsky, O., Bekris, L., Staugaitis, S. M., Leverenz, J. B., Pimplikar, S. W., Landreth, G. E., Howell, G. R., Ransohoff, R. M., Lamb, B. T. <strong>TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer's disease mouse models.</strong> J. Exp. Med. 212: 287-295, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25732305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25732305</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25732305[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/10.1084/jem.20142322" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25732305">Jay et al. (2015)</a> demonstrated increased expression of Trem2 in Iba1 (AIF1; <a href="/entry/601833">601833</a>)-positive myeloid cells surrounding age-related A-beta plaque deposits in brains of 2 transgenic mouse models of AD. Similar expression patterns were observed in 2 neuropathologically confirmed human AD cases. Flow cytometric analysis showed that Trem2-positive macrophages surrounding A-beta deposits in transgenic mouse AD models expressed high levels of Cd45 (<a href="/entry/151460">151460</a>), a marker for peripherally derived macrophages. Transgenic AD mice lacking Trem2 had reduced A-beta plaque-associated macrophages, inflammation, hippocampal A-beta deposition, astrocytosis, and tau (MAPT; <a href="/entry/157140">157140</a>) pathology. <a href="#11" class="mim-tip-reference" title="Jay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., Cotleur, A. C., Butovsky, O., Bekris, L., Staugaitis, S. M., Leverenz, J. B., Pimplikar, S. W., Landreth, G. E., Howell, G. R., Ransohoff, R. M., Lamb, B. T. <strong>TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer's disease mouse models.</strong> J. Exp. Med. 212: 287-295, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25732305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25732305</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25732305[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/10.1084/jem.20142322" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25732305">Jay et al. (2015)</a> proposed that TREM2 has a role in AD pathology and in neuroinflammation in other central nervous system pathologies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25732305" 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="Filipello, F., Morini, R., Corradini, I., Zerbi, V., Canzi, A., Michalski, B., Erreni, M., Markicevic, M., Starvaggi-Cucuzza, C., Otero, K., Piccio, L., Cignarella, F., and 9 others. <strong>The microglial innate immune receptor TREM2 is required for synapse elimination and normal brain connectivity.</strong> Immunity 48: 979-991, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29752066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29752066</a>] [<a href="https://doi.org/10.1016/j.immuni.2018.04.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29752066">Filipello et al. (2018)</a> found that Trem2 was selectively expressed by microglial cells in both cortex and hippocampus at different stages of neuronal development in mice. Trem2 -/- mice had fewer microglial cells than wildtype, and the cells became less activated in hippocampus during the early stages of brain development. Whole-cell recording of miniature excitatory postsynaptic currents (mEPSCs) in pyramidal neurons of acute brain slices showed that Trem2 deficiency caused enhanced pre- and postsynaptic contacts and increased electrophysiologic activity. Trem2 -/- microglial cells lacked synapse elimination that occurred through a process requiring cell-to-cell contact. Measurement of engulfment capacity with microglial cells from primary cell culture revealed that Trem2 -/- microglial cells displayed significantly reduced engulfment of synaptosomes compared with wildtype, confirming the role of Trem2 in synapse elimination during brain development. Absence of Trem2 in mice did not compromise the anatomic connections between brain regions, but rather it impaired function, as Trem2 -/- mice displayed an underconnectivity phenotype between prefrontal and hippocampal regions. Trem2 -/- mice exhibited a strong increase in self-grooming and were defective in social behavior. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29752066" 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 Trem2 -/- mice subjected to a demyelinating cuprizone (CPZ) diet, <a href="#19" class="mim-tip-reference" title="Nugent, A. A., Lin, K., van Lengerich, B., Lianoglou, S., Przbyla, L., Davis, S. S., Llapashtica, C., Wang, J., Kim, D. J., Xia, D., Lucas, A., Baskaran, S., and 18 others. <strong>TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge.</strong> Neuron 105: 837-854, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31902528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31902528</a>] [<a href="https://doi.org/10.1016/j.neuron.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31902528">Nugent et al. (2020)</a> found that Trem2 deficiency prevented conversion from a homeostatic to a disease-associated microglia (DAM) state. Microglia from CPZ-challenged Trem2 -/- mice failed to upregulate lipid metabolism genes. Gene expression changes in microglia from CPZ-challenged Trem2 -/- mice were also present in aged Trem2 -/- microglia and were homogeneous across microglia, leading to neuronal damage during chronic demyelination. Chronic demyelination caused a profound alteration of cholesterol metabolism selectively in Trem2 -/- central nervous system, resulting in accumulated cholesteryl ester (CE) derived from myelin cholesterol in Trem2 -/- brain. This CE accumulation was because Trem2 -/- microglia were able to phagocytose myelin debris during demyelination but were unable to properly metabolize or mediate efflux of myelin lipids. Similar to Trem2 deficiency, Apoe deficiency caused microglial CE accumulation with CPZ. However, Apoe deficiency more broadly affected cholesterol metabolism in brain, as accumulation of CE also occurred in forebrain, glial cells, and cerebral spinal fluid. In vitro analysis showed that Trem2 bound myelin lipids and promoted downstream signaling, and as a result, myelin phagocytosis was impaired in Trem2 -/- cells. Analysis with myelin-treated Trem2-deficient mouse macrophages and human iPSC-derived microglia further revealed that CE accumulation was rescued by ACAT1 (<a href="/entry/607809">607809</a>) inhibitor and LXR agonist. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31902528" 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>9 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/605086" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=605086[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 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TREM2, TRP78TER
|
|
</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> rs104893998 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893998;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/rs104893998?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=rs104893998" 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=rs104893998" 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=RCV000005523 OR RCV000721925" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005523, RCV000721925" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005523...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Swedish families, <a href="#21" class="mim-tip-reference" title="Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L. <strong>Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.</strong> Am. J. Hum. Genet. 71: 656-662, 2002. Note: Erratum: Am. J. Hum. Genet. 72: 225 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12080485[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/10.1086/342259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12080485">Paloneva et al. (2002)</a> found that members with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; <a href="/entry/618193">618193</a>) had a homozygous G-to-A transition at position 233 of the TREM2 gene, changing tryptophan-78 to a translation termination codon (W78X). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12080485" 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 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TREM2, LYS186ASN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937876 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937876;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=rs28937876" 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=rs28937876" 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=RCV000005524" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005524" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005524</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Norwegian family, <a href="#21" class="mim-tip-reference" title="Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L. <strong>Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.</strong> Am. J. Hum. Genet. 71: 656-662, 2002. Note: Erratum: Am. J. Hum. Genet. 72: 225 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12080485[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/10.1086/342259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12080485">Paloneva et al. (2002)</a> found that members with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; <a href="/entry/618193">618193</a>) had a homozygous 558G-T change in the TREM2 gene, resulting in a lys186-to-asn (K186N) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12080485" 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 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TREM2, ASP134GLY
|
|
</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> rs28939079 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939079;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/rs28939079?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=rs28939079" 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=rs28939079" 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=RCV000005525" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005525" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005525</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an American family that originated from Slovakia that was reported to have polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; <a href="/entry/618193">618193</a>) by <a href="#4" class="mim-tip-reference" title="Bird, T. D., Koerker, R. M., Leaird, B. J., Vlcek, B. W., Thorning, D. R. <strong>Lipomembranous polycystic osteodysplasia (brain, bone, and fat disease): a genetic cause of presenile dementia.</strong> Neurology 33: 81-86, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6681564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6681564</a>] [<a href="https://doi.org/10.1212/wnl.33.1.81" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6681564">Bird et al. (1983)</a>, <a href="#21" class="mim-tip-reference" title="Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L. <strong>Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.</strong> Am. J. Hum. Genet. 71: 656-662, 2002. Note: Erratum: Am. J. Hum. Genet. 72: 225 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12080485[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/10.1086/342259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12080485">Paloneva et al. (2002)</a> identified homozygosity for a 401A-G substitution in the TREM2 gene, resulting in an asp134-to-gly (D134G) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6681564+12080485" 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 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TREM2, IVS3DS, T-C, +2
|
|
</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> rs386834144 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs386834144;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/rs386834144?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=rs386834144" 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=rs386834144" 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=RCV000050138 OR RCV001810417" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000050138, RCV001810417" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000050138...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Italian sibs with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; <a href="/entry/618193">618193</a>), <a href="#21" class="mim-tip-reference" title="Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L. <strong>Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.</strong> Am. J. Hum. Genet. 71: 656-662, 2002. Note: Erratum: Am. J. Hum. Genet. 72: 225 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12080485[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/10.1086/342259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12080485">Paloneva et al. (2002)</a> identified a homozygous mutation in the splice donor consensus site at the second position of exon 3 (482+2T-C) in the TREM2 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12080485" 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 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TREM2, TRP44TER
|
|
</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> rs104894001 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894001;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/rs104894001?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=rs104894001" 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=rs104894001" 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=RCV000005527" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005527" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005527</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Bolivian patient with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; <a href="/entry/618193">618193</a>), <a href="#21" class="mim-tip-reference" title="Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L. <strong>Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.</strong> Am. J. Hum. Genet. 71: 656-662, 2002. Note: Erratum: Am. J. Hum. Genet. 72: 225 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12080485[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/10.1086/342259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12080485">Paloneva et al. (2002)</a> identified a homozygous 132G-A mutation in the TREM2 gene, resulting in a trp44-to-ter (W44X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12080485" 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 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TREM2, VAL126GLY
|
|
</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> rs121908402 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908402;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/rs121908402?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=rs121908402" 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=rs121908402" 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=RCV000005528 OR RCV000721926 OR RCV003398447" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005528, RCV000721926, RCV003398447" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005528...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; <a href="/entry/618193">618193</a>), <a href="#15" class="mim-tip-reference" title="Klunemann, H. H., Ridha, B. H., Magy, L., Wherrett, J. R., Hemelsoet, D. M., Keen, R. W., De Bleecker, J. L., Rossor, M. N., Marienhagen, J., Klein, H. E., Peltonen, L., Paloneva, J. <strong>The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2.</strong> Neurology 64: 1502-1507, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15883308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15883308</a>] [<a href="https://doi.org/10.1212/01.WNL.0000160304.00003.CA" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15883308">Klunemann et al. (2005)</a> identified a homozygous 377T-G transversion in exon 2 of the TREM2 gene, resulting in a val126-to-gly (V126G) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15883308" 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 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TREM2, GLN33TER
|
|
</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> rs104894002 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894002;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/rs104894002?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=rs104894002" 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=rs104894002" 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=RCV000005529 OR RCV000721927 OR RCV002512810 OR RCV004018565 OR RCV005089179" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005529, RCV000721927, RCV002512810, RCV004018565, RCV005089179" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005529...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Belgian sibs with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; <a href="/entry/618193">618193</a>), <a href="#15" class="mim-tip-reference" title="Klunemann, H. H., Ridha, B. H., Magy, L., Wherrett, J. R., Hemelsoet, D. M., Keen, R. W., De Bleecker, J. L., Rossor, M. N., Marienhagen, J., Klein, H. E., Peltonen, L., Paloneva, J. <strong>The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2.</strong> Neurology 64: 1502-1507, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15883308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15883308</a>] [<a href="https://doi.org/10.1212/01.WNL.0000160304.00003.CA" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15883308">Klunemann et al. (2005)</a> identified a homozygous 97C-T transition in exon 2 of the TREM2 gene, resulting in a gln33-to-ter (Q33X) substitution and premature termination of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15883308" 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 ALZHEIMER DISEASE 17, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TREM2, ARG47HIS (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs75932628;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs75932628</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004731677" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004731677" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004731677</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By whole-genome analysis of 2,261 Icelandic individuals followed by imputation in 3,550 Alzheimer disease patients and over 100,000 controls, <a href="#14" class="mim-tip-reference" title="Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., Rujescu, D., Hampel, H., and 12 others. <strong>Variant of TREM2 associated with the risk of Alzheimer's disease.</strong> New Eng. J. Med. 368: 107-116, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23150908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23150908</a>] [<a href="https://doi.org/10.1056/NEJMoa1211103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23150908">Jonsson et al. (2013)</a> identified a SNP in the TREM2 gene, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs75932628;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs75932628</a>, as significantly associated with Alzheimer disease. The T allele of <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs75932628;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs75932628</a>, which encodes an arg47-to-his (R47H) substitution, was found to confer a significant risk of Alzheimer disease in Iceland (OR 2.92, 95% CI, 2.09-4.09, p = 3.42 x 10(-10)). The allele frequency of <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs75932628;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs75932628</a>-T in cognitively intact controls 85 years of age or older (0.46%) was significant less than in controls under age 85 years (0.64%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23150908" 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="Stefansson, H., Walters, G. B., Sveinbjornsson, G., Tragante, V., Einarsson, G., Helgason, H., Sigurdsson, A., Beyter, D., Snaebjarnarson, A. S., Ivarsdottir, E. V., Thorleifsson, G., Halldorsson, B. V., and 58 others. <strong>Homozygosity for R47H in TREM2 and the risk of Alzheimer's disease.</strong> New Eng. J. Med. 390: 2217-2219, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38899702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38899702</a>] [<a href="https://doi.org/10.1056/NEJMc2314334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38899702">Stefansson et al. (2024)</a> reported that the allele frequency of the R47H variant ranges from nearly absent (in non-Europeans) to 0.7% among Icelanders and 1.4% among Ashkenazi Jews. In a metaanalysis of 24,808 Alzheimer disease patients and 1,165,514 controls examining the role of missense variants in the TREM2, <a href="#24" class="mim-tip-reference" title="Stefansson, H., Walters, G. B., Sveinbjornsson, G., Tragante, V., Einarsson, G., Helgason, H., Sigurdsson, A., Beyter, D., Snaebjarnarson, A. S., Ivarsdottir, E. V., Thorleifsson, G., Halldorsson, B. V., and 58 others. <strong>Homozygosity for R47H in TREM2 and the risk of Alzheimer's disease.</strong> New Eng. J. Med. 390: 2217-2219, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38899702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38899702</a>] [<a href="https://doi.org/10.1056/NEJMc2314334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38899702">Stefansson et al. (2024)</a> identified R47H as having an incomplete recessive effect (homozygotes for this variant are at a much greater risk of AD than heterozygotes). Homozygotes for R47H had a high risk (OR 97.1, 95% CI, 23.5-401.1) of developing Alzheimer disease, and at an earlier age than homozygotes for the APOE4 allele (see AD2, <a href="/entry/104310">104310</a>). Individuals who were compound heterozygous for the R47H and R62H (<a href="/entry/605085#0009">605085.0009</a>) alleles had a higher risk of earlier onset of AD than heterozygotes for either, but much less risk than R47H homozygotes. Mean age of onset was 6.4 years earlier among R47H homozygotes than other genotypes in the study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38899702" 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 ALZHEIMER DISEASE 17, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TREM2, ARG62HIS (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs143332484;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs143332484</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004731676" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004731676" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004731676</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a study using pooled sequencing of 2,082 AD cases and 1,648 cognitively normal elderly controls of European American descent, <a href="#13" class="mim-tip-reference" title="Jin, S. C., Benitez, B. A., Karch, C. M., Cooper, B., Skorupa, T., Carrell, D., Norton, J. B., Hsu, S., Harari, O., Cai, Y., Bertelsen, S., Goate, A. M., Cruchaga, C. <strong>Coding variants in TREM2 increase risk for Alzheimer's disease.</strong> Hum. Molec. Genet. 23: 5838-5846, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24899047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24899047</a>] [<a href="https://doi.org/10.1093/hmg/ddu277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24899047">Jin et al. (2014)</a> identified the R62H variant in TREM2 as significantly associated with disease risk in single variant analysis (OR 2.36, p = 0.000236). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24899047" 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="Stefansson, H., Walters, G. B., Sveinbjornsson, G., Tragante, V., Einarsson, G., Helgason, H., Sigurdsson, A., Beyter, D., Snaebjarnarson, A. S., Ivarsdottir, E. V., Thorleifsson, G., Halldorsson, B. V., and 58 others. <strong>Homozygosity for R47H in TREM2 and the risk of Alzheimer's disease.</strong> New Eng. J. Med. 390: 2217-2219, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38899702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38899702</a>] [<a href="https://doi.org/10.1056/NEJMc2314334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38899702">Stefansson et al. (2024)</a> reported that the R62H allele confers a minor increased risk of AD in individuals from Iceland, compared with the R47H (<a href="/entry/605085#0008">605085.0008</a>) allele. Compound heterozygotes for these 2 variants had an earlier age of onset of AD than heterozygotes for either, but still were at much lower risk than R47H homozygotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38899702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Allcock2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Allcock, R. J. N., Barrow, A. D., Forbes, S., Beck, S., Trowsdale, J.
|
|
<strong>The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44.</strong>
|
|
Europ. J. Immun. 33: 567-577, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12645956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12645956</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12645956" 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/immu.200310033" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Atagi2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeek, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., Younkin, S., Das, P., Fryer, J. D., Bu, G.
|
|
<strong>Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2).</strong>
|
|
J. Biol. Chem. 290: 26043-26050, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26374899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26374899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26374899[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=26374899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M115.679043" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Bailey2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bailey, C. C., DeVaux, L. B., Farzan, M.
|
|
<strong>The triggering receptor expressed on myeloid cells 2 binds apolipoprotein E.</strong>
|
|
J. Biol. Chem. 290: 26033-26042, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26374897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26374897</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26374897[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=26374897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M115.677286" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Bird1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bird, T. D., Koerker, R. M., Leaird, B. J., Vlcek, B. W., Thorning, D. R.
|
|
<strong>Lipomembranous polycystic osteodysplasia (brain, bone, and fat disease): a genetic cause of presenile dementia.</strong>
|
|
Neurology 33: 81-86, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6681564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6681564</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6681564" 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/wnl.33.1.81" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Bouchon2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bouchon, A., Dietrich, J., Colonna, M.
|
|
<strong>Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes.</strong>
|
|
J. Immun. 164: 4991-4995, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10799849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10799849</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10799849" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.4049/jimmunol.164.10.4991" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Bouchon2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bouchon, A., Hernandez-Munain, C., Cella, M., Colonna, M.
|
|
<strong>A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells.</strong>
|
|
J. Exp. Med. 194: 1111-1122, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11602640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11602640</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11602640[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=11602640" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.194.8.1111" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Campbell1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Campbell, K. S., Colonna, M.
|
|
<strong>DAP12: a key accessory protein for relaying signals by natural killer cell receptors.</strong>
|
|
Int. J. Biochem. Cell Biol. 31: 631-636, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10404635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10404635</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10404635" 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/s1357-2725(99)00022-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Cella2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cella, M., Buonsanti, C., Strader, C., Kondo, T., Salmaggi, A., Colonna, M.
|
|
<strong>Impaired differentiation of osteoclasts in TREM-2-deficient individuals.</strong>
|
|
J. Exp. Med. 198: 645-651, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12913093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12913093</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12913093[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=12913093" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.20022220" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Filipello2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Filipello, F., Morini, R., Corradini, I., Zerbi, V., Canzi, A., Michalski, B., Erreni, M., Markicevic, M., Starvaggi-Cucuzza, C., Otero, K., Piccio, L., Cignarella, F., and 9 others.
|
|
<strong>The microglial innate immune receptor TREM2 is required for synapse elimination and normal brain connectivity.</strong>
|
|
Immunity 48: 979-991, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29752066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29752066</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29752066" 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.2018.04.016" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Guerreiro2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majournie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., Hazrati, L., Collinge, J., and 12 others.
|
|
<strong>TREM2 variants in Alzheimer's disease.</strong>
|
|
New Eng. J. Med. 368: 117-127, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23150934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23150934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23150934[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=23150934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa1211851" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Jay2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., Cotleur, A. C., Butovsky, O., Bekris, L., Staugaitis, S. M., Leverenz, J. B., Pimplikar, S. W., Landreth, G. E., Howell, G. R., Ransohoff, R. M., Lamb, B. T.
|
|
<strong>TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer's disease mouse models.</strong>
|
|
J. Exp. Med. 212: 287-295, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25732305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25732305</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25732305[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=25732305" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.20142322" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Jiang2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jiang, T., Tan, L., Chen, Q., Tan, M.-S., Zhou, J.-S., Zhu, X.-C., Lu, H., Wang, H.-F., Zhang, Y.-D., Yu, J.-T.
|
|
<strong>A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese.</strong>
|
|
Neurobiol. Aging 42: 217.e1-217.e3, 2016. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27067662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27067662</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27067662" 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.neurobiolaging.2016.02.023" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Jin2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jin, S. C., Benitez, B. A., Karch, C. M., Cooper, B., Skorupa, T., Carrell, D., Norton, J. B., Hsu, S., Harari, O., Cai, Y., Bertelsen, S., Goate, A. M., Cruchaga, C.
|
|
<strong>Coding variants in TREM2 increase risk for Alzheimer's disease.</strong>
|
|
Hum. Molec. Genet. 23: 5838-5846, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24899047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24899047</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24899047" 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/ddu277" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Jonsson2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., Rujescu, D., Hampel, H., and 12 others.
|
|
<strong>Variant of TREM2 associated with the risk of Alzheimer's disease.</strong>
|
|
New Eng. J. Med. 368: 107-116, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23150908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23150908</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23150908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa1211103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Klunemann2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Klunemann, H. H., Ridha, B. H., Magy, L., Wherrett, J. R., Hemelsoet, D. M., Keen, R. W., De Bleecker, J. L., Rossor, M. N., Marienhagen, J., Klein, H. E., Peltonen, L., Paloneva, J.
|
|
<strong>The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2.</strong>
|
|
Neurology 64: 1502-1507, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15883308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15883308</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15883308" 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.0000160304.00003.CA" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Lanier2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lanier, L. L., Bakker, A. B. H.
|
|
<strong>The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function.</strong>
|
|
Immun. Today 21: 611-614, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11114420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11114420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11114420" 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/s0167-5699(00)01745-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Li2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, R., Wang, X., He, P.
|
|
<strong>The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta-analysis.</strong>
|
|
Exp. Ther. Med. 21: 347, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33732320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33732320</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33732320[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=33732320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3892/etm.2021.9778" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Ma2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ma, J., Zhou, Y., Xu, J., Liu, X., Wang, Y., Deng, Y., Wang, G., Xu, W., Ren, R., Liu, X., Zhang, Y., Wang, C., Tang, H., Chen, S.
|
|
<strong>Association study of TREM2 polymorphism rs75932628 with late-onset Alzheimer's disease in Chinese Han population.</strong>
|
|
Neurol. Res. 36: 894-896, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24725293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24725293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24725293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1179/1743132814Y.0000000376" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Nugent2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nugent, A. A., Lin, K., van Lengerich, B., Lianoglou, S., Przbyla, L., Davis, S. S., Llapashtica, C., Wang, J., Kim, D. J., Xia, D., Lucas, A., Baskaran, S., and 18 others.
|
|
<strong>TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge.</strong>
|
|
Neuron 105: 837-854, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31902528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31902528</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31902528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.neuron.2019.12.007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Paloneva2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Paloneva, J., Mandelin, J., Kiialainen, A., Bohling, T., Prudlo, J., Hakola, P., Haltia, M., Konttinen, Y. T., Peltonen, L.
|
|
<strong>DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features.</strong>
|
|
J. Exp. Med. 198: 669-675, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12925681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12925681</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12925681[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=12925681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.20030027" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Paloneva2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L.
|
|
<strong>Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.</strong>
|
|
Am. J. Hum. Genet. 71: 656-662, 2002. Note: Erratum: Am. J. Hum. Genet. 72: 225 only, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12080485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12080485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12080485[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=12080485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/342259" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Schlepckow2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schlepckow, K., Kleinberger, G., Fukumori, A., Feederle, R., Lichtenthaler, S. F., Steiner, H., Haass, C.
|
|
<strong>An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function.</strong>
|
|
EMBO Molec. Med. 9: 1356-1365, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28855300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28855300</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28855300[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=28855300" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.15252/emmm.201707672" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Song2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Song, W., Hooli, B., Mullin, K., Jin, S. C., Cella, M., Ulland, T. K., Wang, Y., Tanzi, R. E., Colonna, M.
|
|
<strong>Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation.</strong>
|
|
Alzheimers Dement. 13: 381-387, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27520774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27520774</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27520774[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=27520774" 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.jalz.2016.07.004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Stefansson2024" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stefansson, H., Walters, G. B., Sveinbjornsson, G., Tragante, V., Einarsson, G., Helgason, H., Sigurdsson, A., Beyter, D., Snaebjarnarson, A. S., Ivarsdottir, E. V., Thorleifsson, G., Halldorsson, B. V., and 58 others.
|
|
<strong>Homozygosity for R47H in TREM2 and the risk of Alzheimer's disease.</strong>
|
|
New Eng. J. Med. 390: 2217-2219, 2024.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38899702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38899702</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38899702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMc2314334" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Sudom2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sudom, A., Talreja, S., Danao, J., Bragg, E., Kegel, R., Min, X., Richardson, J., Zhang, Z., Sharkov, N., Marcora, E., Thibault, S., Bradley, J., Wood, S., Lim, A.-C., Chen, H., Wang, S., Foltz, I. N., Sambashivan, S., Wang, Z.
|
|
<strong>Molecular basis for the loss-of-function effects of the Alzheimer's disease-associated R47H variant of the immune receptor TREM2.</strong>
|
|
J. Biol. Chem. 293: 12634-12646, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29794134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29794134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29794134[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=29794134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.RA118.002352" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Turnbull2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., Colonna, M.
|
|
<strong>Cutting edge: TREM-2 attenuates macrophage activation.</strong>
|
|
J. Immun. 177: 3520-3524, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16951310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16951310</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16951310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.4049/jimmunol.177.6.3520" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Yeh2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., Sheng, M.
|
|
<strong>TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid-beta by microglia.</strong>
|
|
Neuron 91: 328-340, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27477018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27477018</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27477018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.neuron.2016.06.015" 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">
|
|
Ada Hamosh - updated : 09/25/2024
|
|
</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">
|
|
Bao Lige - updated : 12/18/2020<br>Ada Hamosh - updated : 01/15/2020<br>Ada Hamosh - updated : 10/17/2018<br>Bao Lige - updated : 08/21/2018<br>Cassandra L. Kniffin - updated : 12/3/2015<br>Paul J. Converse - updated : 9/9/2015<br>Ada Hamosh - updated : 2/8/2013<br>Paul J. Converse - updated : 3/9/2007<br>Paul J. Converse - updated : 2/27/2006<br>Paul J. Converse - updated : 11/11/2005<br>Cassandra L. Kniffin - updated : 8/24/2005<br>Victor A. McKusick - updated : 9/17/2002
|
|
</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">
|
|
Paul J. Converse : 6/28/2000
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/25/2024
|
|
</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">
|
|
mgross : 12/18/2020<br>joanna : 09/17/2020<br>alopez : 01/15/2020<br>carol : 11/19/2018<br>carol : 11/16/2018<br>carol : 10/19/2018<br>alopez : 10/18/2018<br>alopez : 10/17/2018<br>mgross : 08/21/2018<br>alopez : 12/11/2015<br>ckniffin : 12/3/2015<br>mgross : 9/9/2015<br>carol : 9/16/2013<br>alopez : 2/14/2013<br>terry : 2/8/2013<br>mgross : 3/13/2007<br>mgross : 3/13/2007<br>terry : 3/9/2007<br>mgross : 3/9/2006<br>terry : 2/27/2006<br>mgross : 11/15/2005<br>terry : 11/11/2005<br>carol : 10/12/2005<br>wwang : 8/26/2005<br>ckniffin : 8/24/2005<br>carol : 7/10/2003<br>alopez : 9/19/2002<br>carol : 9/17/2002<br>alopez : 4/3/2002<br>mgross : 6/28/2000
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 605086
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 2; TREM2
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: TREM2</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 6p21.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 6:41,158,508-41,163,116 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
6p21.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Alzhieimer disease 17, susceptibility to}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
615080
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
618193
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal 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 TREM2 gene encodes a type I transmembrane protein that is a member of the immunoglobulin (Ig) receptor superfamily. It contains an ectodomain, a transmembrane domain, and a short cytoplasmic tail. TREM2 is found on the surface of osteoclasts, immature dendritic cells, and macrophages. In the central nervous system, TREM2 is primarily expressed in microglia (summary by Atagi et al., 2015). </p><p>Monocyte/macrophage- and neutrophil-mediated inflammatory responses can be stimulated through a variety of receptors, including G protein-linked 7-transmembrane receptors (e.g., FPR1; 136537), Fc receptors (see 146790), CD14 (158120) and Toll-like receptors (e.g., TLR4; 603030), and cytokine receptors (e.g., IFNGR1; 107470). Engagement of these receptors can also prime myeloid cells to respond to other stimuli. Myeloid cells express receptors belonging to the Ig superfamily, such as TREM2, or to the C-type lectin superfamily. Depending on their transmembrane and cytoplasmic sequence structure, these receptors have either activating (e.g., KIR2DS1; 604952) or inhibitory functions (e.g., KIR2DL1; 604936). TREM2 is an activating receptor that is expressed on macrophages and dendritic cells (Bouchon et al., 2000). </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>By searching an EST database with TREM1 (605085) as the probe, Bouchon et al. (2000) identified a cDNA encoding TREM2. The predicted 230-amino acid TREM2 protein was expressed on macrophages and dendritic cells but not on granulocytes or monocytes, suggesting a role for TREM2 in chronic rather than acute inflammatory conditions. </p><p>Using flow cytometric analysis, Turnbull et al. (2006) demonstrated that murine Trem2 was expressed on macrophages recruited to peripheral tissues, but not on tissue-resident macrophages, circulating cells, or myeloid progenitors. Il4 (147780) induced expression of Trem2 on resident peritoneal cells. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By genomic sequence analysis, Allcock et al. (2003) determined that all genes in the TREM cluster have an exon encoding the 5-prime UTR and leader peptide, a second exon encoding the IgV domain, and a variable number of downstream exons encoding the stalk, transmembrane, and cytoplasmic regions. TREM2 contains 5 exons. A soluble splice variant of TREM2 lacks exon 4, which encodes the transmembrane region. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By somatic cell hybrid analysis, Bouchon et al. (2000) mapped the TREM1 and TREM2 genes to chromosome 6, where LY95 (604531) is located. By genomic sequence analysis, Allcock et al. (2003) mapped the TREM2 gene to chromosome 6p21.1, within a TREM gene cluster. The mouse Trem2 gene maps to chromosome 17 in a region that shows homology of synteny to human chromosome 6. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>TREM2 forms a receptor signaling complex with TYROBP (604142) (Campbell and Colonna, 1999; Bouchon et al., 2001) and triggers activation of the immune responses in macrophages and dendritic cells (Lanier and Bakker, 2000). Patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), in whom mutations in the TYROBP (PLOSL1; 221770) or TREM2 (PLOSL2; 618193) genes have been identified, have no defects in cell-mediated immunity, suggesting a remarkable capacity of the human immune system to compensate for the inactive TYROBP-mediated activation pathway. The data of Paloneva et al. (2002) suggested that the TYROBP-mediated signaling pathway plays a significant role in human brain and bone tissue and provide an interesting example of how mutations in 2 different subunits of a multisubunit receptor complex result in an identical human disease phenotype. </p><p>Paloneva et al. (2003) analyzed differentiation of peripheral blood mononuclear cells from DAP12 (TYROBP)- and TREM2-deficient Finnish or German PLOSL patients into osteoclasts. They found that homozygous loss-of-function mutations in DAP12 or TREM2 resulted in inefficient, aberrant, and delayed differentiation into osteoclasts and significantly diminished bone resorption capability in vitro. RT-PCR analysis detected no differences between patient and control cells in the expression of several genes, but expression of DAP12 and TREM2 increased in control cells during osteoclastic differentiation. Paloneva et al. (2003) concluded that the DAP12-TREM2 signaling complex is important in the differentiation and function of osteoclasts. Independently, Cella et al. (2003) also showed that TREM2-deficient patients have impaired osteoclast differentiation and function. </p><p>Bailey et al. (2015) and Atagi et al. (2015) independently identified ApoE (107741) and APOA1 (107680) as binding ligands for TREM2. In vitro studies showed that binding of APOE to TREM2 was associated with increased phagocytosis of apoE-bound apoptotic neurons by primary microglia in a manner that was dependent on TREM2 expression. Expression of the TREM2 variant R47H (rs75932628) dramatically reduced the affinity of APOE for TREM2. The findings established a critical role for TREM2 in regulating the neuroinflammatory environment, and demonstrated a biochemical link between 2 proteins associated with the development of Alzheimer disease (see, e.g., AD17, 615080). Furthermore, Bailey et al. (2015) suggested that the R47H variant may reduce the ability of TREM2+ phagocytes to bind APOE within senile plaques, thereby decreasing the clearance of beta-amyloid (APP; 104760) from the brain. </p><p>Schlepckow et al. (2017) determined that TREM2 is shed by proteases of the ADAM family C-terminal to histidine-157, a position where an Alzheimer disease-associated coding variant (H157Y) was discovered in the Han Chinese population (Jiang et al., 2016). Unlike mutations in the Ig-like domain, the H157Y variant within the stalk region leads to enhanced shedding of TREM2. Elevated ectodomain shedding reduces cell surface full-length TREM2 and lowers TREM2-dependent phagocytosis. </p><p>Using an unbiased protein microarray screen, Yeh et al. (2016) identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ, 185430 and APOE) as ligands of TREM2. Binding of these ligands by TREM2 was abolished or reduced by Alzheimer disease-associated risk variants (see MOLECULAR GENETICS). Overexpression of wildtype TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells, while TREM2 carrying disease-associated variants was impaired in this activity. TREM2-knockout microglia showed reduced internalization of LDL and CLU. Beta-amyloid binds to lipoproteins, and this complex was taken up by microglia in a TREM2-dependent manner. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Sudom et al. (2018) reported 3 high-resolution structures for the extracellular ligand-binding domains of R47H mutant TREM2, apolipoprotein-bound wildtype, and phosphatidylserine-bound wildtype TREM2 at 1.8, 2.2, and 2.2 angstroms, respectively. The structures revealed that arg47 plays a critical role in maintaining the structural features of the complementarity-determining region-2 (CDR2) loop and the putative positive ligand-interacting surface (PLIS), stabilizing conformations capable of ligand interaction. Sudom et al. (2018) concluded that, together with in vitro and in vivo characterization, their structural findings elucidated the molecular mechanism underlying loss of ligand binding, putative oligomerization, and functional activity of R47H TREM2. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 2</em></strong></p><p>
|
|
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a globally distributed recessively inherited disorder leading to death during the fifth decade of life and is characterized by early-onset progressive dementia and bone cysts. Mutations in the TYROBP gene had been shown to cause the disorder (see PLOSL1; 221770), but Paloneva et al. (2002) found that some patients with PLOSL did not have mutations in the TYROBP gene. Paloneva et al. (2002) studied the segregation of marker haplotypes flanking genes that encode polypeptides interacting with TYROBP. The only chromosomal region showing complete segregation to PLOSL was the 6p22-p21 region which includes the TREM2 gene. Mutations in this gene were identified in each of 2 affected families with PLOSL2 (618193), a Swedish and a Norwegian family, and subsequently in 3 other families. </p><p>In 6 patients with PLOSL2, including 2 sibs, Klunemann et al. (2005) identified 4 different homozygous mutations in the TREM2 gene (see, e.g., 605086.0006 and 605086.0007). </p><p><strong><em>Susceptibility to Alzheimer Disease 17</em></strong></p><p>
|
|
In a genomewide association study of 3,550 Icelandic individuals with Alzheimer disease (AD17; 615080) and a large number of controls, Jonsson et al. (2013) found a significant association between the T allele of an R47H (605086.0008) variation in the TREM2 gene (rs75932628) and risk of disease (odds ratio (OR) 2.92, p = 3.42 x 10(-10)). The association was stronger when the controls were older than 85 years. There were 4 homozygous carriers of the variant, 2 of whom were diagnosed with AD. The association was replicated among 2,037 AD cases and 9,727 controls (OR 2.83, p = 0.002). </p><p>In an association study of 279 patients with late-onset AD and 346 controls, all from a Chinese southern Han population, Ma et al. (2014) failed to detect the rs75932628T variant. </p><p>By high-throughput sequencing of the TREM2 gene in 988 late-onset AD patients and 1,354 healthy controls, all of Han Chinese origin, Jiang et al. (2016) identified 4 rare coding variants and showed that one of these, H157Y (rs22342555), conferred risk of AD in their cohort. </p><p>Song et al. (2017) analyzed the AD risk of several TREM2 variants, compared each variant's risk and functional impact by reporter assay, and analyzed expression of TREM2 in human monocytes. Risk analysis was carried out in 1,376 participants (941 affected, 404 unaffected, 31 not determined) from 410 families from the National Institutes of Mental Health (NIMH) Alzheimer's Disease Genetics Initiative Study, and in 10,449 Caucasian cases and controls from the Alzheimer's Disease Sequencing Project (ADSP). The R47H variant had a profound negative effect on signaling in response to most tested lipid ligands, and H157Y demonstrated a lesser defect. Family-based association analysis in the NIMH AD families yielded a p value of .004 for R47H. The H157Y variant was found in 5 of 8 affected individuals and in no unaffected individuals. </p><p>In a study using pooled sequencing of 2,082 AD cases and 1,648 cognitively normal elderly controls of European American descent, Jin et al. (2014) identified 16 nonsynonymous variants in the TREM2 gene, of which 2 were significantly associated with disease risk in single variant analysis: R47H (odds ratio (OR) 2.63, p = 0.000917) and R62H (605086.0009) (OR 2.36, p = 0.000236). Additional variants were likely also to confer risk, as the association was still highly significant even after excluding R47H (OR 2.47, p = 0.000000537). </p><p>Li et al. (2021) performed a metaanalysis of 26 datasets comprising 28,007 AD cases and 45,121 controls. A significantly increased risk of AD was observed in R47H carriers versus noncarriers (OR 3.88, 95% CI, 3.17-4.76, p less than 0.001), R62H (OR 1.37, 95% CI, 1.11-1.70, p = 0.004), and H157Y (OR 4.22, 95% CI, 1.93-9.21, p less than 0.001). All of these variants are present primarily in individuals of European descent. </p><p>In a metaanalysis of 24,808 Alzheimer disease patients and 1,165,514 controls to examine the role of missense variants in TREM2, Stefansson et al. (2024) identified R47H as having an incomplete recessive effect (homozygotes for this variant are at a much greater risk of AD than heterozygotes). Individuals who were compound heterozygous for the R47H and R62H alleles had a higher risk of earlier onset of AD than heterozygotes for either, but much less risk than R47H homozygotes. Stefansson et al. (2024) noted that R47H homozygosity does not contribute to amyloid-beta overproduction but instead disrupts amyloid-beta clearance, leading to the accumulation of amyloid plaques. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Turnbull et al. (2006) found that mice lacking Trem2 were unable to inhibit cytokine production in response to microbial products. There was no difference in cytokine production by macrophages from Trem2-deficient mice and Dap12-deficient mice, leading Turnbull et al. (2006) to conclude that Trem2 is the receptor operative in the increased macrophage cytokine production observed in Dap12-deficient cells. They concluded that TREM2 expressed on newly differentiated and alternatively activated macrophages functions to restrain macrophage activation. </p><p>Guerreiro et al. (2013) showed that expression of Trem2 rose in parallel with a rise in cortical levels of beta-amyloid in the TgCRND8 mouse model of Alzheimer disease (AD; 104300). The dysregulation of expression induced by beta-amyloid (A-beta; see 104760) was relatively specific to Trem2, as its partner Tyrobp was not dysregulated. </p><p>Using immunohistochemistry, confocal microscopy, RT-PCR, and Western blot analyses, Jay et al. (2015) demonstrated increased expression of Trem2 in Iba1 (AIF1; 601833)-positive myeloid cells surrounding age-related A-beta plaque deposits in brains of 2 transgenic mouse models of AD. Similar expression patterns were observed in 2 neuropathologically confirmed human AD cases. Flow cytometric analysis showed that Trem2-positive macrophages surrounding A-beta deposits in transgenic mouse AD models expressed high levels of Cd45 (151460), a marker for peripherally derived macrophages. Transgenic AD mice lacking Trem2 had reduced A-beta plaque-associated macrophages, inflammation, hippocampal A-beta deposition, astrocytosis, and tau (MAPT; 157140) pathology. Jay et al. (2015) proposed that TREM2 has a role in AD pathology and in neuroinflammation in other central nervous system pathologies. </p><p>Filipello et al. (2018) found that Trem2 was selectively expressed by microglial cells in both cortex and hippocampus at different stages of neuronal development in mice. Trem2 -/- mice had fewer microglial cells than wildtype, and the cells became less activated in hippocampus during the early stages of brain development. Whole-cell recording of miniature excitatory postsynaptic currents (mEPSCs) in pyramidal neurons of acute brain slices showed that Trem2 deficiency caused enhanced pre- and postsynaptic contacts and increased electrophysiologic activity. Trem2 -/- microglial cells lacked synapse elimination that occurred through a process requiring cell-to-cell contact. Measurement of engulfment capacity with microglial cells from primary cell culture revealed that Trem2 -/- microglial cells displayed significantly reduced engulfment of synaptosomes compared with wildtype, confirming the role of Trem2 in synapse elimination during brain development. Absence of Trem2 in mice did not compromise the anatomic connections between brain regions, but rather it impaired function, as Trem2 -/- mice displayed an underconnectivity phenotype between prefrontal and hippocampal regions. Trem2 -/- mice exhibited a strong increase in self-grooming and were defective in social behavior. </p><p>Using Trem2 -/- mice subjected to a demyelinating cuprizone (CPZ) diet, Nugent et al. (2020) found that Trem2 deficiency prevented conversion from a homeostatic to a disease-associated microglia (DAM) state. Microglia from CPZ-challenged Trem2 -/- mice failed to upregulate lipid metabolism genes. Gene expression changes in microglia from CPZ-challenged Trem2 -/- mice were also present in aged Trem2 -/- microglia and were homogeneous across microglia, leading to neuronal damage during chronic demyelination. Chronic demyelination caused a profound alteration of cholesterol metabolism selectively in Trem2 -/- central nervous system, resulting in accumulated cholesteryl ester (CE) derived from myelin cholesterol in Trem2 -/- brain. This CE accumulation was because Trem2 -/- microglia were able to phagocytose myelin debris during demyelination but were unable to properly metabolize or mediate efflux of myelin lipids. Similar to Trem2 deficiency, Apoe deficiency caused microglial CE accumulation with CPZ. However, Apoe deficiency more broadly affected cholesterol metabolism in brain, as accumulation of CE also occurred in forebrain, glial cells, and cerebral spinal fluid. In vitro analysis showed that Trem2 bound myelin lipids and promoted downstream signaling, and as a result, myelin phagocytosis was impaired in Trem2 -/- cells. Analysis with myelin-treated Trem2-deficient mouse macrophages and human iPSC-derived microglia further revealed that CE accumulation was rescued by ACAT1 (607809) inhibitor and LXR agonist. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>9 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TREM2, TRP78TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893998,
|
|
|
|
|
|
gnomAD: rs104893998,
|
|
|
|
|
|
ClinVar: RCV000005523, RCV000721925
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Swedish families, Paloneva et al. (2002) found that members with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; 618193) had a homozygous G-to-A transition at position 233 of the TREM2 gene, changing tryptophan-78 to a translation termination codon (W78X). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TREM2, LYS186ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937876,
|
|
|
|
|
|
|
|
ClinVar: RCV000005524
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Norwegian family, Paloneva et al. (2002) found that members with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; 618193) had a homozygous 558G-T change in the TREM2 gene, resulting in a lys186-to-asn (K186N) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TREM2, ASP134GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28939079,
|
|
|
|
|
|
gnomAD: rs28939079,
|
|
|
|
|
|
ClinVar: RCV000005525
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an American family that originated from Slovakia that was reported to have polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; 618193) by Bird et al. (1983), Paloneva et al. (2002) identified homozygosity for a 401A-G substitution in the TREM2 gene, resulting in an asp134-to-gly (D134G) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TREM2, IVS3DS, T-C, +2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs386834144,
|
|
|
|
|
|
gnomAD: rs386834144,
|
|
|
|
|
|
ClinVar: RCV000050138, RCV001810417
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Italian sibs with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; 618193), Paloneva et al. (2002) identified a homozygous mutation in the splice donor consensus site at the second position of exon 3 (482+2T-C) in the TREM2 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TREM2, TRP44TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894001,
|
|
|
|
|
|
gnomAD: rs104894001,
|
|
|
|
|
|
ClinVar: RCV000005527
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Bolivian patient with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; 618193), Paloneva et al. (2002) identified a homozygous 132G-A mutation in the TREM2 gene, resulting in a trp44-to-ter (W44X) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TREM2, VAL126GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908402,
|
|
|
|
|
|
gnomAD: rs121908402,
|
|
|
|
|
|
ClinVar: RCV000005528, RCV000721926, RCV003398447
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; 618193), Klunemann et al. (2005) identified a homozygous 377T-G transversion in exon 2 of the TREM2 gene, resulting in a val126-to-gly (V126G) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TREM2, GLN33TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894002,
|
|
|
|
|
|
gnomAD: rs104894002,
|
|
|
|
|
|
ClinVar: RCV000005529, RCV000721927, RCV002512810, RCV004018565, RCV005089179
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Belgian sibs with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL2; 618193), Klunemann et al. (2005) identified a homozygous 97C-T transition in exon 2 of the TREM2 gene, resulting in a gln33-to-ter (Q33X) substitution and premature termination of the protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 ALZHEIMER DISEASE 17, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TREM2, ARG47HIS ({dbSNP rs75932628})
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV004731677
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By whole-genome analysis of 2,261 Icelandic individuals followed by imputation in 3,550 Alzheimer disease patients and over 100,000 controls, Jonsson et al. (2013) identified a SNP in the TREM2 gene, rs75932628, as significantly associated with Alzheimer disease. The T allele of rs75932628, which encodes an arg47-to-his (R47H) substitution, was found to confer a significant risk of Alzheimer disease in Iceland (OR 2.92, 95% CI, 2.09-4.09, p = 3.42 x 10(-10)). The allele frequency of rs75932628-T in cognitively intact controls 85 years of age or older (0.46%) was significant less than in controls under age 85 years (0.64%). </p><p>Stefansson et al. (2024) reported that the allele frequency of the R47H variant ranges from nearly absent (in non-Europeans) to 0.7% among Icelanders and 1.4% among Ashkenazi Jews. In a metaanalysis of 24,808 Alzheimer disease patients and 1,165,514 controls examining the role of missense variants in the TREM2, Stefansson et al. (2024) identified R47H as having an incomplete recessive effect (homozygotes for this variant are at a much greater risk of AD than heterozygotes). Homozygotes for R47H had a high risk (OR 97.1, 95% CI, 23.5-401.1) of developing Alzheimer disease, and at an earlier age than homozygotes for the APOE4 allele (see AD2, 104310). Individuals who were compound heterozygous for the R47H and R62H (605085.0009) alleles had a higher risk of earlier onset of AD than heterozygotes for either, but much less risk than R47H homozygotes. Mean age of onset was 6.4 years earlier among R47H homozygotes than other genotypes in the study. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 ALZHEIMER DISEASE 17, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TREM2, ARG62HIS ({dbSNP rs143332484})
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV004731676
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a study using pooled sequencing of 2,082 AD cases and 1,648 cognitively normal elderly controls of European American descent, Jin et al. (2014) identified the R62H variant in TREM2 as significantly associated with disease risk in single variant analysis (OR 2.36, p = 0.000236). </p><p>Stefansson et al. (2024) reported that the R62H allele confers a minor increased risk of AD in individuals from Iceland, compared with the R47H (605085.0008) allele. Compound heterozygotes for these 2 variants had an earlier age of onset of AD than heterozygotes for either, but still were at much lower risk than R47H homozygotes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Allcock, R. J. N., Barrow, A. D., Forbes, S., Beck, S., Trowsdale, J.
|
|
<strong>The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44.</strong>
|
|
Europ. J. Immun. 33: 567-577, 2003.
|
|
|
|
|
|
[PubMed: 12645956]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/immu.200310033]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeek, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., Younkin, S., Das, P., Fryer, J. D., Bu, G.
|
|
<strong>Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2).</strong>
|
|
J. Biol. Chem. 290: 26043-26050, 2015.
|
|
|
|
|
|
[PubMed: 26374899]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M115.679043]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bailey, C. C., DeVaux, L. B., Farzan, M.
|
|
<strong>The triggering receptor expressed on myeloid cells 2 binds apolipoprotein E.</strong>
|
|
J. Biol. Chem. 290: 26033-26042, 2015.
|
|
|
|
|
|
[PubMed: 26374897]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M115.677286]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bird, T. D., Koerker, R. M., Leaird, B. J., Vlcek, B. W., Thorning, D. R.
|
|
<strong>Lipomembranous polycystic osteodysplasia (brain, bone, and fat disease): a genetic cause of presenile dementia.</strong>
|
|
Neurology 33: 81-86, 1983.
|
|
|
|
|
|
[PubMed: 6681564]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.33.1.81]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bouchon, A., Dietrich, J., Colonna, M.
|
|
<strong>Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes.</strong>
|
|
J. Immun. 164: 4991-4995, 2000.
|
|
|
|
|
|
[PubMed: 10799849]
|
|
|
|
|
|
[Full Text: https://doi.org/10.4049/jimmunol.164.10.4991]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bouchon, A., Hernandez-Munain, C., Cella, M., Colonna, M.
|
|
<strong>A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells.</strong>
|
|
J. Exp. Med. 194: 1111-1122, 2001.
|
|
|
|
|
|
[PubMed: 11602640]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.194.8.1111]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Campbell, K. S., Colonna, M.
|
|
<strong>DAP12: a key accessory protein for relaying signals by natural killer cell receptors.</strong>
|
|
Int. J. Biochem. Cell Biol. 31: 631-636, 1999.
|
|
|
|
|
|
[PubMed: 10404635]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1357-2725(99)00022-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cella, M., Buonsanti, C., Strader, C., Kondo, T., Salmaggi, A., Colonna, M.
|
|
<strong>Impaired differentiation of osteoclasts in TREM-2-deficient individuals.</strong>
|
|
J. Exp. Med. 198: 645-651, 2003.
|
|
|
|
|
|
[PubMed: 12913093]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20022220]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Filipello, F., Morini, R., Corradini, I., Zerbi, V., Canzi, A., Michalski, B., Erreni, M., Markicevic, M., Starvaggi-Cucuzza, C., Otero, K., Piccio, L., Cignarella, F., and 9 others.
|
|
<strong>The microglial innate immune receptor TREM2 is required for synapse elimination and normal brain connectivity.</strong>
|
|
Immunity 48: 979-991, 2018.
|
|
|
|
|
|
[PubMed: 29752066]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.immuni.2018.04.016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majournie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., Hazrati, L., Collinge, J., and 12 others.
|
|
<strong>TREM2 variants in Alzheimer's disease.</strong>
|
|
New Eng. J. Med. 368: 117-127, 2013.
|
|
|
|
|
|
[PubMed: 23150934]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa1211851]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., Cotleur, A. C., Butovsky, O., Bekris, L., Staugaitis, S. M., Leverenz, J. B., Pimplikar, S. W., Landreth, G. E., Howell, G. R., Ransohoff, R. M., Lamb, B. T.
|
|
<strong>TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer's disease mouse models.</strong>
|
|
J. Exp. Med. 212: 287-295, 2015.
|
|
|
|
|
|
[PubMed: 25732305]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20142322]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jiang, T., Tan, L., Chen, Q., Tan, M.-S., Zhou, J.-S., Zhu, X.-C., Lu, H., Wang, H.-F., Zhang, Y.-D., Yu, J.-T.
|
|
<strong>A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese.</strong>
|
|
Neurobiol. Aging 42: 217.e1-217.e3, 2016. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 27067662]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neurobiolaging.2016.02.023]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jin, S. C., Benitez, B. A., Karch, C. M., Cooper, B., Skorupa, T., Carrell, D., Norton, J. B., Hsu, S., Harari, O., Cai, Y., Bertelsen, S., Goate, A. M., Cruchaga, C.
|
|
<strong>Coding variants in TREM2 increase risk for Alzheimer's disease.</strong>
|
|
Hum. Molec. Genet. 23: 5838-5846, 2014.
|
|
|
|
|
|
[PubMed: 24899047]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddu277]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., Rujescu, D., Hampel, H., and 12 others.
|
|
<strong>Variant of TREM2 associated with the risk of Alzheimer's disease.</strong>
|
|
New Eng. J. Med. 368: 107-116, 2013.
|
|
|
|
|
|
[PubMed: 23150908]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa1211103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Klunemann, H. H., Ridha, B. H., Magy, L., Wherrett, J. R., Hemelsoet, D. M., Keen, R. W., De Bleecker, J. L., Rossor, M. N., Marienhagen, J., Klein, H. E., Peltonen, L., Paloneva, J.
|
|
<strong>The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2.</strong>
|
|
Neurology 64: 1502-1507, 2005.
|
|
|
|
|
|
[PubMed: 15883308]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.WNL.0000160304.00003.CA]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lanier, L. L., Bakker, A. B. H.
|
|
<strong>The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function.</strong>
|
|
Immun. Today 21: 611-614, 2000.
|
|
|
|
|
|
[PubMed: 11114420]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0167-5699(00)01745-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, R., Wang, X., He, P.
|
|
<strong>The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta-analysis.</strong>
|
|
Exp. Ther. Med. 21: 347, 2021.
|
|
|
|
|
|
[PubMed: 33732320]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3892/etm.2021.9778]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ma, J., Zhou, Y., Xu, J., Liu, X., Wang, Y., Deng, Y., Wang, G., Xu, W., Ren, R., Liu, X., Zhang, Y., Wang, C., Tang, H., Chen, S.
|
|
<strong>Association study of TREM2 polymorphism rs75932628 with late-onset Alzheimer's disease in Chinese Han population.</strong>
|
|
Neurol. Res. 36: 894-896, 2014.
|
|
|
|
|
|
[PubMed: 24725293]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1179/1743132814Y.0000000376]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nugent, A. A., Lin, K., van Lengerich, B., Lianoglou, S., Przbyla, L., Davis, S. S., Llapashtica, C., Wang, J., Kim, D. J., Xia, D., Lucas, A., Baskaran, S., and 18 others.
|
|
<strong>TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge.</strong>
|
|
Neuron 105: 837-854, 2020.
|
|
|
|
|
|
[PubMed: 31902528]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neuron.2019.12.007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Paloneva, J., Mandelin, J., Kiialainen, A., Bohling, T., Prudlo, J., Hakola, P., Haltia, M., Konttinen, Y. T., Peltonen, L.
|
|
<strong>DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features.</strong>
|
|
J. Exp. Med. 198: 669-675, 2003.
|
|
|
|
|
|
[PubMed: 12925681]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20030027]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., Peltonen, L.
|
|
<strong>Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype.</strong>
|
|
Am. J. Hum. Genet. 71: 656-662, 2002. Note: Erratum: Am. J. Hum. Genet. 72: 225 only, 2003.
|
|
|
|
|
|
[PubMed: 12080485]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/342259]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schlepckow, K., Kleinberger, G., Fukumori, A., Feederle, R., Lichtenthaler, S. F., Steiner, H., Haass, C.
|
|
<strong>An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function.</strong>
|
|
EMBO Molec. Med. 9: 1356-1365, 2017.
|
|
|
|
|
|
[PubMed: 28855300]
|
|
|
|
|
|
[Full Text: https://doi.org/10.15252/emmm.201707672]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Song, W., Hooli, B., Mullin, K., Jin, S. C., Cella, M., Ulland, T. K., Wang, Y., Tanzi, R. E., Colonna, M.
|
|
<strong>Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation.</strong>
|
|
Alzheimers Dement. 13: 381-387, 2017.
|
|
|
|
|
|
[PubMed: 27520774]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.jalz.2016.07.004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stefansson, H., Walters, G. B., Sveinbjornsson, G., Tragante, V., Einarsson, G., Helgason, H., Sigurdsson, A., Beyter, D., Snaebjarnarson, A. S., Ivarsdottir, E. V., Thorleifsson, G., Halldorsson, B. V., and 58 others.
|
|
<strong>Homozygosity for R47H in TREM2 and the risk of Alzheimer's disease.</strong>
|
|
New Eng. J. Med. 390: 2217-2219, 2024.
|
|
|
|
|
|
[PubMed: 38899702]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMc2314334]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sudom, A., Talreja, S., Danao, J., Bragg, E., Kegel, R., Min, X., Richardson, J., Zhang, Z., Sharkov, N., Marcora, E., Thibault, S., Bradley, J., Wood, S., Lim, A.-C., Chen, H., Wang, S., Foltz, I. N., Sambashivan, S., Wang, Z.
|
|
<strong>Molecular basis for the loss-of-function effects of the Alzheimer's disease-associated R47H variant of the immune receptor TREM2.</strong>
|
|
J. Biol. Chem. 293: 12634-12646, 2018.
|
|
|
|
|
|
[PubMed: 29794134]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.RA118.002352]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., Colonna, M.
|
|
<strong>Cutting edge: TREM-2 attenuates macrophage activation.</strong>
|
|
J. Immun. 177: 3520-3524, 2006.
|
|
|
|
|
|
[PubMed: 16951310]
|
|
|
|
|
|
[Full Text: https://doi.org/10.4049/jimmunol.177.6.3520]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., Sheng, M.
|
|
<strong>TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid-beta by microglia.</strong>
|
|
Neuron 91: 328-340, 2016.
|
|
|
|
|
|
[PubMed: 27477018]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neuron.2016.06.015]
|
|
|
|
|
|
</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">
|
|
Ada Hamosh - updated : 09/25/2024<br>Bao Lige - updated : 12/18/2020<br>Ada Hamosh - updated : 01/15/2020<br>Ada Hamosh - updated : 10/17/2018<br>Bao Lige - updated : 08/21/2018<br>Cassandra L. Kniffin - updated : 12/3/2015<br>Paul J. Converse - updated : 9/9/2015<br>Ada Hamosh - updated : 2/8/2013<br>Paul J. Converse - updated : 3/9/2007<br>Paul J. Converse - updated : 2/27/2006<br>Paul J. Converse - updated : 11/11/2005<br>Cassandra L. Kniffin - updated : 8/24/2005<br>Victor A. McKusick - updated : 9/17/2002
|
|
</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">
|
|
Paul J. Converse : 6/28/2000
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/25/2024<br>mgross : 12/18/2020<br>joanna : 09/17/2020<br>alopez : 01/15/2020<br>carol : 11/19/2018<br>carol : 11/16/2018<br>carol : 10/19/2018<br>alopez : 10/18/2018<br>alopez : 10/17/2018<br>mgross : 08/21/2018<br>alopez : 12/11/2015<br>ckniffin : 12/3/2015<br>mgross : 9/9/2015<br>carol : 9/16/2013<br>alopez : 2/14/2013<br>terry : 2/8/2013<br>mgross : 3/13/2007<br>mgross : 3/13/2007<br>terry : 3/9/2007<br>mgross : 3/9/2006<br>terry : 2/27/2006<br>mgross : 11/15/2005<br>terry : 11/11/2005<br>carol : 10/12/2005<br>wwang : 8/26/2005<br>ckniffin : 8/24/2005<br>carol : 7/10/2003<br>alopez : 9/19/2002<br>carol : 9/17/2002<br>alopez : 4/3/2002<br>mgross : 6/28/2000
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|