6394 lines
597 KiB
Text
6394 lines
597 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
|
|
|
|
- *120700 - COMPLEMENT COMPONENT 3; C3
|
|
|
|
|
|
- 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=120700"><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">*120700</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="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#evolution">Evolution</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/120700">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></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=ENSG00000125730;t=ENST00000245907" 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=718" 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=120700" 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=ENSG00000125730;t=ENST00000245907" 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_000064" 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_000064" 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=120700" 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=00400&isoform_id=00400_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/C3" 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/179665,181130,40786791,58194075,115298678,119370332,119589476,119589477,152012494,152012784,194384410,211947869,2173422661" 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/P01024" 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=718" 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=ENSG00000125730;t=ENST00000245907" 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=C3" 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=C3" 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+718" 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/C3" 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:718" 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/718" 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=chr19&hgg_gene=ENST00000245907.11&hgg_start=6677704&hgg_end=6720650&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:1318" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=120700[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=120700[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/C3/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000125730" 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=C3" 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=C3" 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=C3" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://structure.bmc.lu.se/idbase/C3base/index.php" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=C3&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/PA25897" 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:1318" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0267488.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:88227" 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/C3#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:88227" 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/718/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://omia.org/OMIA000155/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=718" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-030131-2211" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:718" 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=C3&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 771443008<br />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
120700
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
COMPLEMENT COMPONENT 3; C3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
C3a, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
C3b, INCLUDED<br />
|
|
C3c, INCLUDED<br />
|
|
C3d, INCLUDED<br />
|
|
ACYLATION-STIMULATING PROTEIN, INCLUDED; ASP, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=C3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">C3</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/19/189?start=-3&limit=10&highlight=189">19p13.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:6677704-6720650&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'})">19:6,677,704-6,720,650</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=612925,611378,613779" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/19/189?start=-3&limit=10&highlight=189">
|
|
19p13.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Hemolytic uremic syndrome, atypical, susceptibility to, 5}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/612925"> 612925 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Macular degeneration, age-related, 9}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/611378"> 611378 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
C3 deficiency
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613779"> 613779 </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/120700" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/120700" 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 complement system is an important mediator of natural and acquired immunity. It consists of approximately 30 proteins that can exhibit catalytic activity, function as regulators, or act as cellular surface receptors. These components normally circulate in inactive forms and are activated by the classical, alternative, or lectin pathways. Complement component 3 plays a central role in all 3 activation pathways (summary by <a href="#54" class="mim-tip-reference" title="Reis, E. S., Falcao, D. A., Isaac, L. <strong>Clinical aspects and molecular basis of primary deficiencies of complement component C3 and its regulatory proteins factor I and factor H.</strong> Scand. J. Immun. 63: 155-168, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16499568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16499568</a>] [<a href="https://doi.org/10.1111/j.1365-3083.2006.01729.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16499568">Reis et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16499568" 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>For a review of the complement system and its components, see <a href="#23" class="mim-tip-reference" title="Degn, S. E., Jensenius, J. C., Thiel, S. <strong>Disease-causing mutations in genes of the complement system.</strong> Am. J. Hum. Genet. 88: 689-705, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21664996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21664996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21664996[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.ajhg.2011.05.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21664996">Degn et al. (2011)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21664996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#22" class="mim-tip-reference" title="de Bruijn, M. H. L., Fey, G. H. <strong>Human complement component C3: cDNA coding sequence and derived primary structure.</strong> Proc. Nat. Acad. Sci. 82: 708-712, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2579379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2579379</a>] [<a href="https://doi.org/10.1073/pnas.82.3.708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2579379">De Bruijn and Fey (1985)</a> presented the complete coding sequence of the C3 gene and the derived amino acid sequence. C3 is an acute phase reactant; increased synthesis of C3 is induced during acute inflammation. The liver is the main site of synthesis, although small amounts are also produced by activated monocytes and macrophages. A single chain precursor (pro-C3) of approximately 200 kD is found intracellularly; the cDNA shows that it comprises 1,663 amino acids. This is processed by proteolytic cleavage into alpha (C3a) and beta (C3b) subunits which in the mature protein are linked by disulfide bonds. Pro-C3 contains a signal peptide of 22 amino acid residues, the beta chain (645 residues) and the alpha chain (992 residues). The 2 chains are joined by 4 arginine residues that are not present in the mature protein. Human C3 has 79% identity to mouse C3 at the nucleotide level and 77% at the amino acid level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2579379" 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="#40" class="mim-tip-reference" title="Janssen, B. J. C., Huizinga, E. G., Raaijmakers, H. C. A., Roos, A., Daha, M. R., Nilsson-Ekdahl, K., Nilsson, B., Gros, P. <strong>Structures of complement component C3 provide insights into the function and evolution of immunity.</strong> Nature 437: 505-511, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16177781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16177781</a>] [<a href="https://doi.org/10.1038/nature04005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16177781">Janssen et al. (2005)</a> presented the crystal structures of native C3 and its final major proteolytic fragment C3c. The structures revealed 13 domains, 9 of which were unpredicted, and suggested that the proteins of the alpha-2-macroglobulin family evolved from a core of 8 homologous domains. A double mechanism prevents hydrolysis of the thioester group, essential for covalent attachment of activated C3 to target surfaces. Marked conformational changes in the alpha chain, including movement of a critical interaction site through a ring formed by the domains of the beta chain, indicated an unprecedented, conformation-dependent mechanism of activation, regulation, and biologic function of C3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16177781" 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="#39" class="mim-tip-reference" title="Janssen, B. J. C., Christodoulidou, A., McCarthy, A., Lambris, J. D., Gros, P. <strong>Structure of C3b reveals conformational changes that underlie complement activity.</strong> Nature 444: 213-216, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17051160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17051160</a>] [<a href="https://doi.org/10.1038/nature05172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17051160">Janssen et al. (2006)</a> presented the crystal structure at 4-angstrom resolution of the activated complement protein C3b and described the conformation rearrangements of the 12 domains that take place upon proteolytic activation. In the activated form the thioester is fully exposed for covalent attachment to target surfaces and is more than 85 angstroms away from the buried site in native C3. Marked domain rearrangements in the alpha chain present an altered molecular surface, exposing hidden and cryptic sites that are consistent with known putative binding sites of factor B (CFB; <a href="/entry/138470">138470</a>) and several complement regulators. The structural data indicated that the large conformational changes in the proteolytic activation and regulation of C3 take place mainly in the first conversion step, from C3 to C3b. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17051160" 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="#71" class="mim-tip-reference" title="Wiesmann, C., Katschke, K. J., Jr., Yin, J., Helmy, K. Y., Steffek, M., Fairbrother, W. J., McCallum, S. A., Embuscado, L., DeForge, L., Hass, P. E., van Lookeren Campagne, M. <strong>Structure of C3b in complex with CRIg gives insights into regulation of complement activation.</strong> Nature 444: 217-220, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17051150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17051150</a>] [<a href="https://doi.org/10.1038/nature05263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17051150">Wiesmann et al. (2006)</a> presented the crystal structure of C3b in complex with CRIG (<a href="/entry/300353">300353</a>) and, using CRIG mutants, provided evidence that CRIG acts as an inhibitor of the alternative pathway of complement. The structure shows that activation of C3 induces major structural rearrangements, including a dramatic movement (greater than 80 angstroms) of the thioester bond-containing domain through which C3b attaches to pathogen surfaces. <a href="#71" class="mim-tip-reference" title="Wiesmann, C., Katschke, K. J., Jr., Yin, J., Helmy, K. Y., Steffek, M., Fairbrother, W. J., McCallum, S. A., Embuscado, L., DeForge, L., Hass, P. E., van Lookeren Campagne, M. <strong>Structure of C3b in complex with CRIg gives insights into regulation of complement activation.</strong> Nature 444: 217-220, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17051150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17051150</a>] [<a href="https://doi.org/10.1038/nature05263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17051150">Wiesmann et al. (2006)</a> showed that CRIG is not only a phagocytic receptor, but also a potent inhibitor of the alternative pathway convertases. <a href="#71" class="mim-tip-reference" title="Wiesmann, C., Katschke, K. J., Jr., Yin, J., Helmy, K. Y., Steffek, M., Fairbrother, W. J., McCallum, S. A., Embuscado, L., DeForge, L., Hass, P. E., van Lookeren Campagne, M. <strong>Structure of C3b in complex with CRIg gives insights into regulation of complement activation.</strong> Nature 444: 217-220, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17051150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17051150</a>] [<a href="https://doi.org/10.1038/nature05263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17051150">Wiesmann et al. (2006)</a> concluded that the structure provides insights into the complex macromolecular structural rearrangements that occur during complement activation and inhibition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17051150" 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="#30" class="mim-tip-reference" title="Forneris, F., Ricklin, D., Wu, J., Tzekou, A., Wallace, R. S., Lambris, J. D., Gros, P. <strong>Structures of C3b in complex with factors B and D give insight into complement convertase formation.</strong> Science 330: 1816-1820, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21205667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21205667</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21205667[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1195821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21205667">Forneris et al. (2010)</a> presented crystal structures of the proconvertase C3bB at 4-angstrom resolution and its complex with factor D at 3.5-angstrom resolution. Their data showed how factor B binding to C3b forms an open 'activation' state of C3bB. Factor D specifically binds the open conformation of factor B through a site distant from the catalytic center and is activated by the substrate, which displaces factor D's self-inhibitory loop. This concerted proteolytic mechanism, which if cofactor-dependent and substrate-induced, restricts complement amplification to C3b-tagged target cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21205667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The report of <a href="#1" class="mim-tip-reference" title="Ajees, A. A., Gunasekaran, K., Volanakis, J. E., Narayana, S. V. L., Kotwal, G. J., Krishna Murthy, H. M. <strong>The structure of complement C3b provides insights into complement activation and regulation.</strong> Nature 444: 221-225, 2006. Note: Retraction: Nature 532: 268 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17051152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17051152</a>] [<a href="https://doi.org/10.1038/nature05258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17051152">Ajees et al. (2006)</a> that presented a structure of C3b was retracted by the journal Nature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17051152" 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>Component C3 plays several important biologic roles in the classical, alternative, and lectin activation pathways, e.g., (1) formation of C3- and C5-convertases, both essential for the full activation of the system; (2) production of opsonins that enhance phagocytosis of microorganisms; (3) degranulation of mast cells and basophils medicated by the fragments C3a and C5a; (4) solubilization and clearance of C3b-bound immune complexes; (5) adjuvant function of fragments C3d and C3dg; and (6) clearance of apoptotic cells (summary by <a href="#54" class="mim-tip-reference" title="Reis, E. S., Falcao, D. A., Isaac, L. <strong>Clinical aspects and molecular basis of primary deficiencies of complement component C3 and its regulatory proteins factor I and factor H.</strong> Scand. J. Immun. 63: 155-168, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16499568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16499568</a>] [<a href="https://doi.org/10.1111/j.1365-3083.2006.01729.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16499568">Reis et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16499568" 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>Polymorphisms in complement factor H (CFH; <a href="/entry/134370">134370</a>), the main regulator of the activation of C3, have been associated with susceptibility to age-related macular degeneration (see ARMD4, <a href="/entry/610698">610698</a>). <a href="#59" class="mim-tip-reference" title="Sivaprasad, S., Adewoyin, T., Bailey, T. A., Dandekar, S. S., Jenkins, S., Webster, A. R., Chong, N. V. <strong>Estimation of systemic complement C3 activity in age-related macular degeneration.</strong> Arch. Ophthal. 125: 515-519, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17420372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17420372</a>] [<a href="https://doi.org/10.1001/archopht.125.4.515" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17420372">Sivaprasad et al. (2007)</a> noted that only the C3a des Arg form of C3a is present in human plasma. They therefore studied the levels of C3a des Arg in 84 persons with a clinical diagnosis of ARMD compared with those in age-matched controls. The levels were significantly raised in the patient group compared with those in the control group. <a href="#59" class="mim-tip-reference" title="Sivaprasad, S., Adewoyin, T., Bailey, T. A., Dandekar, S. S., Jenkins, S., Webster, A. R., Chong, N. V. <strong>Estimation of systemic complement C3 activity in age-related macular degeneration.</strong> Arch. Ophthal. 125: 515-519, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17420372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17420372</a>] [<a href="https://doi.org/10.1001/archopht.125.4.515" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17420372">Sivaprasad et al. (2007)</a> also found that the concentration of plasma C3a des Arg did not differ significantly between those with different CFH genotypes. The authors suggested that systemic activation of the complement system may contribute to the pathogenesis of ARMD independent of CFH polymorphism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17420372" 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 immunofluorescence microscopy, <a href="#51" class="mim-tip-reference" title="Rahpeymai, Y., Hietala, M. A., Wilhelmsson, U., Fotheringham, A., Davies, I., Nilsson, A.-K., Zwirner, J., Wetsel, R. A., Gerard, C., Pekny, M., Pekna, M. <strong>Complement: a novel factor in basal and ischemia-induced neurogenesis.</strong> EMBO J. 25: 1364-1374, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16498410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16498410</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16498410[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/sj.emboj.7601004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16498410">Rahpeymai et al. (2006)</a> demonstrated that mouse neural progenitor cells and immature neurons expressed C3ar (<a href="/entry/605246">605246</a>) and C5ar (<a href="/entry/113995">113995</a>). Mice lacking C3 or C3ar, or treated with a C3ar antagonist, show decreased basal neurogenesis and impaired ischemia-induced neurogenesis in the subventricular zone and in the ischemic region. <a href="#51" class="mim-tip-reference" title="Rahpeymai, Y., Hietala, M. A., Wilhelmsson, U., Fotheringham, A., Davies, I., Nilsson, A.-K., Zwirner, J., Wetsel, R. A., Gerard, C., Pekny, M., Pekna, M. <strong>Complement: a novel factor in basal and ischemia-induced neurogenesis.</strong> EMBO J. 25: 1364-1374, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16498410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16498410</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16498410[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/sj.emboj.7601004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16498410">Rahpeymai et al. (2006)</a> concluded that, in the adult mammalian CNS, complement activation products promote both basal and ischemia-induced neurogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16498410" 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 proteomic analysis on human psoriatic epidermis (see <a href="/entry/177900">177900</a>), <a href="#57" class="mim-tip-reference" title="Schonthaler, H. B., Guinea-Viniegra, J., Wculek, S. K., Ruppen, I., Ximenez-Embun, P., Guio-Carrion, A., Navarro, R., Hogg, N., Ashman, K., Wagner, E. F. <strong>S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3.</strong> Immunity 39: 1171-1181, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24332034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24332034</a>] [<a href="https://doi.org/10.1016/j.immuni.2013.11.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24332034">Schonthaler et al. (2013)</a> identified S100A8 (<a href="/entry/123885">123885</a>) and S100A9 (<a href="/entry/123886">123886</a>), followed by C3, as the most upregulated proteins specifically expressed in lesional psoriatic skin. Confocal microscopy of human primary keratinocytes treated with TPA (PLAT; <a href="/entry/173370">173370</a>) demonstrated a strong increase in nuclear as opposed to cytoplasmic expression of S100A9. <a href="#57" class="mim-tip-reference" title="Schonthaler, H. B., Guinea-Viniegra, J., Wculek, S. K., Ruppen, I., Ximenez-Embun, P., Guio-Carrion, A., Navarro, R., Hogg, N., Ashman, K., Wagner, E. F. <strong>S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3.</strong> Immunity 39: 1171-1181, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24332034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24332034</a>] [<a href="https://doi.org/10.1016/j.immuni.2013.11.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24332034">Schonthaler et al. (2013)</a> deleted S100a9 in the Jun (<a href="/entry/165160">165160</a>)/JunB (<a href="/entry/165161">165161</a>) double-knockout (DKO) mouse model of psoriasis and observed an absence of scaly plaques on the ears and tails, as well as decreased amounts of C3. Inhibition of C3 in DKO mice also strongly reduced inflammatory skin disease. Chromatin immunoprecipitation analysis using DKO cells and S100a9 DKO -/- cells as controls demonstrated binding of S100a9 to the C3 promoter region. Chromatin immunoprecipitation analysis on human keratinocytes also suggested binding of S100A9 to the C3 promoter. <a href="#57" class="mim-tip-reference" title="Schonthaler, H. B., Guinea-Viniegra, J., Wculek, S. K., Ruppen, I., Ximenez-Embun, P., Guio-Carrion, A., Navarro, R., Hogg, N., Ashman, K., Wagner, E. F. <strong>S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3.</strong> Immunity 39: 1171-1181, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24332034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24332034</a>] [<a href="https://doi.org/10.1016/j.immuni.2013.11.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24332034">Schonthaler et al. (2013)</a> concluded that S100A8/S100A9 regulates C3 at the nuclear level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24332034" 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="#47" class="mim-tip-reference" title="Nan, R., Tetchner, S., Rodriguez, E., Pao, P.-J., Gor, J., Lengyel, I., Perkins, S. J. <strong>Zinc-induced self-association of complement C3b and factor H: implications for inflammation and age-related macular degeneration.</strong> J. Biol. Chem. 288: 19197-19210, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23661701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23661701</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23661701[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.M113.476143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23661701">Nan et al. (2013)</a> noted that the subretinal pigment epithelial deposits that are a hallmark of age-related macular degeneration contain both C3b and millimolar levels of zinc. By ultracentrifugation and x-ray scattering, they showed that of C3, C3u, and C3b associated strongly with a zinc concentration over 100 micromol, whereas C3c and C3d associated only weakly. In the presence of zinc, C3 formed soluble oligomers, whereas C3u and C3b precipitated. CFH formed large oligomers with a zinc concentration over 10 micromol. The complex of CFH and C3b lost solubility and was precipitated by zinc in a concentration-dependent manner, thereby inhibiting complement activation. <a href="#47" class="mim-tip-reference" title="Nan, R., Tetchner, S., Rodriguez, E., Pao, P.-J., Gor, J., Lengyel, I., Perkins, S. J. <strong>Zinc-induced self-association of complement C3b and factor H: implications for inflammation and age-related macular degeneration.</strong> J. Biol. Chem. 288: 19197-19210, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23661701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23661701</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23661701[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.M113.476143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23661701">Nan et al. (2013)</a> concluded that zinc-induced precipitation may contribute to the initial development of subretinal pigment epithelial deposits in retina and reduce progression to advanced age-related macular degeneration in higher risk patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23661701" 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 mouse models, <a href="#36" class="mim-tip-reference" title="Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., Lemere, C. A., Selkoe, D. J., Stevens, B. <strong>Complement and microglia mediate early synapse loss in Alzheimer mouse models.</strong> Science 352: 712-716, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27033548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27033548</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27033548[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aad8373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27033548">Hong et al. (2016)</a> showed that complement and microglia mediate synaptic loss early in Alzheimer disease (AD; <a href="/entry/104300">104300</a>). C1q (see <a href="/entry/120550">120550</a>), the initiating protein of the classical complement cascade, was increased and associated with synapses before overt plaque deposition. Inhibition of C1q, C3, or the microglial complement receptor CR3 (CD11b/CD18; see <a href="/entry/600065">600065</a>) reduced the number of phagocytic microglia, as well as the extent of early synapse loss. C1q was necessary for the toxic effects of soluble beta-amyloid (A-beta; <a href="/entry/104760">104760</a>) oligomers on synapses and hippocampal long-term potentiation. Finally, microglia in adult brains engulfed synaptic material in a CR3-dependent process when exposed to soluble A-beta oligomers. Together, these findings suggested that the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27033548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#29" class="mim-tip-reference" title="Fong, K. Y., Botto, M., Walport, M. J., So, A. K. <strong>Genomic organization of human complement component C3.</strong> Genomics 7: 579-586, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387584</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90202-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2387584">Fong et al. (1990)</a> reported that the complete C3 gene is 41 kb long, comprising 41 exons. The beta chain spans 13 kb from exon 1 to exon 16. Exon 16 encodes both alpha and beta chains. The alpha chain is 28 kb long, with 26 exons, including exon 16. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2387584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#66" class="mim-tip-reference" title="Weitkamp, L. R., Johnston, E., Guttormsen, S. A. <strong>Probable genetic linkage between the loci for the Lewis blood group and complement C3.</strong> Cytogenet. Cell Genet. 13: 183-184, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4827488/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4827488</a>] [<a href="https://doi.org/10.1159/000130268" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4827488">Weitkamp et al. (1974)</a> presented evidence that the Lewis blood group locus and the C3 locus are linked. Three independent studies, by <a href="#49" class="mim-tip-reference" title="Ott, J., Schrott, H. G., Goldstein, J. L., Hazzard, W. R., Allen, F. H., Falk, C. T., Motulsky, A. G. <strong>Linkage studies in a large kindred with familial hypercholesterolemia.</strong> Am. J. Hum. Genet. 26: 598-603, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4213615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4213615</a>]" pmid="4213615">Ott et al. (1974)</a>, <a href="#11" class="mim-tip-reference" title="Berg, K., Heiberg, A. <strong>Linkage studies on familial hypercholesterolemia with xanthomatosis: normal lipoprotein markers and the C3 polymorphism.</strong> Cytogenet. Cell Genet. 16: 266-270, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/975887/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">975887</a>] [<a href="https://doi.org/10.1159/000130606" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="975887">Berg and Heiberg (1976)</a> and <a href="#28" class="mim-tip-reference" title="Elston, R. C., Namboodiri, K. K., Go, R. C. P., Siervogel, R. M., Glueck, C. J. <strong>Probable linkage between essential familial hypercholesterolemia and third complement component (C3).</strong> Cytogenet. Cell Genet. 16: 294-297, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/975893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">975893</a>] [<a href="https://doi.org/10.1159/000130613" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="975893">Elston et al. (1976)</a>, strongly suggested loose linkage between familial hypercholesterolemia and C3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=975887+4827488+975893+4213615" 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 the method of somatic cell hybridization, <a href="#69" class="mim-tip-reference" title="Whitehead, A. S., Solomon, E., Chambers, S., Bodmer, W. F., Povey, S., Fey, G. <strong>Assignment of the structural gene for the third component of human complement to chromosome 19.</strong> Proc. Nat. Acad. Sci. 79: 5021-5025, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6956911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6956911</a>] [<a href="https://doi.org/10.1073/pnas.79.16.5021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6956911">Whitehead et al. (1982)</a> assigned the gene for fibroblast-derived C3 to chromosome 19. It was at first unclear whether fibroblast and serum C3 were identical; it was known that fibroblast C1q (<a href="/entry/120560">120560</a>) and serum C1q (<a href="/entry/120550">120550</a>) are different (<a href="#60" class="mim-tip-reference" title="Skok, J., Solomon, E., Reid, K. B. M., Thompson, R. A. <strong>Distinct genes for fibroblast and serum C1q.</strong> Nature 292: 549-551, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6973093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6973093</a>] [<a href="https://doi.org/10.1038/292549a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6973093">Skok et al., 1981</a>). Studies with a C3 probe (<a href="#21" class="mim-tip-reference" title="Davies, K. E., Williamson, R., Ball, S., Sarfarazi, M., Meredith, L., Fey, G., Harper, P. S. <strong>C3 DNA sequence and protein polymorphisms in linkage analysis of myotonic dystrophy. (Abstract)</strong> Cytogenet. Cell Genet. 37: 447 only, 1984."None>Davies et al., 1984</a>) suggested that there was only one C3 gene per haploid chromosome set; no other hybridization was observed with relaxed stringency. Furthermore, no recombination was observed between probe and serum C3 (<a href="#72" class="mim-tip-reference" title="Williamson, R. <strong>Personal Communication.</strong> London, England 8/25/1983."None>Williamson, 1983</a>). Thus, serum and fibroblast C3 almost certainly have the same genetic basis. A specific antihuman C3 monoclonal antibody was used by <a href="#69" class="mim-tip-reference" title="Whitehead, A. S., Solomon, E., Chambers, S., Bodmer, W. F., Povey, S., Fey, G. <strong>Assignment of the structural gene for the third component of human complement to chromosome 19.</strong> Proc. Nat. Acad. Sci. 79: 5021-5025, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6956911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6956911</a>] [<a href="https://doi.org/10.1073/pnas.79.16.5021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6956911">Whitehead et al. (1982)</a> in their mapping studies. The assignment to chromosome 19 was confirmed by use of a unique-sequence human genomic C3 DNA clone as a probe in DNA hybridization experiments with DNA prepared from appropriate human-mouse somatic cell hybrids (<a href="#69" class="mim-tip-reference" title="Whitehead, A. S., Solomon, E., Chambers, S., Bodmer, W. F., Povey, S., Fey, G. <strong>Assignment of the structural gene for the third component of human complement to chromosome 19.</strong> Proc. Nat. Acad. Sci. 79: 5021-5025, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6956911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6956911</a>] [<a href="https://doi.org/10.1073/pnas.79.16.5021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6956911">Whitehead et al., 1982</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6973093+6956911" 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="#56" class="mim-tip-reference" title="Sanders, M. F., Crandall, J., Huey, B., Leung, R., King, M. C. <strong>Possible synteny of LE, SE, and C3. (Abstract)</strong> Cytogenet. Cell Genet. 37: 575 only, 1984."None>Sanders et al. (1984)</a> studied the linkage of polymorphic serum C3 to Lewis (<a href="/entry/618983">618983</a>) and secretor (<a href="/entry/182100">182100</a>) and found low positive lod scores for all 3 linkages. They favored the order SE--C3--LE. <a href="#26" class="mim-tip-reference" title="Eiberg, H., Mohr, J., Nielsen, L. S., Simonsen, N. <strong>Genetics and linkage relationships of the C3 polymorphism: discovery of C3-Se linkage and assignment of LES-C3-DM-Se-PEPD-Lu synteny to chromosome 19.</strong> Clin. Genet. 24: 159-170, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6627719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6627719</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1983.tb02233.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6627719">Eiberg et al. (1983)</a> found linkage of secretor with the serum C3 polymorphism (male lod = 4.35, theta = 0.12). There was suggestive evidence of linkage of secretor with PEPD (male and female lod = 2.41, theta = 0.00) and of C3 with PEPD (male lod = 0.95, theta = 0.17)--independent confirmation of assignment to chromosome 19 where PEPD is known to be by somatic cell studies. What they termed Lewis secretion (LES) was also linked to C3 (male lod = 3.63, theta = 0.04). They suggested that the most likely sequence is LES--C3--DM--(Se-PEPD)--Lu. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6627719" 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="Ball, S., Buckton, K. E., Corney, G., Fey, G., Monteiro, M., Noades, J. E., Pym, B., Robson, E. B., Tippett, P. <strong>Mapping studies with peptidase D (PEPD). (Abstract)</strong> Cytogenet. Cell Genet. 37: 411 only, 1984."None>Ball et al. (1984)</a> regionalized C3 to 19pter-p13.2. <a href="#18" class="mim-tip-reference" title="Brook, J. D., Shaw, D. J., Meredith, L., Bruns, G. A. P., Harper, P. S. <strong>Localisation of genetic markers and orientation of the linkage group on chromosome 19.</strong> Hum. Genet. 68: 282-285, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6595199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6595199</a>] [<a href="https://doi.org/10.1007/BF00292584" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6595199">Brook et al. (1984)</a> assigned the gene to 19pter-p13 and concluded that familial hypercholesterolemia is probably distal to C3 in the pter-p13 segment. <a href="#17" class="mim-tip-reference" title="Brook, J. D., Shaw, D. J., Meredith, A. L., Worwood, M., Cowell, J., Scott, J., Knott, T. J., Litt, M., Bufton, L., Harper, P. S. <strong>A somatic cell hybrid panel for chromosome 19: localization of known genes and RFLPs and orientation of the linkage group. (Abstract)</strong> Cytogenet. Cell Genet. 40: 590-591, 1985."None>Brook et al. (1985)</a> later presented data suggesting that the LDL receptor is proximal to C3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6595199" 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="#43" class="mim-tip-reference" title="Lusis, A. J., Heinzmann, C., Sparkes, R. S., Scott, J., Knott, T. J., Geller, R., Sparkes, M. C., Mohandas, T. <strong>Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI.</strong> Proc. Nat. Acad. Sci. 83: 3929-3933, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3459164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3459164</a>] [<a href="https://doi.org/10.1073/pnas.83.11.3929" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3459164">Lusis et al. (1986)</a> used a reciprocal whole arm translocation between the long arm of 19 and the short arm of chromosome 1 to map APOC1, APOC2, APOE, and GPI to the long arm and LDLR, C3, and PEPD to the short arm. Furthermore, they isolated a single lambda phage that carried both APOC1 and APOE separated by about 6 kb of genomic DNA. Since family studies indicate close linkage of APOE and APOC2, the 3 must be in a cluster on 19q. Judging by the sequence of loci suggested by linkage data (pter--FHC--C3--APOE/APOC2), the location of LDLR is probably 19p13.2-p13.12 and of C3, 19p13.2-p13.11. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3459164" 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>Data on gene frequencies of allelic variants were tabulated by <a href="#55" class="mim-tip-reference" title="Roychoudhury, A. K., Nei, M. <strong>Human Polymorphic Genes: World Distribution.</strong> New York: Oxford Univ. Press (pub.) 1988."None>Roychoudhury and Nei (1988)</a>.</p><p>In a grandmother, mother, and 2 sons, <a href="#70" class="mim-tip-reference" title="Wieme, R. J., Demeulenaere, L. <strong>Genetically determined electrophoretic variant of the human complement component C-prime-3.</strong> Nature 214: 1042-1043, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6059034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6059034</a>] [<a href="https://doi.org/10.1038/2141042a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6059034">Wieme and Demeulenaere (1967)</a> found a double electrophoretic band corresponding apparently to complement component C-prime-3 (as it was then called). By means of high voltage starch gel electrophoresis, <a href="#8" class="mim-tip-reference" title="Azen, E. A., Smithies, O. <strong>Genetic polymorphism of C-prime-3 (beta-1C-globulin) in human serum.</strong> Science 162: 905-907, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4176438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4176438</a>] [<a href="https://doi.org/10.1126/science.162.3856.905" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4176438">Azen and Smithies (1968)</a> also found electrophoretic polymorphism of the third component of complement. This component has many important functions in immune mechanisms. <a href="#5" class="mim-tip-reference" title="Alper, C. A., Propp, R. P. <strong>Genetic polymorphism of the third component of human complement (C-prime-3).</strong> J. Clin. Invest. 47: 2181-2192, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5675433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5675433</a>] [<a href="https://doi.org/10.1172/JCI105904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5675433">Alper and Propp (1968)</a> independently found polymorphism of C3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6059034+5675433+4176438" 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>Complement Component 3 Deficiency</em></strong></p><p>
|
|
<a href="#3" class="mim-tip-reference" title="Alper, C. A., Colten, H. R., Rosen, S. F., Rabson, A. R., MacNab, G. M., Gear, J. S. S. <strong>Homozygous deficiency of C3 in a patient with repeated infections.</strong> Lancet 300: 1179-1181, 1972. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4117597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4117597</a>] [<a href="https://doi.org/10.1016/s0140-6736(72)92598-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4117597">Alper et al. (1972)</a> described an Afrikaner patient with a striking susceptibility to pyogenic infection who was apparently homozygous for C3 deficiency (<a href="/entry/613779">613779</a>). Her C3 levels were one-thousandth or less of normal. Many relatives, including both parents, had approximately half-normal levels. In the patient reported by <a href="#3" class="mim-tip-reference" title="Alper, C. A., Colten, H. R., Rosen, S. F., Rabson, A. R., MacNab, G. M., Gear, J. S. S. <strong>Homozygous deficiency of C3 in a patient with repeated infections.</strong> Lancet 300: 1179-1181, 1972. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4117597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4117597</a>] [<a href="https://doi.org/10.1016/s0140-6736(72)92598-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4117597">Alper et al. (1972)</a>, <a href="#14" class="mim-tip-reference" title="Botto, M., Fong, K. Y., So, A. K., Barlow, R., Routier, R., Morley, B. J., Walport, M. J. <strong>Homozygous hereditary C3 deficiency due to a partial gene deletion.</strong> Proc. Nat. Acad. Sci. 89: 4957-4961, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1350678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1350678</a>] [<a href="https://doi.org/10.1073/pnas.89.11.4957" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1350678">Botto et al. (1992)</a> demonstrated homozygosity for a partial deletion of the C3 gene (<a href="#0004">120700.0004</a>) as the molecular basis of the deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1350678+4117597" 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="#48" class="mim-tip-reference" title="Nilsson, U. R., Nilsson, B., Storm, K.-E., Sjolin-Forsberg, G., Hallgren, R. <strong>Hereditary dysfunction of the third component of complement associated with a systemic lupus erythematosus-like syndrome and meningococcal meningitis.</strong> Arthritis Rheum. 35: 580-586, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1575793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1575793</a>] [<a href="https://doi.org/10.1002/art.1780350516" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1575793">Nilsson et al. (1992)</a> described 3 sisters who were compound heterozygotes for a null allele inherited from the father and a dysfunctional C3 allele inherited from the mother. Alternative pathway complement function was absent, but classic pathway complement function was partially intact. One of the sisters, the proband, had an SLE-like disease. The proband's C3 proved normally susceptible to trypsin proteolysis and partially resistant to classical pathways, but completely resistant to alternative pathway, convertase-dependent cleavage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1575793" 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 22-year-old Japanese male patient with C3 deficiency and an SLE-like, who was born of consanguineous parents, <a href="#63" class="mim-tip-reference" title="Tsukamoto, H., Horiuchi, T., Kokuba, H., Nagae, S., Nishizaka, H., Sawabe, T., Harashima, S., Himeji, D., Koyama, T., Otsuka, J., Mitoma. H., Kimoto, Y., Hashimura, C., Kitano, E., Kitamura, H., Furue, M., Harada, M. <strong>Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus.</strong> Biochem. Biophys. Res. Commun. 330: 298-304, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781264</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.02.159" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781264">Tsukamoto et al. (2005)</a> identified a homozygous splice site mutation (<a href="#0009">120700.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781264" 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>Age-Related Macular Degeneration</em></strong></p><p>
|
|
<a href="#75" class="mim-tip-reference" title="Yates, J. R. W., Sepp, T., Matharu, B. K., Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Hayward, C., Morgan, J., Wright, A. F., Armbrecht, A. M., Dhillon, B., Deary, I. J., Redmond, E., Bird, A. C., Moore, A. T. <strong>Complement C3 variant and the risk of age-related macular degeneration.</strong> New Eng. J. Med. 357: 553-561, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17634448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17634448</a>] [<a href="https://doi.org/10.1056/NEJMoa072618" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17634448">Yates et al. (2007)</a> genotyped SNPs spanning the complement genes C3 and C5 in 603 Caucasian English patients with age-related macular degeneration (ARMD9; <a href="/entry/611378">611378</a>) and 350 controls and found that the common functional R102G polymorphism in the C3 gene (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2230199;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs2230199</a>; <a href="#0001">120700.0001</a>), was strongly associated with ARMD (p = 5.9 x 10(-5)). The association was replicated in a Scottish group of 244 cases and 351 controls (p = 5.0 x 10(-5)). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17634448" 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="#44" class="mim-tip-reference" title="Maller, J. B., Fagerness, J. A., Reynolds, R. C., Neale, B. M., Daly, M. J., Seddon, J. M. <strong>Variation in complement factor 3 is associated with risk of age-related macular degeneration.</strong> Nature Genet. 39: 1200-1201, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17767156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17767156</a>] [<a href="https://doi.org/10.1038/ng2131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17767156">Maller et al. (2007)</a> identified a nonsynonymous coding change in C3 that was strongly associated with risk of age-related macular degeneration in a large case-control sample (p less than 10(-12)). The nonsynonymous coding change (R102G) in the third exon of C3 was the same as that identified by <a href="#75" class="mim-tip-reference" title="Yates, J. R. W., Sepp, T., Matharu, B. K., Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Hayward, C., Morgan, J., Wright, A. F., Armbrecht, A. M., Dhillon, B., Deary, I. J., Redmond, E., Bird, A. C., Moore, A. T. <strong>Complement C3 variant and the risk of age-related macular degeneration.</strong> New Eng. J. Med. 357: 553-561, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17634448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17634448</a>] [<a href="https://doi.org/10.1056/NEJMoa072618" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17634448">Yates et al. (2007)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17634448+17767156" 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="#58" class="mim-tip-reference" title="Seddon, J. M., Yu, Y., Miller, E. C., Reynolds, R., Tan, P. L., Gowrisankar, S., Goldstein, J. I., Triebwasser, M., Anderson, H. E., Zerbib, J., Kavanagh, D., Souied, E., Katsanis, N., Daly, M. J., Atkinson, J. P., Raychaudhuri, S. <strong>Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.</strong> Nature Genet. 45: 1366-1370, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24036952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24036952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24036952[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24036952">Seddon et al. (2013)</a> sequenced the exons of 681 genes within all reported ARMD loci and related pathways in 2,493 cases. <a href="#58" class="mim-tip-reference" title="Seddon, J. M., Yu, Y., Miller, E. C., Reynolds, R., Tan, P. L., Gowrisankar, S., Goldstein, J. I., Triebwasser, M., Anderson, H. E., Zerbib, J., Kavanagh, D., Souied, E., Katsanis, N., Daly, M. J., Atkinson, J. P., Raychaudhuri, S. <strong>Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.</strong> Nature Genet. 45: 1366-1370, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24036952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24036952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24036952[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24036952">Seddon et al. (2013)</a> genotyped 5,115 independent samples and confirmed associations with ARMD of an allele in C3 encoding a lys155-to-gln variant (<a href="#0010">120700.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24036952" 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 Atypical Hemolytic Uremic Syndrome 5</em></strong></p><p>
|
|
In 11 probands with atypical hemolytic uremic syndrome (AHUS5; <a href="/entry/612925">612925</a>), <a href="#31" class="mim-tip-reference" title="Fremeaux-Bacchi, V., Miller, E. C., Liszewski, M. K., Strain, L., Blouin, J., Brown, A. L., Moghal, N., Kaplan, B. S., Weiss, R. A., Lhotta, K., Kapur, G., Mattoo, T., and 14 others. <strong>Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.</strong> Blood 112: 4948-4952, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18796626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18796626</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18796626[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/10.1182/blood-2008-01-133702" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18796626">Fremeaux-Bacchi et al. (2008)</a> identified 9 different mutations in the C3 gene (see, e.g., <a href="#0005">120700.0005</a>-<a href="#0008">120700.0008</a>). Five of the mutations resulted in a gain of function with resistance to degradation by MCP (<a href="/entry/120920">120920</a>) and CFI (<a href="/entry/217030">217030</a>), and 2 resulted in haploinsufficiency. Family history, when available, showed decreased penetrance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18796626" 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="evolution" class="mim-anchor"></a>
|
|
<h4 href="#mimEvolutionFold" id="mimEvolutionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimEvolutionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Evolution</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimEvolutionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Because C3, C4 (<a href="/entry/120810">120810</a>), and C5 (<a href="/entry/120900">120900</a>) are strikingly similar, a common evolutionary origin has been supposed (<a href="#69" class="mim-tip-reference" title="Whitehead, A. S., Solomon, E., Chambers, S., Bodmer, W. F., Povey, S., Fey, G. <strong>Assignment of the structural gene for the third component of human complement to chromosome 19.</strong> Proc. Nat. Acad. Sci. 79: 5021-5025, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6956911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6956911</a>] [<a href="https://doi.org/10.1073/pnas.79.16.5021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6956911">Whitehead et al., 1982</a>). C4 is in the major histocompatibility complex on chromosome 6, but C3 and C5 are not. (In the mouse, both C3 and H2 are on chromosome 17, but not in close proximity. In the chimpanzee, as in man, C2 (<a href="/entry/613927">613927</a>) and Bf are closely linked to the MHC and neither C3 nor C8 (<a href="/entry/120950">120950</a>) is closely linked to MHC. C6 deficiency was observed in the chimpanzee.) The protease alpha-2-macroglobulin (<a href="/entry/103950">103950</a>) also shows considerable homology to C3, suggesting a common evolutionary origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6956911" 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="#41" class="mim-tip-reference" title="Johnson, J. P., McLean, R. H., Cork, L. C., Winkelstein, J. A. <strong>Genetic analysis of an inherited deficiency of the third component of complement in Brittany spaniel dogs.</strong> Am. J. Med. Genet. 25: 557-562, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3789016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3789016</a>] [<a href="https://doi.org/10.1002/ajmg.1320250319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3789016">Johnson et al. (1986)</a> described C3 deficiency in Brittany spaniel dogs. Like the human disorder, this appears to be due to a null gene which apparently is not closely linked to the canine major histocompatibility complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3789016" 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="Circolo, A., Garnier, G., Fukuda, W., Wang, X., Hidvegi, T., Szalai, A. J., Briles, D. E., Volanakis, J. E., Wetsel, R. A., Colten, H. R. <strong>Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA.</strong> Immunopharmacology 42: 135-149, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10408374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10408374</a>] [<a href="https://doi.org/10.1016/s0162-3109(99)00021-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10408374">Circolo et al. (1999)</a> generated C3-deficient mice by disrupting the promoter region and exon 1 of the C3 gene. They detected C3 expression in lung, kidney, heart, spleen, and adipose, but not liver tissue, in these mice. Although pro-C3 could be found in lung tissue, there was no detectable secretion of mature C3. The mutant mice had dramatically decreased resistance to S. pneumoniae. <a href="#20" class="mim-tip-reference" title="Circolo, A., Garnier, G., Fukuda, W., Wang, X., Hidvegi, T., Szalai, A. J., Briles, D. E., Volanakis, J. E., Wetsel, R. A., Colten, H. R. <strong>Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA.</strong> Immunopharmacology 42: 135-149, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10408374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10408374</a>] [<a href="https://doi.org/10.1016/s0162-3109(99)00021-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10408374">Circolo et al. (1999)</a> concluded that this model could be useful for the study of complete C3 deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10408374" 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>Functional impairment of ASP has been hypothesized to be a major cause of hyperapobetalipoproteinemia. However, <a href="#67" class="mim-tip-reference" title="Wetsel, R. A., Kildsgaard, J., Zsigmond E., Liao, W., Chan, L. <strong>Genetic deficiency of acylation stimulating protein (ASP(C3ades-Arg)) does not cause hyperapobetalipoproteinemia in mice.</strong> J. Biol. Chem. 274: 19429-19433, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10383458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10383458</a>] [<a href="https://doi.org/10.1074/jbc.274.27.19429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10383458">Wetsel et al. (1999)</a> could not detect significant differences in lipids or lipoproteins in sera of Asp-deficient mice and wildtype mice. They concluded that Asp deficiency does not cause hyperapobetalipoproteinemia in mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10383458" 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 C3-deficient mice in an allergen-induced model of pulmonary allergy, <a href="#25" class="mim-tip-reference" title="Drouin, S. M., Corry, D. B., Kildsgaard, J., Wetsel, R. A. <strong>Cutting edge: the absence of C3 demonstrates a role for complement in Th2 effector functions in a murine model of pulmonary allergy.</strong> J. Immun. 167: 4141-4145, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591733</a>] [<a href="https://doi.org/10.4049/jimmunol.167.8.4141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11591733">Drouin et al. (2001)</a> showed that these mice had diminished airway hyperresponsiveness and lung eosinophilia. ELISPOT analysis demonstrated reduced numbers of interleukin-4 (IL4; <a href="/entry/147780">147780</a>)-producing cells and attenuated antigen-specific IgE and IgG responses. <a href="#25" class="mim-tip-reference" title="Drouin, S. M., Corry, D. B., Kildsgaard, J., Wetsel, R. A. <strong>Cutting edge: the absence of C3 demonstrates a role for complement in Th2 effector functions in a murine model of pulmonary allergy.</strong> J. Immun. 167: 4141-4145, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591733</a>] [<a href="https://doi.org/10.4049/jimmunol.167.8.4141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11591733">Drouin et al. (2001)</a> concluded that C3 contributes significantly to the pathogenesis of asthma resulting from pulmonary allergy and that complement has a role in the production of IL4, a Th2 cytokine that is critical to the development of airway hyperresponsiveness and IgE responses in asthma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11591733" 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="#50" class="mim-tip-reference" title="Pratt, J. R., Basheer, S. A., Sacks, S. H. <strong>Local synthesis of complement component C3 regulates acute renal transplant rejection.</strong> Nature Med. 8: 582-587, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12042808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12042808</a>] [<a href="https://doi.org/10.1038/nm0602-582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12042808">Pratt et al. (2002)</a> noted that the role of local, as opposed to hepatic, secretion of complement by epithelial and vascular cells is unclear. Proximal tubular epithelial cells (PTECs) synthesize C3 in transplanted kidneys and production by PTECs increases during transplant rejection. <a href="#50" class="mim-tip-reference" title="Pratt, J. R., Basheer, S. A., Sacks, S. H. <strong>Local synthesis of complement component C3 regulates acute renal transplant rejection.</strong> Nature Med. 8: 582-587, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12042808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12042808</a>] [<a href="https://doi.org/10.1038/nm0602-582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12042808">Pratt et al. (2002)</a> found that in mice, wildtype-donor transplanted kidneys were rejected by recipients in 12 days, whereas C3 -/- donor kidneys transplanted into immunocompetent recipients survived for over 100 days. When C3-deficient mice were the recipients, the grafts survived only 16 days, suggesting that locally synthesized rather than circulating C3 has a greater influence on graft rejection. RT-PCR and immunohistochemical analysis indicated that the cortical tubular epithelium is the principal site of C3 expression as well as being the main site of graft inflammation. Stimulation ex vivo of T cells from recipients of C3-null kidneys generated reduced responses in mixed lymphocyte reactions. Interferon-gamma (IFNG; <a href="/entry/147570">147570</a>) treatment of wildtype PTECs enhanced C3 production, but the expression of CD80 (<a href="/entry/112203">112203</a>), CD86 (<a href="/entry/601020">601020</a>), or MHC class II was not different in treated C3-deficient cells. IL2 (<a href="/entry/147680">147680</a>) production was also lower in response to Ifng-treated PTECs from C3 -/- mice. Flow cytometric analysis demonstrated an expanded population of CD4+ Th1-like cells expressing complement receptors CR1 (<a href="/entry/120620">120620</a>) and CR2 (<a href="/entry/120650">120650</a>) in the spleens of the recipients of wildtype kidneys. Immunofluorescence microscopy demonstrated rejecting graft infiltrates containing a similar population of T cells in the peritubular and perivascular regions. <a href="#50" class="mim-tip-reference" title="Pratt, J. R., Basheer, S. A., Sacks, S. H. <strong>Local synthesis of complement component C3 regulates acute renal transplant rejection.</strong> Nature Med. 8: 582-587, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12042808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12042808</a>] [<a href="https://doi.org/10.1038/nm0602-582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12042808">Pratt et al. (2002)</a> concluded that local tissue production of C3 is important in renal graft survival and that rejection is most likely mediated by T cell recognition of C3-tagged graft cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12042808" 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>Acylation-stimulating protein (ASP) is an adipocyte-derived product of C3 cleavage and modification. ASP acts as a paracrine anabolic regulator toward adipose tissue by stimulating glucose uptake and nonesterified fatty acid storage. Genetic deficiency of C3 in mice leads to reduced body fat and decreased leptin (<a href="/entry/164160">164160</a>) levels. Some male mice also show delayed triglyceride clearance. <a href="#74" class="mim-tip-reference" title="Xia, Z., Sniderman, A. D., Cianflone, K. <strong>Acylation-stimulating protein (ASP) deficiency induces obesity resistance and increased energy expenditure in ob/ob mice.</strong> J. Biol. Chem. 277: 45874-45879, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12244109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12244109</a>] [<a href="https://doi.org/10.1074/jbc.M207281200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12244109">Xia et al. (2002)</a> developed C3 and leptin (ob/ob) double-knockout (2KO) mice. Compared with ob/ob mice, 2KO mice had delayed postprandial triglyceride and fatty acid clearance that was associated with decreased body weight and increased insulin sensitivity. Food intake was increased over that of ob/ob mice, but this was balanced by increased energy expenditure as measured by oxygen consumption. Although several metabolic measures were improved relative to ob/ob mice, they were not returned to normal. <a href="#74" class="mim-tip-reference" title="Xia, Z., Sniderman, A. D., Cianflone, K. <strong>Acylation-stimulating protein (ASP) deficiency induces obesity resistance and increased energy expenditure in ob/ob mice.</strong> J. Biol. Chem. 277: 45874-45879, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12244109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12244109</a>] [<a href="https://doi.org/10.1074/jbc.M207281200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12244109">Xia et al. (2002)</a> concluded that the regulation of energy storage by ASP influences energy expenditure and metabolic balance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12244109" 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="#38" class="mim-tip-reference" title="Huber-Lang, M., Sarma, J. V., Zetoune, F. S., Rittirsch, D., Neff, T. A., McGuire, S. R., Lambris, J. D., Warner, R. L., Flierl, M. A., Hoesel, L. M., Gebhard, F., Younger, J. G., Drouin, S. M., Wetsel, R. A., Ward, P. A. <strong>Generation of C5a in the absence of C3: a new complement activation pathway.</strong> Nature Med. 12: 682-687, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16715088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16715088</a>] [<a href="https://doi.org/10.1038/nm1419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16715088">Huber-Lang et al. (2006)</a> found that wildtype mice and C3 -/- mice developed intense lung injury after immune complex deposition, whereas injury was attenuated in C5 (<a href="/entry/120900">120900</a>) -/- mice. Wildtype and C3 -/- mice had similar levels of C5a in bronchoalveolar lavage fluid, and lung injury was attenuated by administration of anti-C5a. Treatment of C3 -/- mice, but not wildtype mice, with antithrombin or the leech anticoagulant hirudin also attenuated lung injury. C3 -/- mice had 3-fold more thrombin (F2; <a href="/entry/176930">176930</a>) activity than wildtype mice, and levels of prothrombin mRNA and protein and thrombin protein in liver were higher than in wildtype mice. Incubation of human C5 with thrombin generated biologically active C5a. <a href="#38" class="mim-tip-reference" title="Huber-Lang, M., Sarma, J. V., Zetoune, F. S., Rittirsch, D., Neff, T. A., McGuire, S. R., Lambris, J. D., Warner, R. L., Flierl, M. A., Hoesel, L. M., Gebhard, F., Younger, J. G., Drouin, S. M., Wetsel, R. A., Ward, P. A. <strong>Generation of C5a in the absence of C3: a new complement activation pathway.</strong> Nature Med. 12: 682-687, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16715088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16715088</a>] [<a href="https://doi.org/10.1038/nm1419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16715088">Huber-Lang et al. (2006)</a> concluded that, in the absence of C3, thrombin substitutes for C3-dependent C5 convertase and that there is linkage between the complement and coagulation pathways to activate complement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16715088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a mouse model of West Nile virus (WNV; see <a href="/entry/610379">610379</a>) neuroinvasive disease, <a href="#64" class="mim-tip-reference" title="Vasek, M. J., Garber, C., Dorsey, D., Durrant, D. M., Bollman, B., Soung, A., Yu, J., Perez-Torres, C., Frouin, A., Wilton, D. K., Funk, K., DeMasters, B. K., and 10 others. <strong>A complement-microglial axis drives synapse loss during virus-induced memory impairment.</strong> Nature 534: 538-543, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27337340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27337340</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27337340[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature18283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27337340">Vasek et al. (2016)</a> showed that viral infection of adult hippocampal neurons induced complement-mediated elimination of presynaptic terminals. In contrast with models using virulent WNV strains, infection of mice with a WNV strain with a mutation in nonstructural protein-5 (NS5) resulted in survival rates and cognitive dysfunction similar to those observed in human WNV neuroinvasive disease. Recovered mice displayed impaired spatial learning and persistence of phagocytic microglia without loss of hippocampal neurons or volume. Hippocampi from recovered mice with poor spatial learning showed increased expression of genes that drive synaptic remodeling by microglia via complement. During WNV neuroinvasive disease, C1qa was upregulated and localized to microglia. Mice with fewer microglia, i.e. Il34 (<a href="/entry/612081">612081</a>) -/- mice, or with deficiency of C3 or C3ar were protected from WNV-induced synaptic terminal loss. <a href="#64" class="mim-tip-reference" title="Vasek, M. J., Garber, C., Dorsey, D., Durrant, D. M., Bollman, B., Soung, A., Yu, J., Perez-Torres, C., Frouin, A., Wilton, D. K., Funk, K., DeMasters, B. K., and 10 others. <strong>A complement-microglial axis drives synapse loss during virus-induced memory impairment.</strong> Nature 534: 538-543, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27337340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27337340</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27337340[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature18283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27337340">Vasek et al. (2016)</a> proposed that C3 and C3ar mediate presynaptic terminal loss in hippocampi of mice exhibiting spatial learning defects during recovery from WNV neuroinvasive disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27337340" 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>10 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/120700" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=120700[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 MACULAR DEGENERATION, AGE-RELATED, 9, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
C3S/C3F POLYMORPHISM
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
C3, ARG102GLY
|
|
</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> rs2230199 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2230199;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/rs2230199?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=rs2230199" 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=rs2230199" 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=RCV000018584 OR RCV000018585 OR RCV000395565 OR RCV001521403 OR RCV002293984 OR RCV002444434" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018584, RCV000018585, RCV000395565, RCV001521403, RCV002293984, RCV002444434" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018584...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#15" class="mim-tip-reference" title="Botto, M., Fong, K. Y., So, A. K., Koch, C., Walport, M. J. <strong>Molecular basis of polymorphisms of human complement component C3.</strong> J. Exp. Med. 172: 1011-1017, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1976733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1976733</a>] [<a href="https://doi.org/10.1084/jem.172.4.1011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1976733">Botto et al. (1990)</a> studied the molecular basis of the C3F versus C3S polymorphism. The less common variant, C3F, occurs with appreciable frequencies (gene frequency = 0.20) only in the Caucasoid populations. <a href="#15" class="mim-tip-reference" title="Botto, M., Fong, K. Y., So, A. K., Koch, C., Walport, M. J. <strong>Molecular basis of polymorphisms of human complement component C3.</strong> J. Exp. Med. 172: 1011-1017, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1976733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1976733</a>] [<a href="https://doi.org/10.1084/jem.172.4.1011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1976733">Botto et al. (1990)</a> found a single-nucleotide change, C to G, at position 364 in exon 3, distinguishing C3S and C3F. This led to a substitution of an arginine residue in C3S for a glycine residue in C3F (R102G). The substitution resulted in a polymorphic restriction site for the enzyme HhaI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1976733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The 3 pathways of complement activation proceed through the cleavage of C3, the most abundant and functionally diverse complement component. The renal tubular epithelium is both an important extrahepatic source of C3 and a major target of immunologic injury during rejection of renal grafts. The donor kidney contributes 5% of the total circulating C3 pool when it is in its stable state but up to 16% during acute rejection. <a href="#19" class="mim-tip-reference" title="Brown, K. M., Kondeatis, E., Vaughan, R. W., Kon, S. P., Farmer, C. K. T., Taylor, J. D., He, X., Johnston, A., Horsfield, C., Janssen, B. J. C., Gros, P., Zhou, W., Sacks, S. H., Sheerin, N. S. <strong>Influence of donor C3 allotype on late renal-transplantation outcome.</strong> New Eng. J. Med. 354: 2014-2123, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16687714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16687714</a>] [<a href="https://doi.org/10.1056/NEJMoa052825" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16687714">Brown et al. (2006)</a> determined the C3 allotypes of 662 pairs of adult kidney donors and recipients and then related C3F/S polymorphism status to demographic and clinical outcome data. Among white C3S/S recipients, receipt of a C3F/F or C3F/S donor kidney, rather than a C3S/S donor kidney, was associated with a significantly better long-term outcome. These findings suggested that the 2 alleles have functional differences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16687714" 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 of 603 Caucasian English patients with age-related macular degeneration (ARMD9; <a href="/entry/611378">611378</a>) and 350 controls, <a href="#75" class="mim-tip-reference" title="Yates, J. R. W., Sepp, T., Matharu, B. K., Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Hayward, C., Morgan, J., Wright, A. F., Armbrecht, A. M., Dhillon, B., Deary, I. J., Redmond, E., Bird, A. C., Moore, A. T. <strong>Complement C3 variant and the risk of age-related macular degeneration.</strong> New Eng. J. Med. 357: 553-561, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17634448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17634448</a>] [<a href="https://doi.org/10.1056/NEJMoa072618" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17634448">Yates et al. (2007)</a> found that the R102G polymorphism, which they referred to as R80G based on numbering that eliminated the 22 residues of the signal peptide, was strongly associated with ARMD (p = 5.9 x 10(-5)). The association was replicated in a Scottish group of 244 cases and 351 controls (p = 5.0 x 10(-5)). The 102R and 102G alleles correspond to slow (C3S) and fast (C3F) electrophoretic variants, respectively. The odds ratio for ARMD in SF heterozygotes and FF homozygotes was 1.7 and 2.6, respectively, compared to SS homozygotes. The estimated population attributable risk for C3F was 22%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17634448" 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="#44" class="mim-tip-reference" title="Maller, J. B., Fagerness, J. A., Reynolds, R. C., Neale, B. M., Daly, M. J., Seddon, J. M. <strong>Variation in complement factor 3 is associated with risk of age-related macular degeneration.</strong> Nature Genet. 39: 1200-1201, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17767156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17767156</a>] [<a href="https://doi.org/10.1038/ng2131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17767156">Maller et al. (2007)</a> also found association of ARMD with R102G in a large case-control sample (P less than 10(-12)). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17767156" 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 matched sample set from the Age-Related Eye Disease Study (AREDS) cohort involving 424 patients with ARMD and 215 patients without ARMD acting as controls, <a href="#13" class="mim-tip-reference" title="Bergeron-Sawitzke, J., Gold, B., Olsh, A., Schlotterbeck, S., Lemon, K., Visvanathan, K., Allikmets, R., Dean, M. <strong>Multilocus analysis of age-related macular degeneration.</strong> Europ. J. Hum. Genet. 17: 1190-1199, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19259132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19259132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19259132[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2009.23" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19259132">Bergeron-Sawitzke et al. (2009)</a> confirmed association between ARMD and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2230199;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs2230199</a>, with both the CG (OR, 1.9; p = 9.0 x 10(-4)) and GG (OR, 2.5; p = 0.03) genotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19259132" 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="#32" class="mim-tip-reference" title="Fritsche, L. G., Chen, W., Schu, M., Yaspan, B. L., Yu, Y., Thorleifsson, G., Zack, D. J., Arakawa, S., Cipriani, V., Ripke, S., Igo, R. P., Jr., Buitendijk, G. H. S., and 144 others. <strong>Seven new loci associated with age-related macular degeneration.</strong> Nature Genet. 45: 433-439, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455636</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455636[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23455636">Fritsche et al. (2013)</a> identified association of the C allele of <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2230199;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs2230199</a> with increased risk of ARMD (OR 1.42, 95% CI 1.37-1.47, combined p = 1 x 10(-41)). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23455636" 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 C3 POLYMORPHISM, HAV 4-1 PLUS/MINUS TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
C3, LEU314PRO
|
|
</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> rs1047286 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1047286;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/rs1047286?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=rs1047286" 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=rs1047286" 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=RCV000018586 OR RCV000286026 OR RCV000321048 OR RCV000380392 OR RCV001515572 OR RCV002293985 OR RCV002371776" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018586, RCV000286026, RCV000321048, RCV000380392, RCV001515572, RCV002293985, RCV002371776" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018586...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#15" class="mim-tip-reference" title="Botto, M., Fong, K. Y., So, A. K., Koch, C., Walport, M. J. <strong>Molecular basis of polymorphisms of human complement component C3.</strong> J. Exp. Med. 172: 1011-1017, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1976733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1976733</a>] [<a href="https://doi.org/10.1084/jem.172.4.1011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1976733">Botto et al. (1990)</a> identified the molecular basis of a structural polymorphism of C3, identified by the monoclonal antibody HAV 4-1: codon 314 in exon 9 of the beta chain showed a change of a proline residue in the HAV 4-1(-) form to a leucine residue in the HAV 4-1(+) form. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1976733" 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 C3 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
C3, 61-BP DEL, EX18
|
|
</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> rs112996548 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs112996548;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/rs112996548?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=rs112996548" 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=rs112996548" 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=RCV000018587" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018587" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018587</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#15" class="mim-tip-reference" title="Botto, M., Fong, K. Y., So, A. K., Koch, C., Walport, M. J. <strong>Molecular basis of polymorphisms of human complement component C3.</strong> J. Exp. Med. 172: 1011-1017, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1976733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1976733</a>] [<a href="https://doi.org/10.1084/jem.172.4.1011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1976733">Botto et al. (1990)</a> studied the DNA from a 10-year-old boy who had suffered from recurrent attacks of otitis media during the first 3 years of life. Between 5 and 8 years of age, he suffered from more than 20 episodes of rash which affected his face, forearms, and hands and resembled the target lesions of erythema multiforme. Attacks were normally preceded by an upper respiratory infection, and a group A beta-hemolytic Streptococcus was isolated from his throat during 2 episodes. The parents were consanguineous ('share a common great-grandparent'). C3 could not be detected by RIA of serum from the patient (<a href="/entry/613779">613779</a>). Segregation of C3S and C3F allotypes within the family confirmed the presence of a null allele, for which the patient was homozygous. DNA studies showed a GT-to-AT mutation at the 5-prime donor splice site of intron 18 of the C3 gene. Exons 17-21 were amplified by PCR from first-strand cDNA synthesized from mRNA obtained from peripheral blood monocytes. This revealed a 61-bp deletion in exon 18, resulting from splicing of a cryptic 5-prime donor splice site in exon 18 with the normal 3-prime splice site in exon 19. The deletion led to a disturbance of the reading frame of the mRNA with a stop codon 17 bp downstream from the abnormal splice in exon 18. Both parents were heterozygous for the C3*Q0 allele (Q0 = quantity zero, i.e., null allele). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1976733" 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 C3 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
C3, 800-BP DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000018588" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018588" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018588</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#14" class="mim-tip-reference" title="Botto, M., Fong, K. Y., So, A. K., Barlow, R., Routier, R., Morley, B. J., Walport, M. J. <strong>Homozygous hereditary C3 deficiency due to a partial gene deletion.</strong> Proc. Nat. Acad. Sci. 89: 4957-4961, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1350678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1350678</a>] [<a href="https://doi.org/10.1073/pnas.89.11.4957" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1350678">Botto et al. (1992)</a> demonstrated partial gene deletion as the molecular basis of C3 deficiency (<a href="/entry/613779">613779</a>) in an Afrikaner patient previously described by <a href="#3" class="mim-tip-reference" title="Alper, C. A., Colten, H. R., Rosen, S. F., Rabson, A. R., MacNab, G. M., Gear, J. S. S. <strong>Homozygous deficiency of C3 in a patient with repeated infections.</strong> Lancet 300: 1179-1181, 1972. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4117597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4117597</a>] [<a href="https://doi.org/10.1016/s0140-6736(72)92598-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4117597">Alper et al. (1972)</a> as homozygous C3 deficient. By Southern blot analysis, they demonstrated that the C3 null gene had an 800-bp deletion in exons 22 and 23, resulting in a frameshift and a stop codon 19 bp downstream from the deletion. DNA sequence analysis showed that the deletion probably arose from homologous recombination between 2 ALU repeats flanking the deletion. This mutant allele was found to have a gene frequency of 0.0057 in the South African Afrikaans-speaking population. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1350678+4117597" 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 HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
C3, ARG570GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909583 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909583;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=rs121909583" 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=rs121909583" 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=RCV000018589 OR RCV001507917 OR RCV001844014 OR RCV002496404 OR RCV004751217" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018589, RCV001507917, RCV001844014, RCV002496404, RCV004751217" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018589...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with atypical hemolytic uremic syndrome (AHUS5; <a href="/entry/612925">612925</a>), <a href="#31" class="mim-tip-reference" title="Fremeaux-Bacchi, V., Miller, E. C., Liszewski, M. K., Strain, L., Blouin, J., Brown, A. L., Moghal, N., Kaplan, B. S., Weiss, R. A., Lhotta, K., Kapur, G., Mattoo, T., and 14 others. <strong>Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.</strong> Blood 112: 4948-4952, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18796626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18796626</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18796626[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/10.1182/blood-2008-01-133702" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18796626">Fremeaux-Bacchi et al. (2008)</a> identified a heterozygous 1775G-A transition in exon 14 of the C3 gene, resulting in an arg570-to-gln (R570Q) substitution. Both patients developed end-stage renal disease and had a total of 5 renal transplants; disease recurred in 1 of the patients after transplant. In vitro functional expression studies showed that binding of the mutant C3 protein to MCP (<a href="/entry/120290">120290</a>) was decreased to 22% of wildtype, which would result in resistance to cleavage by factor I (CFI; <a href="/entry/217030">217030</a>). The mutant C3 also showed reduced binding to factor H (CFH; <a href="/entry/134370">134370</a>) and iC3. The findings indicated that a modification in interactions with regulators results in a secondary gain of function of mutant C3. A third unrelated patient also carried this mutation, which was inherited from her unaffected mother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18796626" 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 HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
C3, ALA1072VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909584 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909584;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=rs121909584" 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=rs121909584" 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=RCV000018590" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018590" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018590</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old girl with atypical hemolytic uremic syndrome-5 (<a href="/entry/612925">612925</a>), <a href="#31" class="mim-tip-reference" title="Fremeaux-Bacchi, V., Miller, E. C., Liszewski, M. K., Strain, L., Blouin, J., Brown, A. L., Moghal, N., Kaplan, B. S., Weiss, R. A., Lhotta, K., Kapur, G., Mattoo, T., and 14 others. <strong>Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.</strong> Blood 112: 4948-4952, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18796626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18796626</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18796626[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/10.1182/blood-2008-01-133702" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18796626">Fremeaux-Bacchi et al. (2008)</a> identified a heterozygous 3281C-T transition in exon 26 of the C3 gene, resulting in an ala1072-to-val (A1072V) substitution. She recovered by age 15 years. Her unaffected father also carried the mutation. In vitro functional expression studies showed that binding of the mutant C3 protein to MCP (<a href="/entry/120290">120290</a>) was decreased to 18% of wildtype, which would result in resistance to cleavage by factor I (CFI; <a href="/entry/217030">217030</a>). The mutant C3 also showed reduced binding to factor H (CFH; <a href="/entry/134370">134370</a>) and iC3. The findings indicated that a modification in interactions with regulators results in a secondary gain of function of mutant C3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18796626" 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 HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
C3, ASP1093ASN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909585 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909585;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=rs121909585" 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=rs121909585" 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=RCV000018591 OR RCV002513105" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018591, RCV002513105" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018591...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 23-year-old woman with atypical hemolytic uremic syndrome (AHUS5; <a href="/entry/612925">612925</a>), <a href="#31" class="mim-tip-reference" title="Fremeaux-Bacchi, V., Miller, E. C., Liszewski, M. K., Strain, L., Blouin, J., Brown, A. L., Moghal, N., Kaplan, B. S., Weiss, R. A., Lhotta, K., Kapur, G., Mattoo, T., and 14 others. <strong>Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.</strong> Blood 112: 4948-4952, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18796626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18796626</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18796626[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/10.1182/blood-2008-01-133702" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18796626">Fremeaux-Bacchi et al. (2008)</a> identified a heterozygous 3343G-A transition in exon 26 of the C3 gene, resulting in an asp1093-to-asn (D1093N) substitution. She had end-stage renal disease and 2 kidney transplants. In vitro functional expression studies showed that binding of the mutant C3 protein to MCP (<a href="/entry/120290">120290</a>) was decreased to 17% of wildtype, which would result in resistance to cleavage by factor I (CFI; <a href="/entry/217030">217030</a>). The mutant C3 also showed reduced binding to factor H (CFH; <a href="/entry/134370">134370</a>) and iC3. The findings indicated that a modification in interactions with regulators results in a secondary gain of function of mutant C3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18796626" 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 HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
C3, TYR832TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909586 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909586;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=rs121909586" 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=rs121909586" 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=RCV000018592" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018592" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018592</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old boy with atypical hemolytic uremic syndrome-5 (<a href="/entry/612925">612925</a>), <a href="#31" class="mim-tip-reference" title="Fremeaux-Bacchi, V., Miller, E. C., Liszewski, M. K., Strain, L., Blouin, J., Brown, A. L., Moghal, N., Kaplan, B. S., Weiss, R. A., Lhotta, K., Kapur, G., Mattoo, T., and 14 others. <strong>Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.</strong> Blood 112: 4948-4952, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18796626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18796626</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18796626[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/10.1182/blood-2008-01-133702" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18796626">Fremeaux-Bacchi et al. (2008)</a> identified a heterozygous 2562C-G transversion in exon 20 of the C3 gene, resulting in a tyr832-to-ter (Y832X) substitution. The patient recovered by age 10 years. His unaffected mother also carried the mutation. The mutation was predicted to result in haploinsufficiency of C3. The authors noted that this finding made the pathogenic mechanism difficult to explain relative to the concept of increased complement activation as the predisposing event in aHUS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18796626" 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 C3 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
C3, IVS38AS, A-G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs111595742 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111595742;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=rs111595742" 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=rs111595742" 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=RCV000018593" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018593" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018593</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 22-year-old Japanese male patient with C3 deficiency (<a href="/entry/613779">613779</a>) and systemic lupus erythematosus, born of consanguineous parents, <a href="#63" class="mim-tip-reference" title="Tsukamoto, H., Horiuchi, T., Kokuba, H., Nagae, S., Nishizaka, H., Sawabe, T., Harashima, S., Himeji, D., Koyama, T., Otsuka, J., Mitoma. H., Kimoto, Y., Hashimura, C., Kitano, E., Kitamura, H., Furue, M., Harada, M. <strong>Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus.</strong> Biochem. Biophys. Res. Commun. 330: 298-304, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781264</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.02.159" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781264">Tsukamoto et al. (2005)</a> identified a homozygous A-to-G transition in the acceptor site of intron 38 of the C3 gene, resulting in skipping of exon 39. Complement assay detected no C3 in serum and only a trace amount of C3 hemolytic activity. Both parents and 2 sibs were heterozygous for the mutation, and all had reduced levels of C3 hemolytic activity. The patient had suffered from photosensitivity, recurrent fever, and facial erythema from childhood. Expression of the mutant cDNA in COS-7 cells resulted retention of the molecule in the ER-Golgi intermediate compartment due to defective secretion. <a href="#63" class="mim-tip-reference" title="Tsukamoto, H., Horiuchi, T., Kokuba, H., Nagae, S., Nishizaka, H., Sawabe, T., Harashima, S., Himeji, D., Koyama, T., Otsuka, J., Mitoma. H., Kimoto, Y., Hashimura, C., Kitano, E., Kitamura, H., Furue, M., Harada, M. <strong>Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus.</strong> Biochem. Biophys. Res. Commun. 330: 298-304, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781264</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.02.159" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781264">Tsukamoto et al. (2005)</a> concluded that SLE or an SLE-like disease is a complication of hereditary homozygous C3 deficiency in Japan. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781264" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MACULAR DEGENERATION, AGE-RELATED, 9, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
C3, LYS155GLN (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs147859257;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs147859257</a>)
|
|
</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> rs147859257 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs147859257;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/rs147859257?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=rs147859257" 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=rs147859257" 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=RCV000077796 OR RCV000202831 OR RCV000765476 OR RCV000963525 OR RCV001130000 OR RCV001130001 OR RCV001130002 OR RCV003915045 OR RCV004814999" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000077796, RCV000202831, RCV000765476, RCV000963525, RCV001130000, RCV001130001, RCV001130002, RCV003915045, RCV004814999" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000077796...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#58" class="mim-tip-reference" title="Seddon, J. M., Yu, Y., Miller, E. C., Reynolds, R., Tan, P. L., Gowrisankar, S., Goldstein, J. I., Triebwasser, M., Anderson, H. E., Zerbib, J., Kavanagh, D., Souied, E., Katsanis, N., Daly, M. J., Atkinson, J. P., Raychaudhuri, S. <strong>Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.</strong> Nature Genet. 45: 1366-1370, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24036952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24036952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24036952[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24036952">Seddon et al. (2013)</a> identified an increased risk of age-related macular degeneration (ARMD9; <a href="/entry/611378">611378</a>) in individuals with a lys155-to-gln (K155Q) variant (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs147859257;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs147859257</a>) with a joint p value of 5.2 x 10(-9) and an odds ratio of 3.8. <a href="#58" class="mim-tip-reference" title="Seddon, J. M., Yu, Y., Miller, E. C., Reynolds, R., Tan, P. L., Gowrisankar, S., Goldstein, J. I., Triebwasser, M., Anderson, H. E., Zerbib, J., Kavanagh, D., Souied, E., Katsanis, N., Daly, M. J., Atkinson, J. P., Raychaudhuri, S. <strong>Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.</strong> Nature Genet. 45: 1366-1370, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24036952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24036952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24036952[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24036952">Seddon et al. (2013)</a> showed that substitution of gln for lys at codon 155 results in resistance to proteolytic inactivation by CFH (<a href="/entry/134370">134370</a>) and CFI (<a href="/entry/217030">217030</a>). They concluded that their results implicated loss of C3 protein regulation and excessive alternative complement activation in ARMD pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24036952" 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>Through whole-genome sequencing of 2,230 Icelanders, <a href="#35" class="mim-tip-reference" title="Helgason, H., Sulem, P., Duvvari, M. R., Luo, H., Thorleifsson, G., Stefansson, H., Jonsdottir, I., Masson, G., Gudbjartsson, D. F., Walters, G. B., Magnusson, O. T., Kong, A., and 25 others. <strong>A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration.</strong> Nature Genet. 45: 1371-1374, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24036950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24036950</a>] [<a href="https://doi.org/10.1038/ng.2740" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24036950">Helgason et al. (2013)</a> detected a rare nonsynonymous SNP with a minor allele frequency of 0.55% in the C3 gene encoding a K155Q substitution which, following imputation into a set of Icelandic cases with ARMD and controls, associated with disease (odds ratio = 3.45; p = 1.1 x 10(-7)). This signal was independent of the common SNPs in C3 encoding P314L (<a href="#0002">120700.0002</a>) and R102G (<a href="#0001">120700.0001</a>) that associate with ARMD. The association of the K155Q variant was replicated in ARMD case-control samples of European ancestry with an odds ratio of 4.22 and a p value of 1.6 x 10(-10), resulting in an odds ratio of 3.65 and a p value of 8.8 x 10(-16) for all studies combined. In vitro studies suggested that the K155Q substitution reduces C3 binding to CFH, potentially creating resistance to inhibition by this factor. This resistance to inhibition in turn was predicted to result in enhanced complement activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24036950" 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="#76" class="mim-tip-reference" title="Zhan, X., Larson, D. E., Wang, C., Koboldt, D. C., Sergeev, Y. V., Fulton, R. S., Fulton, L. L., Fronick, C. C., Branham, K. E., Bragg-Gresham, J., Jun, G., Hu, Y, and 48 others. <strong>Identification of a rare coding variant in complement 3 associated with age-related macular degeneration.</strong> Nature Genet. 45: 1375-1379, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24036949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24036949</a>] [<a href="https://doi.org/10.1038/ng.2758" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24036949">Zhan et al. (2013)</a> sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes) and then augmented their control set with ancestry-matched exome-sequenced controls. An analysis of coding variation in 2,268 ARMD cases and 2,268 ancestry-matched controls identified 2 large-effect rare variants: K155Q encoded in the C3 gene, with a case frequency of 1.06%, control frequency of 0.39%, and odds ratio of 2.68; and R1210C (<a href="/entry/134370#0017">134370.0017</a>) encoded in the CFH gene, with a case frequency of 0.51%, control frequency of 0.02%, and odds ratio of 23.11. The variants suggested decreased inhibition of C3 by CFH, resulting in increased activation of the alternative complement pathway, as a key component of disease biology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24036949" 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="#58" class="mim-tip-reference" title="Seddon, J. M., Yu, Y., Miller, E. C., Reynolds, R., Tan, P. L., Gowrisankar, S., Goldstein, J. I., Triebwasser, M., Anderson, H. E., Zerbib, J., Kavanagh, D., Souied, E., Katsanis, N., Daly, M. J., Atkinson, J. P., Raychaudhuri, S. <strong>Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.</strong> Nature Genet. 45: 1366-1370, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24036952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24036952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24036952[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24036952">Seddon et al. (2013)</a> studied the K155Q allele in the C3 gene, confirming significant association with ARMD in 5,115 independent samples and demonstrating that the Q155 mutant exhibits resistance to proteolytic inactivation by CFH (<a href="/entry/134370">134370</a>) and CFI (<a href="/entry/217030">217030</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24036952" 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="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Alper1976" class="mim-tip-reference" title="Alper, C. A., Colten, H. R., Gear, J. S. S., Rabson, A. R., Rosen, F. S. <strong>Homozygous human C3 deficiency: the role of C3 in antibody production, C1s-induced vasopermeability, and cobra venom-induced passive hemolysis.</strong> J. Clin. Invest. 57: 222-229, 1976.">Alper et al. (1976)</a>; <a href="#Alper1969" class="mim-tip-reference" title="Alper, C. A., Propp, R. P., Klemperer, M. R., Rosen, F. S. <strong>Inherited deficiency of the third component of human complement (C-prime-3).</strong> J. Clin. Invest. 48: 553-557, 1969.">Alper et al. (1969)</a>; <a href="#Alper1971" class="mim-tip-reference" title="Alper, C. A., Rosen, F. S. <strong>Studies of a hypomorphic variant of human C3.</strong> J. Clin. Invest. 50: 324-326, 1971.">Alper and Rosen (1971)</a>; <a href="#Arvilommi1973" class="mim-tip-reference" title="Arvilommi, H., Berg, K., Eriksson, A. W. <strong>C3 types and their inheritance in Finnish Lapps, Maris (Cheremisses) and Greenland Eskimos.</strong> Humangenetik 18: 253-259, 1973.">Arvilommi et al. (1973)</a>; <a href="#Ballow1975" class="mim-tip-reference" title="Ballow, M., Shira, J. E., Harden, L., Yang, S. Y., Day, N. K. <strong>Complete absence of the third component of complement in man.</strong> J. Clin. Invest. 56: 703-710, 1975.">Ballow et al. (1975)</a>; <a href="#Berg1978" class="mim-tip-reference" title="Berg, K., Heiberg, A. <strong>Linkage between familial hypercholesterolemia with xanthomatosis and the C3 polymorphism confirmed.</strong> Cytogenet. Cell Genet. 22: 621-623, 1978.">Berg and Heiberg
|
|
(1978)</a>; <a href="#Botto1990" class="mim-tip-reference" title="Botto, M., Fong, K. Y., So, A. K., Rudge, A., Walport, M. J. <strong>Molecular basis of hereditary C3 deficiency.</strong> J. Clin. Invest. 86: 1158-1163, 1990.">Botto et al. (1990)</a>; <a href="#Donald1984" class="mim-tip-reference" title="Donald, J. A., Ball, S. P. <strong>Approximate linkage equilibrium between two polymorphic sites within the gene for human complement component 3.</strong> Ann. Hum. Genet. 48: 269-273, 1984.">Donald and Ball (1984)</a>; <a href="#Einstein1977" class="mim-tip-reference" title="Einstein, L. P., Hansen, P. J., Ballow, M., Davis, A. E., III, Davis, J. S., IV, Alper, C. A., Rosen, F. S., Colten, H. R. <strong>Biosynthesis of the third component of complement (C3) in vitro by monocytes from both normal and homozygous C3-deficient humans.</strong> J. Clin. Invest. 60: 963-969, 1977.">Einstein et al.
|
|
(1977)</a>; <a href="#Gedde-Dahl1974" class="mim-tip-reference" title="Gedde-Dahl, T., Jr., Teisberg, P., Thorsby, E. <strong>C(3) polymorphism: genetic linkage relations.</strong> Clin. Genet. 6: 66-72, 1974.">Gedde-Dahl et al. (1974)</a>; <a href="#Goedde1970" class="mim-tip-reference" title="Goedde, H. W., Benkmann, H.-G., Hirth, L. <strong>Genetic polymorphism of C-prime-3(beta-1C-globulin) component of complement in a German and a Spanish population.</strong> Humangenetik 10: 231-234, 1970.">Goedde et al. (1970)</a>; <a href="#Hoppe1978" class="mim-tip-reference" title="Hoppe, H. H., Goedde, H. W., Agarwal, D. P., Benkmann, H.-G., Hirth, L., Janssen, W. <strong>A silent (C-prime-3) producing partial deficiency of the third component of human complement.</strong> Hum. Hered. 28: 141-146, 1978.">Hoppe et al.
|
|
(1978)</a>; <a href="#Koch1986" class="mim-tip-reference" title="Koch, C., Behrendt, N. <strong>A novel polymorphism of human complement component C3 detected by means of a monoclonal antibody.</strong> Immunogenetics 23: 322-325, 1986.">Koch and Behrendt (1986)</a>; <a href="#McLean1985" class="mim-tip-reference" title="McLean, R. H., Bryan, R. K., Winkelstein, J. <strong>Hypomorphic variant of the slow allele of C3 associated with hypocomplementemia and hematuria.</strong> Am. J. Med. 78: 865-868, 1985.">McLean et al. (1985)</a>; <a href="#Muller-Eberhard1968" class="mim-tip-reference" title="Muller-Eberhard, H. J. <strong>Chemistry and reaction mechanisms of complement.</strong> Adv. Immun. 8: 1-80, 1968.">Muller-Eberhard (1968)</a>; <a href="#Raum1980" class="mim-tip-reference" title="Raum, D., Donaldson, V. H., Rosen, F. S., Alper, C. A. <strong>Genetics of complement.</strong> Curr. Top. Hemat. 3: 111-174, 1980.">Raum et al. (1980)</a>; <a href="#Raum1980" class="mim-tip-reference" title="Raum, D., Donaldson, V. H., Rosen, F. S., Alper, C. A. <strong>Genetics of complement.</strong> Curr. Top. Hemat. 3: 111-174, 1980.">Raum et al. (1980)</a>; <a href="#Teisberg1970" class="mim-tip-reference" title="Teisberg, P. <strong>New variants in the C3 system.</strong> Hum. Hered. 20: 631-637, 1970.">Teisberg (1970)</a>; <a href="#Teisberg1971" class="mim-tip-reference" title="Teisberg, P. <strong>Another variant in the C3 system.</strong> Clin. Genet. 2: 298-302, 1971.">Teisberg (1971)</a>; <a href="#Walport2001" class="mim-tip-reference" title="Walport, M. J. <strong>Complement (first of two parts).</strong> New Eng. J. Med. 344: 1058-1066, 2001.">Walport (2001)</a>; <a href="#Whitehead1981" class="mim-tip-reference" title="Whitehead, A. S., Sim, R. B., Bodmer, W. F. <strong>A monoclonal antibody against human complement component C3: the production of C3 by human cells in vitro.</strong> Europ. J. Immun. 11: 140-146, 1981.">Whitehead et al.
|
|
(1981)</a>; <a href="#Winkelstein1981" class="mim-tip-reference" title="Winkelstein, J. A., Cork, L. C., Griffin, D. E., Griffin, J. W., Adams, R. J., Price, D. L. <strong>Genetically determined deficiency of the third component of complement in the dog.</strong> Science 212: 1169-1170, 1981.">Winkelstein et al. (1981)</a>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</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="Ajees2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ajees, A. A., Gunasekaran, K., Volanakis, J. E., Narayana, S. V. L., Kotwal, G. J., Krishna Murthy, H. M.
|
|
<strong>The structure of complement C3b provides insights into complement activation and regulation.</strong>
|
|
Nature 444: 221-225, 2006. Note: Retraction: Nature 532: 268 only, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17051152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17051152</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17051152" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature05258" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Alper1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Alper, C. A., Colten, H. R., Gear, J. S. S., Rabson, A. R., Rosen, F. S.
|
|
<strong>Homozygous human C3 deficiency: the role of C3 in antibody production, C1s-induced vasopermeability, and cobra venom-induced passive hemolysis.</strong>
|
|
J. Clin. Invest. 57: 222-229, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1107355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1107355</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1107355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI108263" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Alper1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Alper, C. A., Colten, H. R., Rosen, S. F., Rabson, A. R., MacNab, G. M., Gear, J. S. S.
|
|
<strong>Homozygous deficiency of C3 in a patient with repeated infections.</strong>
|
|
Lancet 300: 1179-1181, 1972. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4117597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4117597</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4117597" 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/s0140-6736(72)92598-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Alper1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Alper, C. A., Propp, R. P., Klemperer, M. R., Rosen, F. S.
|
|
<strong>Inherited deficiency of the third component of human complement (C-prime-3).</strong>
|
|
J. Clin. Invest. 48: 553-557, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5773091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5773091</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5773091" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI106013" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Alper1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Alper, C. A., Propp, R. P.
|
|
<strong>Genetic polymorphism of the third component of human complement (C-prime-3).</strong>
|
|
J. Clin. Invest. 47: 2181-2192, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5675433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5675433</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5675433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI105904" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Alper1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Alper, C. A., Rosen, F. S.
|
|
<strong>Studies of a hypomorphic variant of human C3.</strong>
|
|
J. Clin. Invest. 50: 324-326, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5540171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5540171</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5540171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI106498" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Arvilommi1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Arvilommi, H., Berg, K., Eriksson, A. W.
|
|
<strong>C3 types and their inheritance in Finnish Lapps, Maris (Cheremisses) and Greenland Eskimos.</strong>
|
|
Humangenetik 18: 253-259, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4268949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4268949</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4268949" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00290605" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Azen1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Azen, E. A., Smithies, O.
|
|
<strong>Genetic polymorphism of C-prime-3 (beta-1C-globulin) in human serum.</strong>
|
|
Science 162: 905-907, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4176438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4176438</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4176438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.162.3856.905" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Ball1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ball, S., Buckton, K. E., Corney, G., Fey, G., Monteiro, M., Noades, J. E., Pym, B., Robson, E. B., Tippett, P.
|
|
<strong>Mapping studies with peptidase D (PEPD). (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 411 only, 1984.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Ballow1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ballow, M., Shira, J. E., Harden, L., Yang, S. Y., Day, N. K.
|
|
<strong>Complete absence of the third component of complement in man.</strong>
|
|
J. Clin. Invest. 56: 703-710, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1159084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1159084</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1159084" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI108141" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Berg1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Berg, K., Heiberg, A.
|
|
<strong>Linkage studies on familial hypercholesterolemia with xanthomatosis: normal lipoprotein markers and the C3 polymorphism.</strong>
|
|
Cytogenet. Cell Genet. 16: 266-270, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/975887/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">975887</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=975887" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000130606" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Berg1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Berg, K., Heiberg, A.
|
|
<strong>Linkage between familial hypercholesterolemia with xanthomatosis and the C3 polymorphism confirmed.</strong>
|
|
Cytogenet. Cell Genet. 22: 621-623, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/752554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">752554</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=752554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000131037" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Bergeron-Sawitzke2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bergeron-Sawitzke, J., Gold, B., Olsh, A., Schlotterbeck, S., Lemon, K., Visvanathan, K., Allikmets, R., Dean, M.
|
|
<strong>Multilocus analysis of age-related macular degeneration.</strong>
|
|
Europ. J. Hum. Genet. 17: 1190-1199, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19259132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19259132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19259132[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=19259132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ejhg.2009.23" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Botto1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Botto, M., Fong, K. Y., So, A. K., Barlow, R., Routier, R., Morley, B. J., Walport, M. J.
|
|
<strong>Homozygous hereditary C3 deficiency due to a partial gene deletion.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 4957-4961, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1350678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1350678</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1350678" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.89.11.4957" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Botto1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Botto, M., Fong, K. Y., So, A. K., Koch, C., Walport, M. J.
|
|
<strong>Molecular basis of polymorphisms of human complement component C3.</strong>
|
|
J. Exp. Med. 172: 1011-1017, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1976733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1976733</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1976733" 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.172.4.1011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Botto1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Botto, M., Fong, K. Y., So, A. K., Rudge, A., Walport, M. J.
|
|
<strong>Molecular basis of hereditary C3 deficiency.</strong>
|
|
J. Clin. Invest. 86: 1158-1163, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2212005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2212005</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2212005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI114821" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Brook1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brook, J. D., Shaw, D. J., Meredith, A. L., Worwood, M., Cowell, J., Scott, J., Knott, T. J., Litt, M., Bufton, L., Harper, P. S.
|
|
<strong>A somatic cell hybrid panel for chromosome 19: localization of known genes and RFLPs and orientation of the linkage group. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 40: 590-591, 1985.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Brook1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brook, J. D., Shaw, D. J., Meredith, L., Bruns, G. A. P., Harper, P. S.
|
|
<strong>Localisation of genetic markers and orientation of the linkage group on chromosome 19.</strong>
|
|
Hum. Genet. 68: 282-285, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6595199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6595199</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6595199" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00292584" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Brown2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, K. M., Kondeatis, E., Vaughan, R. W., Kon, S. P., Farmer, C. K. T., Taylor, J. D., He, X., Johnston, A., Horsfield, C., Janssen, B. J. C., Gros, P., Zhou, W., Sacks, S. H., Sheerin, N. S.
|
|
<strong>Influence of donor C3 allotype on late renal-transplantation outcome.</strong>
|
|
New Eng. J. Med. 354: 2014-2123, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16687714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16687714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16687714" 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/NEJMoa052825" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Circolo1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Circolo, A., Garnier, G., Fukuda, W., Wang, X., Hidvegi, T., Szalai, A. J., Briles, D. E., Volanakis, J. E., Wetsel, R. A., Colten, H. R.
|
|
<strong>Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA.</strong>
|
|
Immunopharmacology 42: 135-149, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10408374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10408374</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10408374" 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/s0162-3109(99)00021-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Davies1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davies, K. E., Williamson, R., Ball, S., Sarfarazi, M., Meredith, L., Fey, G., Harper, P. S.
|
|
<strong>C3 DNA sequence and protein polymorphisms in linkage analysis of myotonic dystrophy. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 447 only, 1984.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="de Bruijn1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Bruijn, M. H. L., Fey, G. H.
|
|
<strong>Human complement component C3: cDNA coding sequence and derived primary structure.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 708-712, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2579379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2579379</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2579379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.82.3.708" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Degn2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Degn, S. E., Jensenius, J. C., Thiel, S.
|
|
<strong>Disease-causing mutations in genes of the complement system.</strong>
|
|
Am. J. Hum. Genet. 88: 689-705, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21664996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21664996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21664996[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=21664996" 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.ajhg.2011.05.011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Donald1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Donald, J. A., Ball, S. P.
|
|
<strong>Approximate linkage equilibrium between two polymorphic sites within the gene for human complement component 3.</strong>
|
|
Ann. Hum. Genet. 48: 269-273, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6465843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6465843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6465843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1469-1809.1984.tb01024.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Drouin2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Drouin, S. M., Corry, D. B., Kildsgaard, J., Wetsel, R. A.
|
|
<strong>Cutting edge: the absence of C3 demonstrates a role for complement in Th2 effector functions in a murine model of pulmonary allergy.</strong>
|
|
J. Immun. 167: 4141-4145, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11591733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11591733</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11591733" 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.167.8.4141" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Eiberg1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eiberg, H., Mohr, J., Nielsen, L. S., Simonsen, N.
|
|
<strong>Genetics and linkage relationships of the C3 polymorphism: discovery of C3-Se linkage and assignment of LES-C3-DM-Se-PEPD-Lu synteny to chromosome 19.</strong>
|
|
Clin. Genet. 24: 159-170, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6627719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6627719</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6627719" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1983.tb02233.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Einstein1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Einstein, L. P., Hansen, P. J., Ballow, M., Davis, A. E., III, Davis, J. S., IV, Alper, C. A., Rosen, F. S., Colten, H. R.
|
|
<strong>Biosynthesis of the third component of complement (C3) in vitro by monocytes from both normal and homozygous C3-deficient humans.</strong>
|
|
J. Clin. Invest. 60: 963-969, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/332718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">332718</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=332718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI108876" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Elston1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elston, R. C., Namboodiri, K. K., Go, R. C. P., Siervogel, R. M., Glueck, C. J.
|
|
<strong>Probable linkage between essential familial hypercholesterolemia and third complement component (C3).</strong>
|
|
Cytogenet. Cell Genet. 16: 294-297, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/975893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">975893</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=975893" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000130613" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Fong1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fong, K. Y., Botto, M., Walport, M. J., So, A. K.
|
|
<strong>Genomic organization of human complement component C3.</strong>
|
|
Genomics 7: 579-586, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387584</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2387584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(90)90202-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Forneris2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Forneris, F., Ricklin, D., Wu, J., Tzekou, A., Wallace, R. S., Lambris, J. D., Gros, P.
|
|
<strong>Structures of C3b in complex with factors B and D give insight into complement convertase formation.</strong>
|
|
Science 330: 1816-1820, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21205667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21205667</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21205667[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=21205667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1195821" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Fremeaux-Bacchi2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fremeaux-Bacchi, V., Miller, E. C., Liszewski, M. K., Strain, L., Blouin, J., Brown, A. L., Moghal, N., Kaplan, B. S., Weiss, R. A., Lhotta, K., Kapur, G., Mattoo, T., and 14 others.
|
|
<strong>Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.</strong>
|
|
Blood 112: 4948-4952, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18796626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18796626</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18796626[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=18796626" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2008-01-133702" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Fritsche2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fritsche, L. G., Chen, W., Schu, M., Yaspan, B. L., Yu, Y., Thorleifsson, G., Zack, D. J., Arakawa, S., Cipriani, V., Ripke, S., Igo, R. P., Jr., Buitendijk, G. H. S., and 144 others.
|
|
<strong>Seven new loci associated with age-related macular degeneration.</strong>
|
|
Nature Genet. 45: 433-439, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455636</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455636[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=23455636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng.2578" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Gedde-Dahl1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gedde-Dahl, T., Jr., Teisberg, P., Thorsby, E.
|
|
<strong>C(3) polymorphism: genetic linkage relations.</strong>
|
|
Clin. Genet. 6: 66-72, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4426132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4426132</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4426132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1974.tb00632.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Goedde1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goedde, H. W., Benkmann, H.-G., Hirth, L.
|
|
<strong>Genetic polymorphism of C-prime-3(beta-1C-globulin) component of complement in a German and a Spanish population.</strong>
|
|
Humangenetik 10: 231-234, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4097584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4097584</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4097584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00295785" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Helgason2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Helgason, H., Sulem, P., Duvvari, M. R., Luo, H., Thorleifsson, G., Stefansson, H., Jonsdottir, I., Masson, G., Gudbjartsson, D. F., Walters, G. B., Magnusson, O. T., Kong, A., and 25 others.
|
|
<strong>A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration.</strong>
|
|
Nature Genet. 45: 1371-1374, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24036950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24036950</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24036950" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng.2740" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Hong2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., Lemere, C. A., Selkoe, D. J., Stevens, B.
|
|
<strong>Complement and microglia mediate early synapse loss in Alzheimer mouse models.</strong>
|
|
Science 352: 712-716, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27033548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27033548</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27033548[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=27033548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.aad8373" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Hoppe1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hoppe, H. H., Goedde, H. W., Agarwal, D. P., Benkmann, H.-G., Hirth, L., Janssen, W.
|
|
<strong>A silent (C-prime-3) producing partial deficiency of the third component of human complement.</strong>
|
|
Hum. Hered. 28: 141-146, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/621088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">621088</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=621088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000152954" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Huber-Lang2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huber-Lang, M., Sarma, J. V., Zetoune, F. S., Rittirsch, D., Neff, T. A., McGuire, S. R., Lambris, J. D., Warner, R. L., Flierl, M. A., Hoesel, L. M., Gebhard, F., Younger, J. G., Drouin, S. M., Wetsel, R. A., Ward, P. A.
|
|
<strong>Generation of C5a in the absence of C3: a new complement activation pathway.</strong>
|
|
Nature Med. 12: 682-687, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16715088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16715088</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16715088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nm1419" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Janssen2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Janssen, B. J. C., Christodoulidou, A., McCarthy, A., Lambris, J. D., Gros, P.
|
|
<strong>Structure of C3b reveals conformational changes that underlie complement activity.</strong>
|
|
Nature 444: 213-216, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17051160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17051160</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17051160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature05172" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Janssen2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Janssen, B. J. C., Huizinga, E. G., Raaijmakers, H. C. A., Roos, A., Daha, M. R., Nilsson-Ekdahl, K., Nilsson, B., Gros, P.
|
|
<strong>Structures of complement component C3 provide insights into the function and evolution of immunity.</strong>
|
|
Nature 437: 505-511, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16177781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16177781</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16177781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature04005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Johnson1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnson, J. P., McLean, R. H., Cork, L. C., Winkelstein, J. A.
|
|
<strong>Genetic analysis of an inherited deficiency of the third component of complement in Brittany spaniel dogs.</strong>
|
|
Am. J. Med. Genet. 25: 557-562, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3789016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3789016</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3789016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320250319" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Koch1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koch, C., Behrendt, N.
|
|
<strong>A novel polymorphism of human complement component C3 detected by means of a monoclonal antibody.</strong>
|
|
Immunogenetics 23: 322-325, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3519446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3519446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3519446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00398796" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Lusis1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lusis, A. J., Heinzmann, C., Sparkes, R. S., Scott, J., Knott, T. J., Geller, R., Sparkes, M. C., Mohandas, T.
|
|
<strong>Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI.</strong>
|
|
Proc. Nat. Acad. Sci. 83: 3929-3933, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3459164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3459164</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3459164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.83.11.3929" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Maller2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maller, J. B., Fagerness, J. A., Reynolds, R. C., Neale, B. M., Daly, M. J., Seddon, J. M.
|
|
<strong>Variation in complement factor 3 is associated with risk of age-related macular degeneration.</strong>
|
|
Nature Genet. 39: 1200-1201, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17767156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17767156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17767156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng2131" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="McLean1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McLean, R. H., Bryan, R. K., Winkelstein, J.
|
|
<strong>Hypomorphic variant of the slow allele of C3 associated with hypocomplementemia and hematuria.</strong>
|
|
Am. J. Med. 78: 865-868, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3993666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3993666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3993666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0002-9343(85)90296-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Muller-Eberhard1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muller-Eberhard, H. J.
|
|
<strong>Chemistry and reaction mechanisms of complement.</strong>
|
|
Adv. Immun. 8: 1-80, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4174135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4174135</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4174135" 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/s0065-2776(08)60464-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Nan2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nan, R., Tetchner, S., Rodriguez, E., Pao, P.-J., Gor, J., Lengyel, I., Perkins, S. J.
|
|
<strong>Zinc-induced self-association of complement C3b and factor H: implications for inflammation and age-related macular degeneration.</strong>
|
|
J. Biol. Chem. 288: 19197-19210, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23661701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23661701</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23661701[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=23661701" 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.M113.476143" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Nilsson1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nilsson, U. R., Nilsson, B., Storm, K.-E., Sjolin-Forsberg, G., Hallgren, R.
|
|
<strong>Hereditary dysfunction of the third component of complement associated with a systemic lupus erythematosus-like syndrome and meningococcal meningitis.</strong>
|
|
Arthritis Rheum. 35: 580-586, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1575793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1575793</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1575793" 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/art.1780350516" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Ott1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ott, J., Schrott, H. G., Goldstein, J. L., Hazzard, W. R., Allen, F. H., Falk, C. T., Motulsky, A. G.
|
|
<strong>Linkage studies in a large kindred with familial hypercholesterolemia.</strong>
|
|
Am. J. Hum. Genet. 26: 598-603, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4213615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4213615</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4213615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Pratt2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pratt, J. R., Basheer, S. A., Sacks, S. H.
|
|
<strong>Local synthesis of complement component C3 regulates acute renal transplant rejection.</strong>
|
|
Nature Med. 8: 582-587, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12042808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12042808</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12042808" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nm0602-582" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Rahpeymai2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rahpeymai, Y., Hietala, M. A., Wilhelmsson, U., Fotheringham, A., Davies, I., Nilsson, A.-K., Zwirner, J., Wetsel, R. A., Gerard, C., Pekny, M., Pekna, M.
|
|
<strong>Complement: a novel factor in basal and ischemia-induced neurogenesis.</strong>
|
|
EMBO J. 25: 1364-1374, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16498410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16498410</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16498410[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=16498410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.emboj.7601004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Raum1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raum, D., Balner, H., Petersen, B. H., Alper, C. A.
|
|
<strong>Genetic polymorphism of serum complement components in the chimpanzee.</strong>
|
|
Immunogenetics 10: 455-468, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22457919/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22457919</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22457919" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF01572581" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Raum1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raum, D., Donaldson, V. H., Rosen, F. S., Alper, C. A.
|
|
<strong>Genetics of complement.</strong>
|
|
Curr. Top. Hemat. 3: 111-174, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7035077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7035077</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7035077" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Reis2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reis, E. S., Falcao, D. A., Isaac, L.
|
|
<strong>Clinical aspects and molecular basis of primary deficiencies of complement component C3 and its regulatory proteins factor I and factor H.</strong>
|
|
Scand. J. Immun. 63: 155-168, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16499568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16499568</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16499568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-3083.2006.01729.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Roychoudhury1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Roychoudhury, A. K., Nei, M.
|
|
<strong>Human Polymorphic Genes: World Distribution.</strong>
|
|
New York: Oxford Univ. Press (pub.) 1988.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Sanders1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sanders, M. F., Crandall, J., Huey, B., Leung, R., King, M. C.
|
|
<strong>Possible synteny of LE, SE, and C3. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 575 only, 1984.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Schonthaler2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schonthaler, H. B., Guinea-Viniegra, J., Wculek, S. K., Ruppen, I., Ximenez-Embun, P., Guio-Carrion, A., Navarro, R., Hogg, N., Ashman, K., Wagner, E. F.
|
|
<strong>S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3.</strong>
|
|
Immunity 39: 1171-1181, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24332034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24332034</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24332034" 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.2013.11.011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Seddon2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seddon, J. M., Yu, Y., Miller, E. C., Reynolds, R., Tan, P. L., Gowrisankar, S., Goldstein, J. I., Triebwasser, M., Anderson, H. E., Zerbib, J., Kavanagh, D., Souied, E., Katsanis, N., Daly, M. J., Atkinson, J. P., Raychaudhuri, S.
|
|
<strong>Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.</strong>
|
|
Nature Genet. 45: 1366-1370, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24036952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24036952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24036952[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=24036952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng.2741" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Sivaprasad2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sivaprasad, S., Adewoyin, T., Bailey, T. A., Dandekar, S. S., Jenkins, S., Webster, A. R., Chong, N. V.
|
|
<strong>Estimation of systemic complement C3 activity in age-related macular degeneration.</strong>
|
|
Arch. Ophthal. 125: 515-519, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17420372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17420372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17420372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archopht.125.4.515" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Skok1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Skok, J., Solomon, E., Reid, K. B. M., Thompson, R. A.
|
|
<strong>Distinct genes for fibroblast and serum C1q.</strong>
|
|
Nature 292: 549-551, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6973093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6973093</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6973093" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/292549a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Teisberg1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Teisberg, P.
|
|
<strong>New variants in the C3 system.</strong>
|
|
Hum. Hered. 20: 631-637, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5514302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5514302</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5514302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000152369" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Teisberg1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Teisberg, P.
|
|
<strong>Another variant in the C3 system.</strong>
|
|
Clin. Genet. 2: 298-302, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4112057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4112057</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4112057" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1971.tb00290.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Tsukamoto2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tsukamoto, H., Horiuchi, T., Kokuba, H., Nagae, S., Nishizaka, H., Sawabe, T., Harashima, S., Himeji, D., Koyama, T., Otsuka, J., Mitoma. H., Kimoto, Y., Hashimura, C., Kitano, E., Kitamura, H., Furue, M., Harada, M.
|
|
<strong>Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus.</strong>
|
|
Biochem. Biophys. Res. Commun. 330: 298-304, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781264</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781264" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.bbrc.2005.02.159" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Vasek2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vasek, M. J., Garber, C., Dorsey, D., Durrant, D. M., Bollman, B., Soung, A., Yu, J., Perez-Torres, C., Frouin, A., Wilton, D. K., Funk, K., DeMasters, B. K., and 10 others.
|
|
<strong>A complement-microglial axis drives synapse loss during virus-induced memory impairment.</strong>
|
|
Nature 534: 538-543, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27337340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27337340</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27337340[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=27337340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature18283" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Walport2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Walport, M. J.
|
|
<strong>Complement (first of two parts).</strong>
|
|
New Eng. J. Med. 344: 1058-1066, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11287977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11287977</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11287977" 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/NEJM200104053441406" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Weitkamp1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weitkamp, L. R., Johnston, E., Guttormsen, S. A.
|
|
<strong>Probable genetic linkage between the loci for the Lewis blood group and complement C3.</strong>
|
|
Cytogenet. Cell Genet. 13: 183-184, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4827488/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4827488</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4827488" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000130268" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Wetsel1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wetsel, R. A., Kildsgaard, J., Zsigmond E., Liao, W., Chan, L.
|
|
<strong>Genetic deficiency of acylation stimulating protein (ASP(C3ades-Arg)) does not cause hyperapobetalipoproteinemia in mice.</strong>
|
|
J. Biol. Chem. 274: 19429-19433, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10383458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10383458</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10383458" 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.274.27.19429" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="Whitehead1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Whitehead, A. S., Sim, R. B., Bodmer, W. F.
|
|
<strong>A monoclonal antibody against human complement component C3: the production of C3 by human cells in vitro.</strong>
|
|
Europ. J. Immun. 11: 140-146, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6163641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6163641</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6163641" 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/eji.1830110215" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Whitehead1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Whitehead, A. S., Solomon, E., Chambers, S., Bodmer, W. F., Povey, S., Fey, G.
|
|
<strong>Assignment of the structural gene for the third component of human complement to chromosome 19.</strong>
|
|
Proc. Nat. Acad. Sci. 79: 5021-5025, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6956911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6956911</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6956911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.79.16.5021" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="70" class="mim-anchor"></a>
|
|
<a id="Wieme1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wieme, R. J., Demeulenaere, L.
|
|
<strong>Genetically determined electrophoretic variant of the human complement component C-prime-3.</strong>
|
|
Nature 214: 1042-1043, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6059034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6059034</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6059034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/2141042a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="71" class="mim-anchor"></a>
|
|
<a id="Wiesmann2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wiesmann, C., Katschke, K. J., Jr., Yin, J., Helmy, K. Y., Steffek, M., Fairbrother, W. J., McCallum, S. A., Embuscado, L., DeForge, L., Hass, P. E., van Lookeren Campagne, M.
|
|
<strong>Structure of C3b in complex with CRIg gives insights into regulation of complement activation.</strong>
|
|
Nature 444: 217-220, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17051150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17051150</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17051150" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature05263" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Williamson1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Williamson, R.
|
|
<strong>Personal Communication.</strong>
|
|
London, England 8/25/1983.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Winkelstein1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Winkelstein, J. A., Cork, L. C., Griffin, D. E., Griffin, J. W., Adams, R. J., Price, D. L.
|
|
<strong>Genetically determined deficiency of the third component of complement in the dog.</strong>
|
|
Science 212: 1169-1170, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7233211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7233211</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7233211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.7233211" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Xia2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Xia, Z., Sniderman, A. D., Cianflone, K.
|
|
<strong>Acylation-stimulating protein (ASP) deficiency induces obesity resistance and increased energy expenditure in ob/ob mice.</strong>
|
|
J. Biol. Chem. 277: 45874-45879, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12244109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12244109</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12244109" 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.M207281200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="75" class="mim-anchor"></a>
|
|
<a id="Yates2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yates, J. R. W., Sepp, T., Matharu, B. K., Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Hayward, C., Morgan, J., Wright, A. F., Armbrecht, A. M., Dhillon, B., Deary, I. J., Redmond, E., Bird, A. C., Moore, A. T.
|
|
<strong>Complement C3 variant and the risk of age-related macular degeneration.</strong>
|
|
New Eng. J. Med. 357: 553-561, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17634448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17634448</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17634448" 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/NEJMoa072618" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="76" class="mim-anchor"></a>
|
|
<a id="Zhan2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhan, X., Larson, D. E., Wang, C., Koboldt, D. C., Sergeev, Y. V., Fulton, R. S., Fulton, L. L., Fronick, C. C., Branham, K. E., Bragg-Gresham, J., Jun, G., Hu, Y, and 48 others.
|
|
<strong>Identification of a rare coding variant in complement 3 associated with age-related macular degeneration.</strong>
|
|
Nature Genet. 45: 1375-1379, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24036949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24036949</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24036949" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng.2758" 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 : 09/15/2016
|
|
</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">
|
|
Paul J. Converse - updated : 08/10/2016<br>Paul J. Converse - updated : 11/6/2014<br>Paul J. Converse - updated : 10/7/2014<br>Ada Hamosh - updated : 1/8/2014<br>Ada Hamosh - updated : 10/22/2013<br>Ada Hamosh - updated : 1/28/2011<br>Paul J. Converse - updated : 6/11/2010<br>Paul J. Converse - updated : 5/25/2010<br>Marla J. F. O'Neill - updated : 1/27/2010<br>Jane Kelly - updated : 10/30/2007<br>Victor A. McKusick - updated : 10/18/2007<br>Marla J. F. O'Neill - updated : 8/21/2007<br>Ada Hamosh - updated : 11/28/2006<br>Paul J. Converse - updated : 7/20/2006<br>Victor A. McKusick - updated : 6/22/2006<br>Ada Hamosh - updated : 11/3/2005<br>Patricia A. Hartz - updated : 4/28/2003<br>Paul J. Converse - updated : 5/31/2002<br>Paul J. Converse - updated : 12/11/2001<br>Victor A. McKusick - updated : 4/25/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
mgross : 08/12/2020
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/15/2016<br>mgross : 08/10/2016<br>alopez : 08/03/2016<br>carol : 09/08/2015<br>mgross : 11/7/2014<br>mcolton : 11/6/2014<br>mgross : 10/7/2014<br>alopez : 1/8/2014<br>alopez : 10/22/2013<br>alopez : 8/7/2013<br>carol : 7/6/2012<br>carol : 11/28/2011<br>terry : 5/17/2011<br>carol : 4/25/2011<br>terry : 3/22/2011<br>terry : 3/10/2011<br>carol : 3/1/2011<br>alopez : 2/3/2011<br>alopez : 2/3/2011<br>terry : 1/28/2011<br>mgross : 6/14/2010<br>terry : 6/11/2010<br>wwang : 5/25/2010<br>wwang : 5/25/2010<br>wwang : 1/29/2010<br>terry : 1/27/2010<br>carol : 7/30/2009<br>ckniffin : 7/27/2009<br>terry : 1/13/2009<br>terry : 1/12/2009<br>wwang : 12/27/2007<br>carol : 10/30/2007<br>alopez : 10/23/2007<br>terry : 10/18/2007<br>alopez : 10/4/2007<br>wwang : 8/27/2007<br>terry : 8/21/2007<br>ckniffin : 5/1/2007<br>alopez : 12/7/2006<br>terry : 11/28/2006<br>mgross : 8/7/2006<br>terry : 7/20/2006<br>terry : 6/22/2006<br>alopez : 11/7/2005<br>alopez : 11/7/2005<br>terry : 11/3/2005<br>terry : 5/17/2005<br>carol : 3/17/2004<br>mgross : 2/4/2004<br>terry : 4/28/2003<br>alopez : 5/31/2002<br>alopez : 5/31/2002<br>mgross : 1/9/2002<br>terry : 12/11/2001<br>carol : 4/30/2001<br>mcapotos : 4/26/2001<br>terry : 4/25/2001<br>carol : 8/4/1998<br>dkim : 6/30/1998<br>terry : 11/10/1997<br>mark : 7/30/1995<br>davew : 7/5/1994<br>mimadm : 6/25/1994<br>warfield : 4/8/1994<br>carol : 10/28/1992<br>carol : 8/17/1992
|
|
</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> 120700
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
COMPLEMENT COMPONENT 3; C3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
C3a, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
C3b, INCLUDED<br />
|
|
C3c, INCLUDED<br />
|
|
C3d, INCLUDED<br />
|
|
ACYLATION-STIMULATING PROTEIN, INCLUDED; ASP, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: C3</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 771443008;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 19p13.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 19:6,677,704-6,720,650 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
19p13.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Hemolytic uremic syndrome, atypical, susceptibility to, 5}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
612925
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Macular degeneration, age-related, 9}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
611378
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
C3 deficiency
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613779
|
|
</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 complement system is an important mediator of natural and acquired immunity. It consists of approximately 30 proteins that can exhibit catalytic activity, function as regulators, or act as cellular surface receptors. These components normally circulate in inactive forms and are activated by the classical, alternative, or lectin pathways. Complement component 3 plays a central role in all 3 activation pathways (summary by Reis et al., 2006). </p><p>For a review of the complement system and its components, see Degn et al. (2011). </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>De Bruijn and Fey (1985) presented the complete coding sequence of the C3 gene and the derived amino acid sequence. C3 is an acute phase reactant; increased synthesis of C3 is induced during acute inflammation. The liver is the main site of synthesis, although small amounts are also produced by activated monocytes and macrophages. A single chain precursor (pro-C3) of approximately 200 kD is found intracellularly; the cDNA shows that it comprises 1,663 amino acids. This is processed by proteolytic cleavage into alpha (C3a) and beta (C3b) subunits which in the mature protein are linked by disulfide bonds. Pro-C3 contains a signal peptide of 22 amino acid residues, the beta chain (645 residues) and the alpha chain (992 residues). The 2 chains are joined by 4 arginine residues that are not present in the mature protein. Human C3 has 79% identity to mouse C3 at the nucleotide level and 77% at the amino acid level. </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>
|
|
Janssen et al. (2005) presented the crystal structures of native C3 and its final major proteolytic fragment C3c. The structures revealed 13 domains, 9 of which were unpredicted, and suggested that the proteins of the alpha-2-macroglobulin family evolved from a core of 8 homologous domains. A double mechanism prevents hydrolysis of the thioester group, essential for covalent attachment of activated C3 to target surfaces. Marked conformational changes in the alpha chain, including movement of a critical interaction site through a ring formed by the domains of the beta chain, indicated an unprecedented, conformation-dependent mechanism of activation, regulation, and biologic function of C3. </p><p>Janssen et al. (2006) presented the crystal structure at 4-angstrom resolution of the activated complement protein C3b and described the conformation rearrangements of the 12 domains that take place upon proteolytic activation. In the activated form the thioester is fully exposed for covalent attachment to target surfaces and is more than 85 angstroms away from the buried site in native C3. Marked domain rearrangements in the alpha chain present an altered molecular surface, exposing hidden and cryptic sites that are consistent with known putative binding sites of factor B (CFB; 138470) and several complement regulators. The structural data indicated that the large conformational changes in the proteolytic activation and regulation of C3 take place mainly in the first conversion step, from C3 to C3b. </p><p>Wiesmann et al. (2006) presented the crystal structure of C3b in complex with CRIG (300353) and, using CRIG mutants, provided evidence that CRIG acts as an inhibitor of the alternative pathway of complement. The structure shows that activation of C3 induces major structural rearrangements, including a dramatic movement (greater than 80 angstroms) of the thioester bond-containing domain through which C3b attaches to pathogen surfaces. Wiesmann et al. (2006) showed that CRIG is not only a phagocytic receptor, but also a potent inhibitor of the alternative pathway convertases. Wiesmann et al. (2006) concluded that the structure provides insights into the complex macromolecular structural rearrangements that occur during complement activation and inhibition. </p><p>Forneris et al. (2010) presented crystal structures of the proconvertase C3bB at 4-angstrom resolution and its complex with factor D at 3.5-angstrom resolution. Their data showed how factor B binding to C3b forms an open 'activation' state of C3bB. Factor D specifically binds the open conformation of factor B through a site distant from the catalytic center and is activated by the substrate, which displaces factor D's self-inhibitory loop. This concerted proteolytic mechanism, which if cofactor-dependent and substrate-induced, restricts complement amplification to C3b-tagged target cells. </p><p>The report of Ajees et al. (2006) that presented a structure of C3b was retracted by the journal Nature. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Component C3 plays several important biologic roles in the classical, alternative, and lectin activation pathways, e.g., (1) formation of C3- and C5-convertases, both essential for the full activation of the system; (2) production of opsonins that enhance phagocytosis of microorganisms; (3) degranulation of mast cells and basophils medicated by the fragments C3a and C5a; (4) solubilization and clearance of C3b-bound immune complexes; (5) adjuvant function of fragments C3d and C3dg; and (6) clearance of apoptotic cells (summary by Reis et al., 2006). </p><p>Polymorphisms in complement factor H (CFH; 134370), the main regulator of the activation of C3, have been associated with susceptibility to age-related macular degeneration (see ARMD4, 610698). Sivaprasad et al. (2007) noted that only the C3a des Arg form of C3a is present in human plasma. They therefore studied the levels of C3a des Arg in 84 persons with a clinical diagnosis of ARMD compared with those in age-matched controls. The levels were significantly raised in the patient group compared with those in the control group. Sivaprasad et al. (2007) also found that the concentration of plasma C3a des Arg did not differ significantly between those with different CFH genotypes. The authors suggested that systemic activation of the complement system may contribute to the pathogenesis of ARMD independent of CFH polymorphism. </p><p>By immunofluorescence microscopy, Rahpeymai et al. (2006) demonstrated that mouse neural progenitor cells and immature neurons expressed C3ar (605246) and C5ar (113995). Mice lacking C3 or C3ar, or treated with a C3ar antagonist, show decreased basal neurogenesis and impaired ischemia-induced neurogenesis in the subventricular zone and in the ischemic region. Rahpeymai et al. (2006) concluded that, in the adult mammalian CNS, complement activation products promote both basal and ischemia-induced neurogenesis. </p><p>Using proteomic analysis on human psoriatic epidermis (see 177900), Schonthaler et al. (2013) identified S100A8 (123885) and S100A9 (123886), followed by C3, as the most upregulated proteins specifically expressed in lesional psoriatic skin. Confocal microscopy of human primary keratinocytes treated with TPA (PLAT; 173370) demonstrated a strong increase in nuclear as opposed to cytoplasmic expression of S100A9. Schonthaler et al. (2013) deleted S100a9 in the Jun (165160)/JunB (165161) double-knockout (DKO) mouse model of psoriasis and observed an absence of scaly plaques on the ears and tails, as well as decreased amounts of C3. Inhibition of C3 in DKO mice also strongly reduced inflammatory skin disease. Chromatin immunoprecipitation analysis using DKO cells and S100a9 DKO -/- cells as controls demonstrated binding of S100a9 to the C3 promoter region. Chromatin immunoprecipitation analysis on human keratinocytes also suggested binding of S100A9 to the C3 promoter. Schonthaler et al. (2013) concluded that S100A8/S100A9 regulates C3 at the nuclear level. </p><p>Nan et al. (2013) noted that the subretinal pigment epithelial deposits that are a hallmark of age-related macular degeneration contain both C3b and millimolar levels of zinc. By ultracentrifugation and x-ray scattering, they showed that of C3, C3u, and C3b associated strongly with a zinc concentration over 100 micromol, whereas C3c and C3d associated only weakly. In the presence of zinc, C3 formed soluble oligomers, whereas C3u and C3b precipitated. CFH formed large oligomers with a zinc concentration over 10 micromol. The complex of CFH and C3b lost solubility and was precipitated by zinc in a concentration-dependent manner, thereby inhibiting complement activation. Nan et al. (2013) concluded that zinc-induced precipitation may contribute to the initial development of subretinal pigment epithelial deposits in retina and reduce progression to advanced age-related macular degeneration in higher risk patients. </p><p>Using mouse models, Hong et al. (2016) showed that complement and microglia mediate synaptic loss early in Alzheimer disease (AD; 104300). C1q (see 120550), the initiating protein of the classical complement cascade, was increased and associated with synapses before overt plaque deposition. Inhibition of C1q, C3, or the microglial complement receptor CR3 (CD11b/CD18; see 600065) reduced the number of phagocytic microglia, as well as the extent of early synapse loss. C1q was necessary for the toxic effects of soluble beta-amyloid (A-beta; 104760) oligomers on synapses and hippocampal long-term potentiation. Finally, microglia in adult brains engulfed synaptic material in a CR3-dependent process when exposed to soluble A-beta oligomers. Together, these findings suggested that the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Fong et al. (1990) reported that the complete C3 gene is 41 kb long, comprising 41 exons. The beta chain spans 13 kb from exon 1 to exon 16. Exon 16 encodes both alpha and beta chains. The alpha chain is 28 kb long, with 26 exons, including exon 16. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Weitkamp et al. (1974) presented evidence that the Lewis blood group locus and the C3 locus are linked. Three independent studies, by Ott et al. (1974), Berg and Heiberg (1976) and Elston et al. (1976), strongly suggested loose linkage between familial hypercholesterolemia and C3. </p><p>By the method of somatic cell hybridization, Whitehead et al. (1982) assigned the gene for fibroblast-derived C3 to chromosome 19. It was at first unclear whether fibroblast and serum C3 were identical; it was known that fibroblast C1q (120560) and serum C1q (120550) are different (Skok et al., 1981). Studies with a C3 probe (Davies et al., 1984) suggested that there was only one C3 gene per haploid chromosome set; no other hybridization was observed with relaxed stringency. Furthermore, no recombination was observed between probe and serum C3 (Williamson, 1983). Thus, serum and fibroblast C3 almost certainly have the same genetic basis. A specific antihuman C3 monoclonal antibody was used by Whitehead et al. (1982) in their mapping studies. The assignment to chromosome 19 was confirmed by use of a unique-sequence human genomic C3 DNA clone as a probe in DNA hybridization experiments with DNA prepared from appropriate human-mouse somatic cell hybrids (Whitehead et al., 1982). </p><p>Sanders et al. (1984) studied the linkage of polymorphic serum C3 to Lewis (618983) and secretor (182100) and found low positive lod scores for all 3 linkages. They favored the order SE--C3--LE. Eiberg et al. (1983) found linkage of secretor with the serum C3 polymorphism (male lod = 4.35, theta = 0.12). There was suggestive evidence of linkage of secretor with PEPD (male and female lod = 2.41, theta = 0.00) and of C3 with PEPD (male lod = 0.95, theta = 0.17)--independent confirmation of assignment to chromosome 19 where PEPD is known to be by somatic cell studies. What they termed Lewis secretion (LES) was also linked to C3 (male lod = 3.63, theta = 0.04). They suggested that the most likely sequence is LES--C3--DM--(Se-PEPD)--Lu. </p><p>Ball et al. (1984) regionalized C3 to 19pter-p13.2. Brook et al. (1984) assigned the gene to 19pter-p13 and concluded that familial hypercholesterolemia is probably distal to C3 in the pter-p13 segment. Brook et al. (1985) later presented data suggesting that the LDL receptor is proximal to C3. </p><p>Lusis et al. (1986) used a reciprocal whole arm translocation between the long arm of 19 and the short arm of chromosome 1 to map APOC1, APOC2, APOE, and GPI to the long arm and LDLR, C3, and PEPD to the short arm. Furthermore, they isolated a single lambda phage that carried both APOC1 and APOE separated by about 6 kb of genomic DNA. Since family studies indicate close linkage of APOE and APOC2, the 3 must be in a cluster on 19q. Judging by the sequence of loci suggested by linkage data (pter--FHC--C3--APOE/APOC2), the location of LDLR is probably 19p13.2-p13.12 and of C3, 19p13.2-p13.11. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988).</p><p>In a grandmother, mother, and 2 sons, Wieme and Demeulenaere (1967) found a double electrophoretic band corresponding apparently to complement component C-prime-3 (as it was then called). By means of high voltage starch gel electrophoresis, Azen and Smithies (1968) also found electrophoretic polymorphism of the third component of complement. This component has many important functions in immune mechanisms. Alper and Propp (1968) independently found polymorphism of C3. </p><p><strong><em>Complement Component 3 Deficiency</em></strong></p><p>
|
|
Alper et al. (1972) described an Afrikaner patient with a striking susceptibility to pyogenic infection who was apparently homozygous for C3 deficiency (613779). Her C3 levels were one-thousandth or less of normal. Many relatives, including both parents, had approximately half-normal levels. In the patient reported by Alper et al. (1972), Botto et al. (1992) demonstrated homozygosity for a partial deletion of the C3 gene (120700.0004) as the molecular basis of the deficiency. </p><p>Nilsson et al. (1992) described 3 sisters who were compound heterozygotes for a null allele inherited from the father and a dysfunctional C3 allele inherited from the mother. Alternative pathway complement function was absent, but classic pathway complement function was partially intact. One of the sisters, the proband, had an SLE-like disease. The proband's C3 proved normally susceptible to trypsin proteolysis and partially resistant to classical pathways, but completely resistant to alternative pathway, convertase-dependent cleavage. </p><p>In a 22-year-old Japanese male patient with C3 deficiency and an SLE-like, who was born of consanguineous parents, Tsukamoto et al. (2005) identified a homozygous splice site mutation (120700.0009). </p><p><strong><em>Age-Related Macular Degeneration</em></strong></p><p>
|
|
Yates et al. (2007) genotyped SNPs spanning the complement genes C3 and C5 in 603 Caucasian English patients with age-related macular degeneration (ARMD9; 611378) and 350 controls and found that the common functional R102G polymorphism in the C3 gene (rs2230199; 120700.0001), was strongly associated with ARMD (p = 5.9 x 10(-5)). The association was replicated in a Scottish group of 244 cases and 351 controls (p = 5.0 x 10(-5)). </p><p>Maller et al. (2007) identified a nonsynonymous coding change in C3 that was strongly associated with risk of age-related macular degeneration in a large case-control sample (p less than 10(-12)). The nonsynonymous coding change (R102G) in the third exon of C3 was the same as that identified by Yates et al. (2007). </p><p>Seddon et al. (2013) sequenced the exons of 681 genes within all reported ARMD loci and related pathways in 2,493 cases. Seddon et al. (2013) genotyped 5,115 independent samples and confirmed associations with ARMD of an allele in C3 encoding a lys155-to-gln variant (120700.0010). </p><p><strong><em>Susceptibility to Atypical Hemolytic Uremic Syndrome 5</em></strong></p><p>
|
|
In 11 probands with atypical hemolytic uremic syndrome (AHUS5; 612925), Fremeaux-Bacchi et al. (2008) identified 9 different mutations in the C3 gene (see, e.g., 120700.0005-120700.0008). Five of the mutations resulted in a gain of function with resistance to degradation by MCP (120920) and CFI (217030), and 2 resulted in haploinsufficiency. Family history, when available, showed decreased penetrance. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Evolution</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Because C3, C4 (120810), and C5 (120900) are strikingly similar, a common evolutionary origin has been supposed (Whitehead et al., 1982). C4 is in the major histocompatibility complex on chromosome 6, but C3 and C5 are not. (In the mouse, both C3 and H2 are on chromosome 17, but not in close proximity. In the chimpanzee, as in man, C2 (613927) and Bf are closely linked to the MHC and neither C3 nor C8 (120950) is closely linked to MHC. C6 deficiency was observed in the chimpanzee.) The protease alpha-2-macroglobulin (103950) also shows considerable homology to C3, suggesting a common evolutionary origin. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Johnson et al. (1986) described C3 deficiency in Brittany spaniel dogs. Like the human disorder, this appears to be due to a null gene which apparently is not closely linked to the canine major histocompatibility complex. </p><p>Circolo et al. (1999) generated C3-deficient mice by disrupting the promoter region and exon 1 of the C3 gene. They detected C3 expression in lung, kidney, heart, spleen, and adipose, but not liver tissue, in these mice. Although pro-C3 could be found in lung tissue, there was no detectable secretion of mature C3. The mutant mice had dramatically decreased resistance to S. pneumoniae. Circolo et al. (1999) concluded that this model could be useful for the study of complete C3 deficiency. </p><p>Functional impairment of ASP has been hypothesized to be a major cause of hyperapobetalipoproteinemia. However, Wetsel et al. (1999) could not detect significant differences in lipids or lipoproteins in sera of Asp-deficient mice and wildtype mice. They concluded that Asp deficiency does not cause hyperapobetalipoproteinemia in mice. </p><p>Using C3-deficient mice in an allergen-induced model of pulmonary allergy, Drouin et al. (2001) showed that these mice had diminished airway hyperresponsiveness and lung eosinophilia. ELISPOT analysis demonstrated reduced numbers of interleukin-4 (IL4; 147780)-producing cells and attenuated antigen-specific IgE and IgG responses. Drouin et al. (2001) concluded that C3 contributes significantly to the pathogenesis of asthma resulting from pulmonary allergy and that complement has a role in the production of IL4, a Th2 cytokine that is critical to the development of airway hyperresponsiveness and IgE responses in asthma. </p><p>Pratt et al. (2002) noted that the role of local, as opposed to hepatic, secretion of complement by epithelial and vascular cells is unclear. Proximal tubular epithelial cells (PTECs) synthesize C3 in transplanted kidneys and production by PTECs increases during transplant rejection. Pratt et al. (2002) found that in mice, wildtype-donor transplanted kidneys were rejected by recipients in 12 days, whereas C3 -/- donor kidneys transplanted into immunocompetent recipients survived for over 100 days. When C3-deficient mice were the recipients, the grafts survived only 16 days, suggesting that locally synthesized rather than circulating C3 has a greater influence on graft rejection. RT-PCR and immunohistochemical analysis indicated that the cortical tubular epithelium is the principal site of C3 expression as well as being the main site of graft inflammation. Stimulation ex vivo of T cells from recipients of C3-null kidneys generated reduced responses in mixed lymphocyte reactions. Interferon-gamma (IFNG; 147570) treatment of wildtype PTECs enhanced C3 production, but the expression of CD80 (112203), CD86 (601020), or MHC class II was not different in treated C3-deficient cells. IL2 (147680) production was also lower in response to Ifng-treated PTECs from C3 -/- mice. Flow cytometric analysis demonstrated an expanded population of CD4+ Th1-like cells expressing complement receptors CR1 (120620) and CR2 (120650) in the spleens of the recipients of wildtype kidneys. Immunofluorescence microscopy demonstrated rejecting graft infiltrates containing a similar population of T cells in the peritubular and perivascular regions. Pratt et al. (2002) concluded that local tissue production of C3 is important in renal graft survival and that rejection is most likely mediated by T cell recognition of C3-tagged graft cells. </p><p>Acylation-stimulating protein (ASP) is an adipocyte-derived product of C3 cleavage and modification. ASP acts as a paracrine anabolic regulator toward adipose tissue by stimulating glucose uptake and nonesterified fatty acid storage. Genetic deficiency of C3 in mice leads to reduced body fat and decreased leptin (164160) levels. Some male mice also show delayed triglyceride clearance. Xia et al. (2002) developed C3 and leptin (ob/ob) double-knockout (2KO) mice. Compared with ob/ob mice, 2KO mice had delayed postprandial triglyceride and fatty acid clearance that was associated with decreased body weight and increased insulin sensitivity. Food intake was increased over that of ob/ob mice, but this was balanced by increased energy expenditure as measured by oxygen consumption. Although several metabolic measures were improved relative to ob/ob mice, they were not returned to normal. Xia et al. (2002) concluded that the regulation of energy storage by ASP influences energy expenditure and metabolic balance. </p><p>Huber-Lang et al. (2006) found that wildtype mice and C3 -/- mice developed intense lung injury after immune complex deposition, whereas injury was attenuated in C5 (120900) -/- mice. Wildtype and C3 -/- mice had similar levels of C5a in bronchoalveolar lavage fluid, and lung injury was attenuated by administration of anti-C5a. Treatment of C3 -/- mice, but not wildtype mice, with antithrombin or the leech anticoagulant hirudin also attenuated lung injury. C3 -/- mice had 3-fold more thrombin (F2; 176930) activity than wildtype mice, and levels of prothrombin mRNA and protein and thrombin protein in liver were higher than in wildtype mice. Incubation of human C5 with thrombin generated biologically active C5a. Huber-Lang et al. (2006) concluded that, in the absence of C3, thrombin substitutes for C3-dependent C5 convertase and that there is linkage between the complement and coagulation pathways to activate complement. </p><p>Using a mouse model of West Nile virus (WNV; see 610379) neuroinvasive disease, Vasek et al. (2016) showed that viral infection of adult hippocampal neurons induced complement-mediated elimination of presynaptic terminals. In contrast with models using virulent WNV strains, infection of mice with a WNV strain with a mutation in nonstructural protein-5 (NS5) resulted in survival rates and cognitive dysfunction similar to those observed in human WNV neuroinvasive disease. Recovered mice displayed impaired spatial learning and persistence of phagocytic microglia without loss of hippocampal neurons or volume. Hippocampi from recovered mice with poor spatial learning showed increased expression of genes that drive synaptic remodeling by microglia via complement. During WNV neuroinvasive disease, C1qa was upregulated and localized to microglia. Mice with fewer microglia, i.e. Il34 (612081) -/- mice, or with deficiency of C3 or C3ar were protected from WNV-induced synaptic terminal loss. Vasek et al. (2016) proposed that C3 and C3ar mediate presynaptic terminal loss in hippocampi of mice exhibiting spatial learning defects during recovery from WNV neuroinvasive disease. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>10 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MACULAR DEGENERATION, AGE-RELATED, 9, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
C3S/C3F POLYMORPHISM
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
C3, ARG102GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2230199,
|
|
|
|
|
|
gnomAD: rs2230199,
|
|
|
|
|
|
ClinVar: RCV000018584, RCV000018585, RCV000395565, RCV001521403, RCV002293984, RCV002444434
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Botto et al. (1990) studied the molecular basis of the C3F versus C3S polymorphism. The less common variant, C3F, occurs with appreciable frequencies (gene frequency = 0.20) only in the Caucasoid populations. Botto et al. (1990) found a single-nucleotide change, C to G, at position 364 in exon 3, distinguishing C3S and C3F. This led to a substitution of an arginine residue in C3S for a glycine residue in C3F (R102G). The substitution resulted in a polymorphic restriction site for the enzyme HhaI. </p><p>The 3 pathways of complement activation proceed through the cleavage of C3, the most abundant and functionally diverse complement component. The renal tubular epithelium is both an important extrahepatic source of C3 and a major target of immunologic injury during rejection of renal grafts. The donor kidney contributes 5% of the total circulating C3 pool when it is in its stable state but up to 16% during acute rejection. Brown et al. (2006) determined the C3 allotypes of 662 pairs of adult kidney donors and recipients and then related C3F/S polymorphism status to demographic and clinical outcome data. Among white C3S/S recipients, receipt of a C3F/F or C3F/S donor kidney, rather than a C3S/S donor kidney, was associated with a significantly better long-term outcome. These findings suggested that the 2 alleles have functional differences. </p><p>In a study of 603 Caucasian English patients with age-related macular degeneration (ARMD9; 611378) and 350 controls, Yates et al. (2007) found that the R102G polymorphism, which they referred to as R80G based on numbering that eliminated the 22 residues of the signal peptide, was strongly associated with ARMD (p = 5.9 x 10(-5)). The association was replicated in a Scottish group of 244 cases and 351 controls (p = 5.0 x 10(-5)). The 102R and 102G alleles correspond to slow (C3S) and fast (C3F) electrophoretic variants, respectively. The odds ratio for ARMD in SF heterozygotes and FF homozygotes was 1.7 and 2.6, respectively, compared to SS homozygotes. The estimated population attributable risk for C3F was 22%. </p><p>Maller et al. (2007) also found association of ARMD with R102G in a large case-control sample (P less than 10(-12)). </p><p>In a matched sample set from the Age-Related Eye Disease Study (AREDS) cohort involving 424 patients with ARMD and 215 patients without ARMD acting as controls, Bergeron-Sawitzke et al. (2009) confirmed association between ARMD and rs2230199, with both the CG (OR, 1.9; p = 9.0 x 10(-4)) and GG (OR, 2.5; p = 0.03) genotypes. </p><p>Fritsche et al. (2013) identified association of the C allele of rs2230199 with increased risk of ARMD (OR 1.42, 95% CI 1.37-1.47, combined p = 1 x 10(-41)). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 C3 POLYMORPHISM, HAV 4-1 PLUS/MINUS TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
C3, LEU314PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1047286,
|
|
|
|
|
|
gnomAD: rs1047286,
|
|
|
|
|
|
ClinVar: RCV000018586, RCV000286026, RCV000321048, RCV000380392, RCV001515572, RCV002293985, RCV002371776
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Botto et al. (1990) identified the molecular basis of a structural polymorphism of C3, identified by the monoclonal antibody HAV 4-1: codon 314 in exon 9 of the beta chain showed a change of a proline residue in the HAV 4-1(-) form to a leucine residue in the HAV 4-1(+) form. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 C3 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
C3, 61-BP DEL, EX18
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs112996548,
|
|
|
|
|
|
gnomAD: rs112996548,
|
|
|
|
|
|
ClinVar: RCV000018587
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Botto et al. (1990) studied the DNA from a 10-year-old boy who had suffered from recurrent attacks of otitis media during the first 3 years of life. Between 5 and 8 years of age, he suffered from more than 20 episodes of rash which affected his face, forearms, and hands and resembled the target lesions of erythema multiforme. Attacks were normally preceded by an upper respiratory infection, and a group A beta-hemolytic Streptococcus was isolated from his throat during 2 episodes. The parents were consanguineous ('share a common great-grandparent'). C3 could not be detected by RIA of serum from the patient (613779). Segregation of C3S and C3F allotypes within the family confirmed the presence of a null allele, for which the patient was homozygous. DNA studies showed a GT-to-AT mutation at the 5-prime donor splice site of intron 18 of the C3 gene. Exons 17-21 were amplified by PCR from first-strand cDNA synthesized from mRNA obtained from peripheral blood monocytes. This revealed a 61-bp deletion in exon 18, resulting from splicing of a cryptic 5-prime donor splice site in exon 18 with the normal 3-prime splice site in exon 19. The deletion led to a disturbance of the reading frame of the mRNA with a stop codon 17 bp downstream from the abnormal splice in exon 18. Both parents were heterozygous for the C3*Q0 allele (Q0 = quantity zero, i.e., null allele). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 C3 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
C3, 800-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000018588
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Botto et al. (1992) demonstrated partial gene deletion as the molecular basis of C3 deficiency (613779) in an Afrikaner patient previously described by Alper et al. (1972) as homozygous C3 deficient. By Southern blot analysis, they demonstrated that the C3 null gene had an 800-bp deletion in exons 22 and 23, resulting in a frameshift and a stop codon 19 bp downstream from the deletion. DNA sequence analysis showed that the deletion probably arose from homologous recombination between 2 ALU repeats flanking the deletion. This mutant allele was found to have a gene frequency of 0.0057 in the South African Afrikaans-speaking population. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
C3, ARG570GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909583,
|
|
|
|
|
|
|
|
ClinVar: RCV000018589, RCV001507917, RCV001844014, RCV002496404, RCV004751217
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with atypical hemolytic uremic syndrome (AHUS5; 612925), Fremeaux-Bacchi et al. (2008) identified a heterozygous 1775G-A transition in exon 14 of the C3 gene, resulting in an arg570-to-gln (R570Q) substitution. Both patients developed end-stage renal disease and had a total of 5 renal transplants; disease recurred in 1 of the patients after transplant. In vitro functional expression studies showed that binding of the mutant C3 protein to MCP (120290) was decreased to 22% of wildtype, which would result in resistance to cleavage by factor I (CFI; 217030). The mutant C3 also showed reduced binding to factor H (CFH; 134370) and iC3. The findings indicated that a modification in interactions with regulators results in a secondary gain of function of mutant C3. A third unrelated patient also carried this mutation, which was inherited from her unaffected mother. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
C3, ALA1072VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909584,
|
|
|
|
|
|
|
|
ClinVar: RCV000018590
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old girl with atypical hemolytic uremic syndrome-5 (612925), Fremeaux-Bacchi et al. (2008) identified a heterozygous 3281C-T transition in exon 26 of the C3 gene, resulting in an ala1072-to-val (A1072V) substitution. She recovered by age 15 years. Her unaffected father also carried the mutation. In vitro functional expression studies showed that binding of the mutant C3 protein to MCP (120290) was decreased to 18% of wildtype, which would result in resistance to cleavage by factor I (CFI; 217030). The mutant C3 also showed reduced binding to factor H (CFH; 134370) and iC3. The findings indicated that a modification in interactions with regulators results in a secondary gain of function of mutant C3. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
C3, ASP1093ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909585,
|
|
|
|
|
|
|
|
ClinVar: RCV000018591, RCV002513105
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 23-year-old woman with atypical hemolytic uremic syndrome (AHUS5; 612925), Fremeaux-Bacchi et al. (2008) identified a heterozygous 3343G-A transition in exon 26 of the C3 gene, resulting in an asp1093-to-asn (D1093N) substitution. She had end-stage renal disease and 2 kidney transplants. In vitro functional expression studies showed that binding of the mutant C3 protein to MCP (120290) was decreased to 17% of wildtype, which would result in resistance to cleavage by factor I (CFI; 217030). The mutant C3 also showed reduced binding to factor H (CFH; 134370) and iC3. The findings indicated that a modification in interactions with regulators results in a secondary gain of function of mutant C3. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
C3, TYR832TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909586,
|
|
|
|
|
|
|
|
ClinVar: RCV000018592
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old boy with atypical hemolytic uremic syndrome-5 (612925), Fremeaux-Bacchi et al. (2008) identified a heterozygous 2562C-G transversion in exon 20 of the C3 gene, resulting in a tyr832-to-ter (Y832X) substitution. The patient recovered by age 10 years. His unaffected mother also carried the mutation. The mutation was predicted to result in haploinsufficiency of C3. The authors noted that this finding made the pathogenic mechanism difficult to explain relative to the concept of increased complement activation as the predisposing event in aHUS. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 C3 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
C3, IVS38AS, A-G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111595742,
|
|
|
|
|
|
|
|
ClinVar: RCV000018593
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 22-year-old Japanese male patient with C3 deficiency (613779) and systemic lupus erythematosus, born of consanguineous parents, Tsukamoto et al. (2005) identified a homozygous A-to-G transition in the acceptor site of intron 38 of the C3 gene, resulting in skipping of exon 39. Complement assay detected no C3 in serum and only a trace amount of C3 hemolytic activity. Both parents and 2 sibs were heterozygous for the mutation, and all had reduced levels of C3 hemolytic activity. The patient had suffered from photosensitivity, recurrent fever, and facial erythema from childhood. Expression of the mutant cDNA in COS-7 cells resulted retention of the molecule in the ER-Golgi intermediate compartment due to defective secretion. Tsukamoto et al. (2005) concluded that SLE or an SLE-like disease is a complication of hereditary homozygous C3 deficiency in Japan. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MACULAR DEGENERATION, AGE-RELATED, 9, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
C3, LYS155GLN ({dbSNP rs147859257})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs147859257,
|
|
|
|
|
|
gnomAD: rs147859257,
|
|
|
|
|
|
ClinVar: RCV000077796, RCV000202831, RCV000765476, RCV000963525, RCV001130000, RCV001130001, RCV001130002, RCV003915045, RCV004814999
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Seddon et al. (2013) identified an increased risk of age-related macular degeneration (ARMD9; 611378) in individuals with a lys155-to-gln (K155Q) variant (rs147859257) with a joint p value of 5.2 x 10(-9) and an odds ratio of 3.8. Seddon et al. (2013) showed that substitution of gln for lys at codon 155 results in resistance to proteolytic inactivation by CFH (134370) and CFI (217030). They concluded that their results implicated loss of C3 protein regulation and excessive alternative complement activation in ARMD pathogenesis. </p><p>Through whole-genome sequencing of 2,230 Icelanders, Helgason et al. (2013) detected a rare nonsynonymous SNP with a minor allele frequency of 0.55% in the C3 gene encoding a K155Q substitution which, following imputation into a set of Icelandic cases with ARMD and controls, associated with disease (odds ratio = 3.45; p = 1.1 x 10(-7)). This signal was independent of the common SNPs in C3 encoding P314L (120700.0002) and R102G (120700.0001) that associate with ARMD. The association of the K155Q variant was replicated in ARMD case-control samples of European ancestry with an odds ratio of 4.22 and a p value of 1.6 x 10(-10), resulting in an odds ratio of 3.65 and a p value of 8.8 x 10(-16) for all studies combined. In vitro studies suggested that the K155Q substitution reduces C3 binding to CFH, potentially creating resistance to inhibition by this factor. This resistance to inhibition in turn was predicted to result in enhanced complement activation. </p><p>Zhan et al. (2013) sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes) and then augmented their control set with ancestry-matched exome-sequenced controls. An analysis of coding variation in 2,268 ARMD cases and 2,268 ancestry-matched controls identified 2 large-effect rare variants: K155Q encoded in the C3 gene, with a case frequency of 1.06%, control frequency of 0.39%, and odds ratio of 2.68; and R1210C (134370.0017) encoded in the CFH gene, with a case frequency of 0.51%, control frequency of 0.02%, and odds ratio of 23.11. The variants suggested decreased inhibition of C3 by CFH, resulting in increased activation of the alternative complement pathway, as a key component of disease biology. </p><p>Seddon et al. (2013) studied the K155Q allele in the C3 gene, confirming significant association with ARMD in 5,115 independent samples and demonstrating that the Q155 mutant exhibits resistance to proteolytic inactivation by CFH (134370) and CFI (217030). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Alper et al. (1976); Alper et al. (1969); Alper and Rosen (1971);
|
|
Arvilommi et al. (1973); Ballow et al. (1975); Berg and Heiberg
|
|
(1978); Botto et al. (1990); Donald and Ball (1984); Einstein et al.
|
|
(1977); Gedde-Dahl et al. (1974); Goedde et al. (1970); Hoppe et al.
|
|
(1978); Koch and Behrendt (1986); McLean et al. (1985);
|
|
Muller-Eberhard (1968); Raum et al. (1980); Raum et al. (1980);
|
|
Teisberg (1970); Teisberg (1971); Walport (2001); Whitehead et al.
|
|
(1981); Winkelstein et al. (1981)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ajees, A. A., Gunasekaran, K., Volanakis, J. E., Narayana, S. V. L., Kotwal, G. J., Krishna Murthy, H. M.
|
|
<strong>The structure of complement C3b provides insights into complement activation and regulation.</strong>
|
|
Nature 444: 221-225, 2006. Note: Retraction: Nature 532: 268 only, 2016.
|
|
|
|
|
|
[PubMed: 17051152]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature05258]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Alper, C. A., Colten, H. R., Gear, J. S. S., Rabson, A. R., Rosen, F. S.
|
|
<strong>Homozygous human C3 deficiency: the role of C3 in antibody production, C1s-induced vasopermeability, and cobra venom-induced passive hemolysis.</strong>
|
|
J. Clin. Invest. 57: 222-229, 1976.
|
|
|
|
|
|
[PubMed: 1107355]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI108263]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Alper, C. A., Colten, H. R., Rosen, S. F., Rabson, A. R., MacNab, G. M., Gear, J. S. S.
|
|
<strong>Homozygous deficiency of C3 in a patient with repeated infections.</strong>
|
|
Lancet 300: 1179-1181, 1972. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 4117597]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(72)92598-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Alper, C. A., Propp, R. P., Klemperer, M. R., Rosen, F. S.
|
|
<strong>Inherited deficiency of the third component of human complement (C-prime-3).</strong>
|
|
J. Clin. Invest. 48: 553-557, 1969.
|
|
|
|
|
|
[PubMed: 5773091]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI106013]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Alper, C. A., Propp, R. P.
|
|
<strong>Genetic polymorphism of the third component of human complement (C-prime-3).</strong>
|
|
J. Clin. Invest. 47: 2181-2192, 1968.
|
|
|
|
|
|
[PubMed: 5675433]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI105904]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Alper, C. A., Rosen, F. S.
|
|
<strong>Studies of a hypomorphic variant of human C3.</strong>
|
|
J. Clin. Invest. 50: 324-326, 1971.
|
|
|
|
|
|
[PubMed: 5540171]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI106498]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Arvilommi, H., Berg, K., Eriksson, A. W.
|
|
<strong>C3 types and their inheritance in Finnish Lapps, Maris (Cheremisses) and Greenland Eskimos.</strong>
|
|
Humangenetik 18: 253-259, 1973.
|
|
|
|
|
|
[PubMed: 4268949]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00290605]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Azen, E. A., Smithies, O.
|
|
<strong>Genetic polymorphism of C-prime-3 (beta-1C-globulin) in human serum.</strong>
|
|
Science 162: 905-907, 1968.
|
|
|
|
|
|
[PubMed: 4176438]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.162.3856.905]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ball, S., Buckton, K. E., Corney, G., Fey, G., Monteiro, M., Noades, J. E., Pym, B., Robson, E. B., Tippett, P.
|
|
<strong>Mapping studies with peptidase D (PEPD). (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 411 only, 1984.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ballow, M., Shira, J. E., Harden, L., Yang, S. Y., Day, N. K.
|
|
<strong>Complete absence of the third component of complement in man.</strong>
|
|
J. Clin. Invest. 56: 703-710, 1975.
|
|
|
|
|
|
[PubMed: 1159084]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI108141]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berg, K., Heiberg, A.
|
|
<strong>Linkage studies on familial hypercholesterolemia with xanthomatosis: normal lipoprotein markers and the C3 polymorphism.</strong>
|
|
Cytogenet. Cell Genet. 16: 266-270, 1976.
|
|
|
|
|
|
[PubMed: 975887]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000130606]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berg, K., Heiberg, A.
|
|
<strong>Linkage between familial hypercholesterolemia with xanthomatosis and the C3 polymorphism confirmed.</strong>
|
|
Cytogenet. Cell Genet. 22: 621-623, 1978.
|
|
|
|
|
|
[PubMed: 752554]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000131037]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bergeron-Sawitzke, J., Gold, B., Olsh, A., Schlotterbeck, S., Lemon, K., Visvanathan, K., Allikmets, R., Dean, M.
|
|
<strong>Multilocus analysis of age-related macular degeneration.</strong>
|
|
Europ. J. Hum. Genet. 17: 1190-1199, 2009.
|
|
|
|
|
|
[PubMed: 19259132]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2009.23]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Botto, M., Fong, K. Y., So, A. K., Barlow, R., Routier, R., Morley, B. J., Walport, M. J.
|
|
<strong>Homozygous hereditary C3 deficiency due to a partial gene deletion.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 4957-4961, 1992.
|
|
|
|
|
|
[PubMed: 1350678]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.89.11.4957]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Botto, M., Fong, K. Y., So, A. K., Koch, C., Walport, M. J.
|
|
<strong>Molecular basis of polymorphisms of human complement component C3.</strong>
|
|
J. Exp. Med. 172: 1011-1017, 1990.
|
|
|
|
|
|
[PubMed: 1976733]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.172.4.1011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Botto, M., Fong, K. Y., So, A. K., Rudge, A., Walport, M. J.
|
|
<strong>Molecular basis of hereditary C3 deficiency.</strong>
|
|
J. Clin. Invest. 86: 1158-1163, 1990.
|
|
|
|
|
|
[PubMed: 2212005]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI114821]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brook, J. D., Shaw, D. J., Meredith, A. L., Worwood, M., Cowell, J., Scott, J., Knott, T. J., Litt, M., Bufton, L., Harper, P. S.
|
|
<strong>A somatic cell hybrid panel for chromosome 19: localization of known genes and RFLPs and orientation of the linkage group. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 40: 590-591, 1985.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brook, J. D., Shaw, D. J., Meredith, L., Bruns, G. A. P., Harper, P. S.
|
|
<strong>Localisation of genetic markers and orientation of the linkage group on chromosome 19.</strong>
|
|
Hum. Genet. 68: 282-285, 1984.
|
|
|
|
|
|
[PubMed: 6595199]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00292584]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, K. M., Kondeatis, E., Vaughan, R. W., Kon, S. P., Farmer, C. K. T., Taylor, J. D., He, X., Johnston, A., Horsfield, C., Janssen, B. J. C., Gros, P., Zhou, W., Sacks, S. H., Sheerin, N. S.
|
|
<strong>Influence of donor C3 allotype on late renal-transplantation outcome.</strong>
|
|
New Eng. J. Med. 354: 2014-2123, 2006.
|
|
|
|
|
|
[PubMed: 16687714]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa052825]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Circolo, A., Garnier, G., Fukuda, W., Wang, X., Hidvegi, T., Szalai, A. J., Briles, D. E., Volanakis, J. E., Wetsel, R. A., Colten, H. R.
|
|
<strong>Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA.</strong>
|
|
Immunopharmacology 42: 135-149, 1999.
|
|
|
|
|
|
[PubMed: 10408374]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0162-3109(99)00021-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davies, K. E., Williamson, R., Ball, S., Sarfarazi, M., Meredith, L., Fey, G., Harper, P. S.
|
|
<strong>C3 DNA sequence and protein polymorphisms in linkage analysis of myotonic dystrophy. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 447 only, 1984.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Bruijn, M. H. L., Fey, G. H.
|
|
<strong>Human complement component C3: cDNA coding sequence and derived primary structure.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 708-712, 1985.
|
|
|
|
|
|
[PubMed: 2579379]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.82.3.708]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Degn, S. E., Jensenius, J. C., Thiel, S.
|
|
<strong>Disease-causing mutations in genes of the complement system.</strong>
|
|
Am. J. Hum. Genet. 88: 689-705, 2011.
|
|
|
|
|
|
[PubMed: 21664996]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2011.05.011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donald, J. A., Ball, S. P.
|
|
<strong>Approximate linkage equilibrium between two polymorphic sites within the gene for human complement component 3.</strong>
|
|
Ann. Hum. Genet. 48: 269-273, 1984.
|
|
|
|
|
|
[PubMed: 6465843]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1469-1809.1984.tb01024.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Drouin, S. M., Corry, D. B., Kildsgaard, J., Wetsel, R. A.
|
|
<strong>Cutting edge: the absence of C3 demonstrates a role for complement in Th2 effector functions in a murine model of pulmonary allergy.</strong>
|
|
J. Immun. 167: 4141-4145, 2001.
|
|
|
|
|
|
[PubMed: 11591733]
|
|
|
|
|
|
[Full Text: https://doi.org/10.4049/jimmunol.167.8.4141]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eiberg, H., Mohr, J., Nielsen, L. S., Simonsen, N.
|
|
<strong>Genetics and linkage relationships of the C3 polymorphism: discovery of C3-Se linkage and assignment of LES-C3-DM-Se-PEPD-Lu synteny to chromosome 19.</strong>
|
|
Clin. Genet. 24: 159-170, 1983.
|
|
|
|
|
|
[PubMed: 6627719]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1983.tb02233.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Einstein, L. P., Hansen, P. J., Ballow, M., Davis, A. E., III, Davis, J. S., IV, Alper, C. A., Rosen, F. S., Colten, H. R.
|
|
<strong>Biosynthesis of the third component of complement (C3) in vitro by monocytes from both normal and homozygous C3-deficient humans.</strong>
|
|
J. Clin. Invest. 60: 963-969, 1977.
|
|
|
|
|
|
[PubMed: 332718]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI108876]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elston, R. C., Namboodiri, K. K., Go, R. C. P., Siervogel, R. M., Glueck, C. J.
|
|
<strong>Probable linkage between essential familial hypercholesterolemia and third complement component (C3).</strong>
|
|
Cytogenet. Cell Genet. 16: 294-297, 1976.
|
|
|
|
|
|
[PubMed: 975893]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000130613]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fong, K. Y., Botto, M., Walport, M. J., So, A. K.
|
|
<strong>Genomic organization of human complement component C3.</strong>
|
|
Genomics 7: 579-586, 1990.
|
|
|
|
|
|
[PubMed: 2387584]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90202-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Forneris, F., Ricklin, D., Wu, J., Tzekou, A., Wallace, R. S., Lambris, J. D., Gros, P.
|
|
<strong>Structures of C3b in complex with factors B and D give insight into complement convertase formation.</strong>
|
|
Science 330: 1816-1820, 2010.
|
|
|
|
|
|
[PubMed: 21205667]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1195821]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fremeaux-Bacchi, V., Miller, E. C., Liszewski, M. K., Strain, L., Blouin, J., Brown, A. L., Moghal, N., Kaplan, B. S., Weiss, R. A., Lhotta, K., Kapur, G., Mattoo, T., and 14 others.
|
|
<strong>Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.</strong>
|
|
Blood 112: 4948-4952, 2008.
|
|
|
|
|
|
[PubMed: 18796626]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2008-01-133702]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fritsche, L. G., Chen, W., Schu, M., Yaspan, B. L., Yu, Y., Thorleifsson, G., Zack, D. J., Arakawa, S., Cipriani, V., Ripke, S., Igo, R. P., Jr., Buitendijk, G. H. S., and 144 others.
|
|
<strong>Seven new loci associated with age-related macular degeneration.</strong>
|
|
Nature Genet. 45: 433-439, 2013.
|
|
|
|
|
|
[PubMed: 23455636]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.2578]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gedde-Dahl, T., Jr., Teisberg, P., Thorsby, E.
|
|
<strong>C(3) polymorphism: genetic linkage relations.</strong>
|
|
Clin. Genet. 6: 66-72, 1974.
|
|
|
|
|
|
[PubMed: 4426132]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1974.tb00632.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goedde, H. W., Benkmann, H.-G., Hirth, L.
|
|
<strong>Genetic polymorphism of C-prime-3(beta-1C-globulin) component of complement in a German and a Spanish population.</strong>
|
|
Humangenetik 10: 231-234, 1970.
|
|
|
|
|
|
[PubMed: 4097584]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00295785]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Helgason, H., Sulem, P., Duvvari, M. R., Luo, H., Thorleifsson, G., Stefansson, H., Jonsdottir, I., Masson, G., Gudbjartsson, D. F., Walters, G. B., Magnusson, O. T., Kong, A., and 25 others.
|
|
<strong>A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration.</strong>
|
|
Nature Genet. 45: 1371-1374, 2013.
|
|
|
|
|
|
[PubMed: 24036950]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.2740]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., Lemere, C. A., Selkoe, D. J., Stevens, B.
|
|
<strong>Complement and microglia mediate early synapse loss in Alzheimer mouse models.</strong>
|
|
Science 352: 712-716, 2016.
|
|
|
|
|
|
[PubMed: 27033548]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.aad8373]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoppe, H. H., Goedde, H. W., Agarwal, D. P., Benkmann, H.-G., Hirth, L., Janssen, W.
|
|
<strong>A silent (C-prime-3) producing partial deficiency of the third component of human complement.</strong>
|
|
Hum. Hered. 28: 141-146, 1978.
|
|
|
|
|
|
[PubMed: 621088]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000152954]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huber-Lang, M., Sarma, J. V., Zetoune, F. S., Rittirsch, D., Neff, T. A., McGuire, S. R., Lambris, J. D., Warner, R. L., Flierl, M. A., Hoesel, L. M., Gebhard, F., Younger, J. G., Drouin, S. M., Wetsel, R. A., Ward, P. A.
|
|
<strong>Generation of C5a in the absence of C3: a new complement activation pathway.</strong>
|
|
Nature Med. 12: 682-687, 2006.
|
|
|
|
|
|
[PubMed: 16715088]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm1419]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Janssen, B. J. C., Christodoulidou, A., McCarthy, A., Lambris, J. D., Gros, P.
|
|
<strong>Structure of C3b reveals conformational changes that underlie complement activity.</strong>
|
|
Nature 444: 213-216, 2006.
|
|
|
|
|
|
[PubMed: 17051160]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature05172]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Janssen, B. J. C., Huizinga, E. G., Raaijmakers, H. C. A., Roos, A., Daha, M. R., Nilsson-Ekdahl, K., Nilsson, B., Gros, P.
|
|
<strong>Structures of complement component C3 provide insights into the function and evolution of immunity.</strong>
|
|
Nature 437: 505-511, 2005.
|
|
|
|
|
|
[PubMed: 16177781]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature04005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnson, J. P., McLean, R. H., Cork, L. C., Winkelstein, J. A.
|
|
<strong>Genetic analysis of an inherited deficiency of the third component of complement in Brittany spaniel dogs.</strong>
|
|
Am. J. Med. Genet. 25: 557-562, 1986.
|
|
|
|
|
|
[PubMed: 3789016]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320250319]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koch, C., Behrendt, N.
|
|
<strong>A novel polymorphism of human complement component C3 detected by means of a monoclonal antibody.</strong>
|
|
Immunogenetics 23: 322-325, 1986.
|
|
|
|
|
|
[PubMed: 3519446]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00398796]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lusis, A. J., Heinzmann, C., Sparkes, R. S., Scott, J., Knott, T. J., Geller, R., Sparkes, M. C., Mohandas, T.
|
|
<strong>Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI.</strong>
|
|
Proc. Nat. Acad. Sci. 83: 3929-3933, 1986.
|
|
|
|
|
|
[PubMed: 3459164]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.83.11.3929]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maller, J. B., Fagerness, J. A., Reynolds, R. C., Neale, B. M., Daly, M. J., Seddon, J. M.
|
|
<strong>Variation in complement factor 3 is associated with risk of age-related macular degeneration.</strong>
|
|
Nature Genet. 39: 1200-1201, 2007.
|
|
|
|
|
|
[PubMed: 17767156]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng2131]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McLean, R. H., Bryan, R. K., Winkelstein, J.
|
|
<strong>Hypomorphic variant of the slow allele of C3 associated with hypocomplementemia and hematuria.</strong>
|
|
Am. J. Med. 78: 865-868, 1985.
|
|
|
|
|
|
[PubMed: 3993666]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(85)90296-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muller-Eberhard, H. J.
|
|
<strong>Chemistry and reaction mechanisms of complement.</strong>
|
|
Adv. Immun. 8: 1-80, 1968.
|
|
|
|
|
|
[PubMed: 4174135]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0065-2776(08)60464-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nan, R., Tetchner, S., Rodriguez, E., Pao, P.-J., Gor, J., Lengyel, I., Perkins, S. J.
|
|
<strong>Zinc-induced self-association of complement C3b and factor H: implications for inflammation and age-related macular degeneration.</strong>
|
|
J. Biol. Chem. 288: 19197-19210, 2013.
|
|
|
|
|
|
[PubMed: 23661701]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M113.476143]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nilsson, U. R., Nilsson, B., Storm, K.-E., Sjolin-Forsberg, G., Hallgren, R.
|
|
<strong>Hereditary dysfunction of the third component of complement associated with a systemic lupus erythematosus-like syndrome and meningococcal meningitis.</strong>
|
|
Arthritis Rheum. 35: 580-586, 1992.
|
|
|
|
|
|
[PubMed: 1575793]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/art.1780350516]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ott, J., Schrott, H. G., Goldstein, J. L., Hazzard, W. R., Allen, F. H., Falk, C. T., Motulsky, A. G.
|
|
<strong>Linkage studies in a large kindred with familial hypercholesterolemia.</strong>
|
|
Am. J. Hum. Genet. 26: 598-603, 1974.
|
|
|
|
|
|
[PubMed: 4213615]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pratt, J. R., Basheer, S. A., Sacks, S. H.
|
|
<strong>Local synthesis of complement component C3 regulates acute renal transplant rejection.</strong>
|
|
Nature Med. 8: 582-587, 2002.
|
|
|
|
|
|
[PubMed: 12042808]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm0602-582]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rahpeymai, Y., Hietala, M. A., Wilhelmsson, U., Fotheringham, A., Davies, I., Nilsson, A.-K., Zwirner, J., Wetsel, R. A., Gerard, C., Pekny, M., Pekna, M.
|
|
<strong>Complement: a novel factor in basal and ischemia-induced neurogenesis.</strong>
|
|
EMBO J. 25: 1364-1374, 2006.
|
|
|
|
|
|
[PubMed: 16498410]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.emboj.7601004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Raum, D., Balner, H., Petersen, B. H., Alper, C. A.
|
|
<strong>Genetic polymorphism of serum complement components in the chimpanzee.</strong>
|
|
Immunogenetics 10: 455-468, 1980.
|
|
|
|
|
|
[PubMed: 22457919]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01572581]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Raum, D., Donaldson, V. H., Rosen, F. S., Alper, C. A.
|
|
<strong>Genetics of complement.</strong>
|
|
Curr. Top. Hemat. 3: 111-174, 1980.
|
|
|
|
|
|
[PubMed: 7035077]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reis, E. S., Falcao, D. A., Isaac, L.
|
|
<strong>Clinical aspects and molecular basis of primary deficiencies of complement component C3 and its regulatory proteins factor I and factor H.</strong>
|
|
Scand. J. Immun. 63: 155-168, 2006.
|
|
|
|
|
|
[PubMed: 16499568]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-3083.2006.01729.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roychoudhury, A. K., Nei, M.
|
|
<strong>Human Polymorphic Genes: World Distribution.</strong>
|
|
New York: Oxford Univ. Press (pub.) 1988.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sanders, M. F., Crandall, J., Huey, B., Leung, R., King, M. C.
|
|
<strong>Possible synteny of LE, SE, and C3. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 575 only, 1984.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schonthaler, H. B., Guinea-Viniegra, J., Wculek, S. K., Ruppen, I., Ximenez-Embun, P., Guio-Carrion, A., Navarro, R., Hogg, N., Ashman, K., Wagner, E. F.
|
|
<strong>S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3.</strong>
|
|
Immunity 39: 1171-1181, 2013.
|
|
|
|
|
|
[PubMed: 24332034]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.immuni.2013.11.011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seddon, J. M., Yu, Y., Miller, E. C., Reynolds, R., Tan, P. L., Gowrisankar, S., Goldstein, J. I., Triebwasser, M., Anderson, H. E., Zerbib, J., Kavanagh, D., Souied, E., Katsanis, N., Daly, M. J., Atkinson, J. P., Raychaudhuri, S.
|
|
<strong>Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.</strong>
|
|
Nature Genet. 45: 1366-1370, 2013.
|
|
|
|
|
|
[PubMed: 24036952]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.2741]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sivaprasad, S., Adewoyin, T., Bailey, T. A., Dandekar, S. S., Jenkins, S., Webster, A. R., Chong, N. V.
|
|
<strong>Estimation of systemic complement C3 activity in age-related macular degeneration.</strong>
|
|
Arch. Ophthal. 125: 515-519, 2007.
|
|
|
|
|
|
[PubMed: 17420372]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.125.4.515]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Skok, J., Solomon, E., Reid, K. B. M., Thompson, R. A.
|
|
<strong>Distinct genes for fibroblast and serum C1q.</strong>
|
|
Nature 292: 549-551, 1981.
|
|
|
|
|
|
[PubMed: 6973093]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/292549a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Teisberg, P.
|
|
<strong>New variants in the C3 system.</strong>
|
|
Hum. Hered. 20: 631-637, 1970.
|
|
|
|
|
|
[PubMed: 5514302]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000152369]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Teisberg, P.
|
|
<strong>Another variant in the C3 system.</strong>
|
|
Clin. Genet. 2: 298-302, 1971.
|
|
|
|
|
|
[PubMed: 4112057]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1971.tb00290.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsukamoto, H., Horiuchi, T., Kokuba, H., Nagae, S., Nishizaka, H., Sawabe, T., Harashima, S., Himeji, D., Koyama, T., Otsuka, J., Mitoma. H., Kimoto, Y., Hashimura, C., Kitano, E., Kitamura, H., Furue, M., Harada, M.
|
|
<strong>Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus.</strong>
|
|
Biochem. Biophys. Res. Commun. 330: 298-304, 2005.
|
|
|
|
|
|
[PubMed: 15781264]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2005.02.159]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vasek, M. J., Garber, C., Dorsey, D., Durrant, D. M., Bollman, B., Soung, A., Yu, J., Perez-Torres, C., Frouin, A., Wilton, D. K., Funk, K., DeMasters, B. K., and 10 others.
|
|
<strong>A complement-microglial axis drives synapse loss during virus-induced memory impairment.</strong>
|
|
Nature 534: 538-543, 2016.
|
|
|
|
|
|
[PubMed: 27337340]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature18283]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Walport, M. J.
|
|
<strong>Complement (first of two parts).</strong>
|
|
New Eng. J. Med. 344: 1058-1066, 2001.
|
|
|
|
|
|
[PubMed: 11287977]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM200104053441406]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weitkamp, L. R., Johnston, E., Guttormsen, S. A.
|
|
<strong>Probable genetic linkage between the loci for the Lewis blood group and complement C3.</strong>
|
|
Cytogenet. Cell Genet. 13: 183-184, 1974.
|
|
|
|
|
|
[PubMed: 4827488]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000130268]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wetsel, R. A., Kildsgaard, J., Zsigmond E., Liao, W., Chan, L.
|
|
<strong>Genetic deficiency of acylation stimulating protein (ASP(C3ades-Arg)) does not cause hyperapobetalipoproteinemia in mice.</strong>
|
|
J. Biol. Chem. 274: 19429-19433, 1999.
|
|
|
|
|
|
[PubMed: 10383458]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.274.27.19429]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Whitehead, A. S., Sim, R. B., Bodmer, W. F.
|
|
<strong>A monoclonal antibody against human complement component C3: the production of C3 by human cells in vitro.</strong>
|
|
Europ. J. Immun. 11: 140-146, 1981.
|
|
|
|
|
|
[PubMed: 6163641]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/eji.1830110215]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Whitehead, A. S., Solomon, E., Chambers, S., Bodmer, W. F., Povey, S., Fey, G.
|
|
<strong>Assignment of the structural gene for the third component of human complement to chromosome 19.</strong>
|
|
Proc. Nat. Acad. Sci. 79: 5021-5025, 1982.
|
|
|
|
|
|
[PubMed: 6956911]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.79.16.5021]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wieme, R. J., Demeulenaere, L.
|
|
<strong>Genetically determined electrophoretic variant of the human complement component C-prime-3.</strong>
|
|
Nature 214: 1042-1043, 1967.
|
|
|
|
|
|
[PubMed: 6059034]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/2141042a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wiesmann, C., Katschke, K. J., Jr., Yin, J., Helmy, K. Y., Steffek, M., Fairbrother, W. J., McCallum, S. A., Embuscado, L., DeForge, L., Hass, P. E., van Lookeren Campagne, M.
|
|
<strong>Structure of C3b in complex with CRIg gives insights into regulation of complement activation.</strong>
|
|
Nature 444: 217-220, 2006.
|
|
|
|
|
|
[PubMed: 17051150]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature05263]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Williamson, R.
|
|
<strong>Personal Communication.</strong>
|
|
London, England 8/25/1983.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Winkelstein, J. A., Cork, L. C., Griffin, D. E., Griffin, J. W., Adams, R. J., Price, D. L.
|
|
<strong>Genetically determined deficiency of the third component of complement in the dog.</strong>
|
|
Science 212: 1169-1170, 1981.
|
|
|
|
|
|
[PubMed: 7233211]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.7233211]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Xia, Z., Sniderman, A. D., Cianflone, K.
|
|
<strong>Acylation-stimulating protein (ASP) deficiency induces obesity resistance and increased energy expenditure in ob/ob mice.</strong>
|
|
J. Biol. Chem. 277: 45874-45879, 2002.
|
|
|
|
|
|
[PubMed: 12244109]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M207281200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yates, J. R. W., Sepp, T., Matharu, B. K., Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Hayward, C., Morgan, J., Wright, A. F., Armbrecht, A. M., Dhillon, B., Deary, I. J., Redmond, E., Bird, A. C., Moore, A. T.
|
|
<strong>Complement C3 variant and the risk of age-related macular degeneration.</strong>
|
|
New Eng. J. Med. 357: 553-561, 2007.
|
|
|
|
|
|
[PubMed: 17634448]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa072618]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhan, X., Larson, D. E., Wang, C., Koboldt, D. C., Sergeev, Y. V., Fulton, R. S., Fulton, L. L., Fronick, C. C., Branham, K. E., Bragg-Gresham, J., Jun, G., Hu, Y, and 48 others.
|
|
<strong>Identification of a rare coding variant in complement 3 associated with age-related macular degeneration.</strong>
|
|
Nature Genet. 45: 1375-1379, 2013.
|
|
|
|
|
|
[PubMed: 24036949]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.2758]
|
|
|
|
|
|
</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 : 09/15/2016<br>Paul J. Converse - updated : 08/10/2016<br>Paul J. Converse - updated : 11/6/2014<br>Paul J. Converse - updated : 10/7/2014<br>Ada Hamosh - updated : 1/8/2014<br>Ada Hamosh - updated : 10/22/2013<br>Ada Hamosh - updated : 1/28/2011<br>Paul J. Converse - updated : 6/11/2010<br>Paul J. Converse - updated : 5/25/2010<br>Marla J. F. O'Neill - updated : 1/27/2010<br>Jane Kelly - updated : 10/30/2007<br>Victor A. McKusick - updated : 10/18/2007<br>Marla J. F. O'Neill - updated : 8/21/2007<br>Ada Hamosh - updated : 11/28/2006<br>Paul J. Converse - updated : 7/20/2006<br>Victor A. McKusick - updated : 6/22/2006<br>Ada Hamosh - updated : 11/3/2005<br>Patricia A. Hartz - updated : 4/28/2003<br>Paul J. Converse - updated : 5/31/2002<br>Paul J. Converse - updated : 12/11/2001<br>Victor A. McKusick - updated : 4/25/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/4/1986
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
mgross : 08/12/2020<br>alopez : 09/15/2016<br>mgross : 08/10/2016<br>alopez : 08/03/2016<br>carol : 09/08/2015<br>mgross : 11/7/2014<br>mcolton : 11/6/2014<br>mgross : 10/7/2014<br>alopez : 1/8/2014<br>alopez : 10/22/2013<br>alopez : 8/7/2013<br>carol : 7/6/2012<br>carol : 11/28/2011<br>terry : 5/17/2011<br>carol : 4/25/2011<br>terry : 3/22/2011<br>terry : 3/10/2011<br>carol : 3/1/2011<br>alopez : 2/3/2011<br>alopez : 2/3/2011<br>terry : 1/28/2011<br>mgross : 6/14/2010<br>terry : 6/11/2010<br>wwang : 5/25/2010<br>wwang : 5/25/2010<br>wwang : 1/29/2010<br>terry : 1/27/2010<br>carol : 7/30/2009<br>ckniffin : 7/27/2009<br>terry : 1/13/2009<br>terry : 1/12/2009<br>wwang : 12/27/2007<br>carol : 10/30/2007<br>alopez : 10/23/2007<br>terry : 10/18/2007<br>alopez : 10/4/2007<br>wwang : 8/27/2007<br>terry : 8/21/2007<br>ckniffin : 5/1/2007<br>alopez : 12/7/2006<br>terry : 11/28/2006<br>mgross : 8/7/2006<br>terry : 7/20/2006<br>terry : 6/22/2006<br>alopez : 11/7/2005<br>alopez : 11/7/2005<br>terry : 11/3/2005<br>terry : 5/17/2005<br>carol : 3/17/2004<br>mgross : 2/4/2004<br>terry : 4/28/2003<br>alopez : 5/31/2002<br>alopez : 5/31/2002<br>mgross : 1/9/2002<br>terry : 12/11/2001<br>carol : 4/30/2001<br>mcapotos : 4/26/2001<br>terry : 4/25/2001<br>carol : 8/4/1998<br>dkim : 6/30/1998<br>terry : 11/10/1997<br>mark : 7/30/1995<br>davew : 7/5/1994<br>mimadm : 6/25/1994<br>warfield : 4/8/1994<br>carol : 10/28/1992<br>carol : 8/17/1992
|
|
</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>
|
|
|
|
|