4918 lines
431 KiB
Text
4918 lines
431 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
|
|
|
|
- *516030 - COMPLEX IV, CYTOCHROME c OXIDASE SUBUNIT I; MTCO1
|
|
|
|
|
|
- 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=516030"><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">*516030</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="#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="#mapping">Mapping</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="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/516030">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=ENSG00000198804;t=-" 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://mitomap.org/bin/view.pl/Main/SearchSite?search=MT-CO1" class="mim-tip-hint" title="A curated repository of published and unpublished data on human mitochondrial DNA variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MITOMAP', 'domain': 'mitomap.org'})">MITOMAP</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=4512" 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=516030" 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=ENSG00000198804;t=-" 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</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=516030" 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://www.proteinatlas.org/search/MT-CO1" 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/116977,506829,251831109" 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/P00395" 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=4512" 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=ENSG00000198804;t=-" 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=MT-CO1" 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=MT-CO1" 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+4512" 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/MT-CO1" 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:4512" 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/4512" 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>
|
|
</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:7419" 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=516030[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=516030[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/MT-CO1/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/ENSG00000198804" 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.gwascentral.org/search?q=MT-CO1" 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=MT-CO1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=MT-CO1&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/PA31225" 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:7419" 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/FBgn0013674.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:102504" 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/MT-CO1#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:102504" 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/4512/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=4512" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4512" 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=MT-CO1&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> 58610003, 67434000<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> H47.22<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>
|
|
516030
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
COMPLEX IV, CYTOCHROME c OXIDASE SUBUNIT I; MTCO1
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
CYTOCHROME c OXIDASE I; CO1; COX1
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MT-CO1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MT-CO1</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</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>Cytochrome c oxidase subunit I (CO1 or MTCO1) is 1 of 3 mitochondrial DNA (mtDNA) encoded subunits (MTCO1, MTCO2, MTCO3) of respiratory Complex IV. Complex IV is located within the mitochondrial inner membrane and is the third and final enzyme of the electron transport chain of mitochondrial oxidative phosphorylation. It collects electrons from reduced cytochrome c and transfers them to oxygen to give water. The energy released is used to transport protons across the mitochondrial inner membrane. Complex IV is composed of 13 polypeptides. Subunits I, II, and III (MTCO1, MTCO2, MTCO3) are encoded by mtDNA while subunits IV, Va, Vb, VIa, VIb, VIc, VIIa, VIIb, VIIc, and VIII are nuclear encoded (<a href="#24" class="mim-tip-reference" title="Kadenbach, B., Jarausch, J., Hartmann, R., Merle, P. <strong>Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoretic procedure.</strong> Anal. Biochem. 129: 517-521, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6303162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6303162</a>] [<a href="https://doi.org/10.1016/0003-2697(83)90586-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6303162">Kadenbach et al., 1983</a>; <a href="#39" class="mim-tip-reference" title="Shoffner, J. M., Wallace, D. C. <strong>Oxidative phosphorylation diseases.In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic and Molecular Bases of Inherited Disease. Vol. 1. (7th ed.)</strong> New York: McGraw-Hill (pub.) 1995. Pp. 1535-1609."None>Shoffner and Wallace, 1995</a>). While the mammalian Complex IV has a complex structure, several prokaryotic enzyme systems have the same catalytic functions, but are much simpler. These systems have been amenable to cloning and in vitro mutagenesis permitting detailed structure-function studies. Two well-studied systems are the cytochrome aa3 (cytochrome c oxidase) of Rhodobacter sphaeroides and the cytochrome bo (ubiquinol oxidase) of Escherichia coli. The R. sphaeroides enzyme has 3 subunits that are homologous to the 3 mammalian mtDNA subunits. R. sphaeroides subunit I is 62.1 kD and 52% identical and 76% similar to beef heart MTCO1; subunit II is 32.9 kD and 39% identical and 63% similar to beef MTCO2, and subunit III is 30.1 kD and 49% identical and 71% similar to beef heart. The Soret maxred = 444.5 nm (bovine = 443 nm) and alpha-band maxred = 606 nm (bovine = 604 nm). The extinction coefficients are identical (<a href="#21" class="mim-tip-reference" title="Hosler, J. P., Ferguson-Miller, S., Calhoun, M. W., Thomas, J. W., Hill, J., Lemieux, L., Ma, J., Georgiou, C., Fetter, J., Shapleigh, J., Tecklenburg, M. M. J., Babcock, G. T., Gennis, R. B. <strong>Insight into the active-site structure and function of cytochrome oxidase by analysis of site-directed mutants of bacterial cytochrome aa3 and cytochrome bo.</strong> J. Bioenerg. Biomembr. 25: 121-136, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8389745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8389745</a>] [<a href="https://doi.org/10.1007/BF00762854" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8389745">Hosler et al., 1993</a>). These and other studies (<a href="#8" class="mim-tip-reference" title="Capaldi, R. A. <strong>Structure and function of cytochrome c oxidase.</strong> Annu. Rev. Biochem. 59: 569-596, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2165384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2165384</a>] [<a href="https://doi.org/10.1146/annurev.bi.59.070190.003033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2165384">Capaldi, 1990</a>) have generated the following functional outlines for this enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2165384+6303162+8389745" 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 cytochrome c oxidase family of enzymes have 4 redox centers, 2 hemes and 2 copper centers. In mitochondrial Complex IV, the 2 hemes are a and a3 and the 2 coppers are CuA and CuB. The 2 hemes and CuB are bound to subunit I. For R. sphaeroides subunit I and for mammalian MTCO1, there are 12 membrane-spanning alpha-helices (I to XII). Of these helices, heme a is located between helix II and X, ligated with the invariant histidines at amino acid 102 (MTCO1 88) of helix II and at 421 (MTCO1 378) of helix X. Helix X lies between heme a and heme a3, with heme a3 bound to the opposite side of helix X at invariant histidine at amino acid 419 (MTCO1 376). Heme a3 is a component of a binuclear center which includes CuB and where oxygen is reduced to water. CuB is thought to lie adjacent to the iron of heme a3 and to be ligated to helix VI through invariant histidine 284 (MTCO1 240) and to helix VII through invariant histidines 333 and 334 (MTCO1 290 and 291). Amino acids histidine 411 (MTCO1 368), aspartate 412 (369), threonine 413 (370), and tyrosine 414 (371) occur in the conserved loop between helices IX and X, lying close to hemes a and a3, and may be in the proximity of the CuA located in subunit II (<a href="#21" class="mim-tip-reference" title="Hosler, J. P., Ferguson-Miller, S., Calhoun, M. W., Thomas, J. W., Hill, J., Lemieux, L., Ma, J., Georgiou, C., Fetter, J., Shapleigh, J., Tecklenburg, M. M. J., Babcock, G. T., Gennis, R. B. <strong>Insight into the active-site structure and function of cytochrome oxidase by analysis of site-directed mutants of bacterial cytochrome aa3 and cytochrome bo.</strong> J. Bioenerg. Biomembr. 25: 121-136, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8389745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8389745</a>] [<a href="https://doi.org/10.1007/BF00762854" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8389745">Hosler et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8389745" 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>Subunit II of Complex IV interacts with cytochrome c and contains the CuA center. This means that the pathway of electron transfer through Complex IV is from cytochrome c, to CuA, to cytochrome a, and then to the binuclear center of cytochrome a3-CuB. It is thought that the transfer of electrons from cytochrome a to the binuclear center is the key control point in the reaction and one of the major points of energy transduction (<a href="#19" class="mim-tip-reference" title="Hill, B. C. <strong>The sequence of electron carriers in the reaction of cytochrome c oxidase with oxygen.</strong> J. Bioenerg. Biomembr. 25: 115-120, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8389744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8389744</a>] [<a href="https://doi.org/10.1007/BF00762853" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8389744">Hill, 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8389744" 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>Proton translocation in Complex IV involves four electrons to reduce O2 and four protons taken up from the matrix side of the mitochondrial membrane for the formation of H2O. Four more protons are vertically translocated from the matrix to the cytosol side of the membrane. Evidence is accumulating that proton translocation is linked to electron transfer at the binuclear oxygen (O2) binding site, which has been extended to suggest that proton translocation is associated with proximal ligand exchange between tyrosine and histidine on cytochrome a3 (<a href="#38" class="mim-tip-reference" title="Rousseau, D. L., Ching, Y., Wang, J. <strong>Proton translocation in cytochrome c oxidase: redox linkage through proximal ligand exchange on cytochrome a3.</strong> J. Bioenerg. Biomembr. 25: 165-176, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8389749/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8389749</a>] [<a href="https://doi.org/10.1007/BF00762858" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8389749">Rousseau et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8389749" 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 toxicity of classical inhibitors of Complex IV is the result of drug interaction with these reactive sites. Cyanide and azide form a bridge between cytochrome a3 and CuB. Thiocyanate and formate bind elsewhere on the binuclear center, probably at CuB (<a href="#33" class="mim-tip-reference" title="Palmer, G. <strong>Current issues in the chemistry of cytochrome c oxidase.</strong> J. Bioenerg. Biomembr. 25: 145-151, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8389747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8389747</a>] [<a href="https://doi.org/10.1007/BF00762856" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8389747">Palmer, 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8389747" 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>Subunit III is an universal component of cytochrome c oxidase. Previously, it was thought to participate in proton translocation because dicyclohexylcarbodiimide (DCCD), a inhibitor of proton transport in other systems, binds to the glutamate at position 90 in subunit III (<a href="#37" class="mim-tip-reference" title="Prochaska, L. J., Bisson, R., Capaldi, R. A., Steffens, G. C., Buse, G. <strong>Inhibition of cytochrome c oxidase function by dicyclohexylcarbodiimide.</strong> Biochim. Biophys. Acta 637: 360-373, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6271198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6271198</a>] [<a href="https://doi.org/10.1016/0005-2728(81)90175-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6271198">Prochaska et al., 1981</a>). However, more recent studies place this function at the binuclear center in subunit I. Hence, the function of subunit III remains unclear. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6271198" 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 functions of the 10 nuclear encoded Complex IV subunits is just beginning to be elucidated. Three of the subunits, VIa, VIIa, and VIII, have two isoforms, one expressed in heart and skeletal muscle and the other in the remaining tissues (<a href="#8" class="mim-tip-reference" title="Capaldi, R. A. <strong>Structure and function of cytochrome c oxidase.</strong> Annu. Rev. Biochem. 59: 569-596, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2165384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2165384</a>] [<a href="https://doi.org/10.1146/annurev.bi.59.070190.003033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2165384">Capaldi, 1990</a>; <a href="#26" class="mim-tip-reference" title="Lomax, M. I., Grossman, L. I. <strong>Tissue-specific genes for respiratory proteins.</strong> Trends Biochem. Sci. 14: 501-503, 1989. Note: Erratum: Trends Biochem. Sci. 15: 217 only, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2560276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2560276</a>] [<a href="https://doi.org/10.1016/0968-0004(89)90185-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2560276">Lomax and Grossman, 1989</a>). The differential expression of this genes is in part the product of differential transcription (<a href="#45" class="mim-tip-reference" title="Wallace, D. C. <strong>Mitochondrial diseases: genotype versus phenotype.</strong> Trends Genet. 9: 128-133, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8516847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8516847</a>] [<a href="https://doi.org/10.1016/0168-9525(93)90207-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8516847">Wallace, 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2560276+2165384+8516847" 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>MTCO1 is encoded by the guanine-rich heavy (H) strand of the mtDNA and located between nucleotide pairs (nps) 5904 and 7444 (<a href="#2" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#42" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). It is maternally inherited along with the mtDNA (<a href="#14" class="mim-tip-reference" title="Giles, R. E., Blanc, H., Cann, H. M., Wallace, D. C. <strong>Maternal inheritance of human mitochondrial DNA.</strong> Proc. Nat. Acad. Sci. 77: 6715-6719, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6256757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6256757</a>] [<a href="https://doi.org/10.1073/pnas.77.11.6715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6256757">Giles et al., 1980</a>; <a href="#9" class="mim-tip-reference" title="Case, J. T., Wallace, D. C. <strong>Maternal inheritance of mitochondrial DNA polymorphisms in cultured human fibroblasts.</strong> Somat. Cell Genet. 7: 103-108, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261411</a>] [<a href="https://doi.org/10.1007/BF01544751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6261411">Case and Wallace, 1981</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6256757+7219534+6261411" 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>The MTCO1 gene encompasses 1540 nps of continuous mtDNA which lacks introns and encodes a single polypeptide. The mRNA begins with a 12-np 5-prime nontranslated sequence, then the AUG start codon, the polypeptide coding sequence which ends in an AGA codon which serves as a stop codon, and the extends 72 nps through the antisense tRNAser(UCN) that serves as a 3-prime nontranslated region (<a href="#30" class="mim-tip-reference" title="Ojala, D., Montoya, J., Attardi, G. <strong>tRNA punctuation model of RNA processing in human mitochondria.</strong> Nature 290: 470-474, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219536</a>] [<a href="https://doi.org/10.1038/290470a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219536">Ojala et al., 1981</a>; <a href="#3" class="mim-tip-reference" title="Attardi, G., Chomyn, A., Montoya, J., Ojala, D. <strong>Identification and mapping of human mitochondrial genes.</strong> Cytogenet. Cell Genet. 32: 85-98, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7140372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7140372</a>] [<a href="https://doi.org/10.1159/000131689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7140372">Attardi et al., 1982</a>). The MTCO1 gene is transcribed as a part of the polycistronic H-strand transcript flanked by tRNAtyr at the 5-prime end and tRNAasp at the 3-prime end. Then these tRNAs are cleaved out of the transcript freeing transcript 9, the mRNA for MTCO1. The mRNA is then polyadenylated (<a href="#2" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#30" class="mim-tip-reference" title="Ojala, D., Montoya, J., Attardi, G. <strong>tRNA punctuation model of RNA processing in human mitochondria.</strong> Nature 290: 470-474, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219536</a>] [<a href="https://doi.org/10.1038/290470a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219536">Ojala et al., 1981</a>; <a href="#3" class="mim-tip-reference" title="Attardi, G., Chomyn, A., Montoya, J., Ojala, D. <strong>Identification and mapping of human mitochondrial genes.</strong> Cytogenet. Cell Genet. 32: 85-98, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7140372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7140372</a>] [<a href="https://doi.org/10.1159/000131689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7140372">Attardi et al., 1982</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7140372+7219536+7219534" 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>The predicted molecular weight (MW) of MTCO1 is 57 kD (<a href="#2" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#42" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). However, its apparent MW on SDS-polyacrylamide gels (PAGE) is somewhat less. Using Tris-glycine buffer it runs at 39.5 kD (<a href="#31" class="mim-tip-reference" title="Oliver, N. A., McCarthy, J., Wallace, D. C. <strong>Comparison of mitochondrially synthesized polypeptides of human, mouse, and monkey cell lines by a two-dimensional protease gel system.</strong> Somat. Cell Molec. Genet. 10: 639-643, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438810</a>] [<a href="https://doi.org/10.1007/BF01535230" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438810">Oliver et al., 1984</a>; <a href="#32" class="mim-tip-reference" title="Oliver, N. A., Wallace, D. C. <strong>Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction.</strong> Molec. Cell. Biol. 2: 30-41, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6955589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6955589</a>] [<a href="https://doi.org/10.1128/mcb.2.1.30-41.1982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6955589">Oliver and Wallace, 1982</a>; <a href="#44" class="mim-tip-reference" title="Wallace, D. C., Yang, J., Ye, J., Lott, M. T., Oliver, N. A., McCarthy, J. <strong>Computer prediction of peptide maps: assignment of polypeptides to human and mouse mitochondrial DNA genes by analysis of two dimensional-proteolytic digest gels.</strong> Am. J. Hum. Genet. 38: 461-481, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3518425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3518425</a>]" pmid="3518425">Wallace et al., 1986</a>), whereas using urea-phosphate gives an apparent MW of 45 kD (<a href="#10" class="mim-tip-reference" title="Ching, E., Attardi, G. <strong>High-resolution electrophoretic fractionation and partial characterization of the mitochondrial translation products from HeLa cells.</strong> Biochemistry 21: 3188-3195, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6285960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6285960</a>] [<a href="https://doi.org/10.1021/bi00256a024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6285960">Ching and Attardi, 1982</a>; <a href="#17" class="mim-tip-reference" title="Hare, J. F., Ching, E., Attardi, G. <strong>Isolation, subunit composition and site of synthesis of human cytochrome c oxidase.</strong> Biochemistry 19: 2023-2030, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6246917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6246917</a>] [<a href="https://doi.org/10.1021/bi00551a003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6246917">Hare et al., 1980</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6955589+6246917+7219534+3518425+6285960+6438810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Acin-Perez, R., Bayona-Bafaluy, M. P., Bueno, M., Machicado, C., Fernandez-Silva, P., Perez-Martos, A., Montoya, J., Lopez-Perez, M. J., Sancho, J., Enriquez, J. A. <strong>An intragenic suppressor in the cytochrome c oxidase I gene of mouse mitochondrial DNA.</strong> Hum. Molec. Genet. 12: 329-339, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12554686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12554686</a>] [<a href="https://doi.org/10.1093/hmg/ddg021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12554686">Acin-Perez et al. (2003)</a> identified a cell line containing single and double missense mutations in the cytochrome c oxidase (COX) subunit I gene of mouse mitochondrial DNA. When present in homoplasmy, the single mutant displayed a normal complex IV assembly but a significantly reduced COX activity, while the double mutant almost completely compensated the functional defect of the first mutation. The authors hypothesized that deleterious mutations can arise and become predominant; cultured cells can maintain several mtDNA haplotypes at stable frequencies; the respiratory chain has little spare COX capacity; and that the size of a cavity in the vicinity of val421 in MTCO1I of animal COX may affect the function of the enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12554686" 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="Wisloff, U., Najjar, S. M., Ellingsen, O., Haram, P. M., Swoap, S., Al-Share, Q., Fernstrom, M., Rezaei, K., Lee, S. J., Koch, L. G., Britton, S. L. <strong>Cardiovascular risk factors emerge after artificial selection for low aerobic capacity.</strong> Science 307: 418-420, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15662013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15662013</a>] [<a href="https://doi.org/10.1126/science.1108177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15662013">Wisloff et al. (2005)</a> hypothesized that artificial selection of rats based on low and high intrinsic exercise capacity would yield models that also contrast for cardiovascular disease risk. After 11 generations, rats with low aerobic capacity scored higher on cardiovascular risk factors that constitute the metabolic syndrome. The decrease in aerobic capacity was associated with decreases in the amounts of transcription factors required for mitochondrial biogenesis and in the amounts of oxidative enzymes in skeletal muscle. <a href="#47" class="mim-tip-reference" title="Wisloff, U., Najjar, S. M., Ellingsen, O., Haram, P. M., Swoap, S., Al-Share, Q., Fernstrom, M., Rezaei, K., Lee, S. J., Koch, L. G., Britton, S. L. <strong>Cardiovascular risk factors emerge after artificial selection for low aerobic capacity.</strong> Science 307: 418-420, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15662013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15662013</a>] [<a href="https://doi.org/10.1126/science.1108177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15662013">Wisloff et al. (2005)</a> found that the amount of PPARG (<a href="/entry/601487">601487</a>), PPARG coactivator-1-alpha (PPARGC1A; <a href="/entry/604517">604517</a>), ubiquinol-cytochrome c oxidoreductase core 2 subunit (UQCRC2; <a href="/entry/191329">191329</a>), cytochrome c oxidase subunit I (MTCO1), uncoupling protein-2 (UCP2; <a href="/entry/601693">601693</a>), and ATP synthase H(+)-transporting mitochondrial F1 complex (F1-ATP synthase; see <a href="/entry/108729">108729</a>) were markedly reduced in the low capacity runner rats in comparison with the high capacity runners. The uniform decline in these proteins was consistent with the hypothesis that reduced aerobic metabolism plays a causal role in the development of the differences between the low capacity runner and high capacity runner rats. <a href="#47" class="mim-tip-reference" title="Wisloff, U., Najjar, S. M., Ellingsen, O., Haram, P. M., Swoap, S., Al-Share, Q., Fernstrom, M., Rezaei, K., Lee, S. J., Koch, L. G., Britton, S. L. <strong>Cardiovascular risk factors emerge after artificial selection for low aerobic capacity.</strong> Science 307: 418-420, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15662013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15662013</a>] [<a href="https://doi.org/10.1126/science.1108177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15662013">Wisloff et al. (2005)</a> concluded that impairment of mitochondrial function may link reduced fitness to cardiovascular and metabolic disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15662013" 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="#40" class="mim-tip-reference" title="Temperley, R., Richter, R. Dennerlein, S., Lightowlers, R. N., Chrzanowska-Lightowlers, Z. M. <strong>Hungry codons promote frameshifting in human mitochondrial ribosomes.</strong> Science 327: 301 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20075246/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20075246</a>] [<a href="https://doi.org/10.1126/science.1180674" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20075246">Temperley et al. (2010)</a> demonstrated that human mitoribosomes do invoke -1 frameshift at the AGA and AGG codons predicted to terminate the 2 ORFs in MTCO1 and MTND6 (<a href="/entry/516006">516006</a>), respectively. As a consequence, both ORFs terminate in the standard UAG codon, necessitating the use of only a single mitochondrial release factor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20075246" 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 immunoblot analysis, <a href="#18" class="mim-tip-reference" title="Hayashi, T., Asano, Y., Shintani, Y., Aoyama, H., Kioka, H., Tsukamoto, O., Hikita, M., Shinzawa-Itoh, K., Takafuji, K., Higo, S., Kato, H., Yamazaki, S., and 13 others. <strong>Higd1a is a positive regulator of cytochrome c oxidase.</strong> Proc. Nat. Acad. Sci. 112: 1553-1558, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25605899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25605899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25605899[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/10.1073/pnas.1419767112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25605899">Hayashi et al. (2015)</a> showed that Higd1a (<a href="/entry/618623">618623</a>) expression was induced early in rat cardiomyocytes exposed to hypoxia. Immunoprecipitation analysis revealed that Higd1a directly associated with cytochrome c oxidase (CcO) and integrated into the CcO macromolecular complex, causing structural changes at heme a, the active center of CcO. Knockdown and overexpression analyses demonstrated that Higd1a positively regulated CcO activity and increased mitochondrial ATP production, thereby protecting cardiomyocytes against hypoxia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25605899" 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>Restriction site polymorphisms have been identified at the following nucleotide positions for the indicated enzymes (where '+' = site gain, '-' = site loss relative to the reference sequence, <a href="#2" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>): Alu I: -5978, -5996, -6022, -6204, -6867, +7025, -7055; Ava II: +5984, +6332, +6581, +6699 (or 8719 or 8723); Dde I: -6296, +6356, -6377, -7103; Hae III: -6027, -6260, +6425, +6534, +6618, -6957, +7325, +7347; Hha I: -5971, +6166 or 6168; HinfI: -5983, -6211, +6610, -6871, -6931; Mbo I: -6904; Msp I: +6501, -6688, +7159; Pst I:-6910; Rsa I: +5985, +6915, -7013, +7241; Taq I: +6049 or 7854, -7335; Xba I: -7440 (<a href="#42" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219534" 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>One phenotypically relevant mutation localized to MTCO1 contributes to the etiology of Leber hereditary optic neuropathy (LHON; <a href="/entry/535000">535000</a>) and is designated MTCO1*LHON7444A (<a href="#0001">516030.0001</a>).</p><p><a href="#11" class="mim-tip-reference" title="Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., Parker, W. D., Jr. <strong>Mutations in mitochondrial cytosome c oxidase genes segregate with late-onset Alzheimer disease.</strong> Proc. Nat. Acad. Sci. 94: 4526-4531, 1997. Note: Retraction: Proc. Nat.Acad. Sci. 95: 12069 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9114023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9114023</a>] [<a href="https://doi.org/10.1073/pnas.94.9.4526" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9114023">Davis et al. (1997)</a> reported that 2 mitochondrial genes, the MTCO1 gene and the MTCO2 gene (<a href="/entry/516040">516040</a>), encoding CO subunits I and II, respectively, appeared to be associated with late-onset Alzheimer disease (see <a href="/entry/502500">502500</a>); however, their work was later retracted. Prior to the retraction, <a href="#20" class="mim-tip-reference" title="Hirano, M., Shtilbans, A., Mayeux, R., Davidson, M. M., DiMauro, S., Knowles, J. A., Schon, E. A. <strong>Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes.</strong> Proc. Nat. Acad. Sci. 94: 14894-14899, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9405710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9405710</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9405710[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/10.1073/pnas.94.26.14894" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9405710">Hirano et al. (1997)</a> had noted that the DNA isolation method used by <a href="#11" class="mim-tip-reference" title="Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., Parker, W. D., Jr. <strong>Mutations in mitochondrial cytosome c oxidase genes segregate with late-onset Alzheimer disease.</strong> Proc. Nat. Acad. Sci. 94: 4526-4531, 1997. Note: Retraction: Proc. Nat.Acad. Sci. 95: 12069 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9114023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9114023</a>] [<a href="https://doi.org/10.1073/pnas.94.9.4526" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9114023">Davis et al. (1997)</a> resulted in the coamplification of both authentic mtDNA-encoded COX genes and highly similar COX-like sequences embedded in nuclear DNA ('mtDNA pseudogenes'). <a href="#20" class="mim-tip-reference" title="Hirano, M., Shtilbans, A., Mayeux, R., Davidson, M. M., DiMauro, S., Knowles, J. A., Schon, E. A. <strong>Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes.</strong> Proc. Nat. Acad. Sci. 94: 14894-14899, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9405710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9405710</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9405710[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/10.1073/pnas.94.26.14894" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9405710">Hirano et al. (1997)</a> concluded that the observed heteroplasmy was an artifact. <a href="#43" class="mim-tip-reference" title="Wallace, D. C., Stugard, C., Murdock, D., Schurr, T., Brown, M. D. <strong>Ancient mtDNA sequences in the human nuclear genome: a potential source of errors in identifying pathogenic mutations.</strong> Proc. Nat. Acad. Sci. 94: 14900-14905, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9405711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9405711</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9405711[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/10.1073/pnas.94.26.14900" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9405711">Wallace et al. (1997)</a> had come to a similar conclusion. Using the same PCR primers utilized by <a href="#11" class="mim-tip-reference" title="Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., Parker, W. D., Jr. <strong>Mutations in mitochondrial cytosome c oxidase genes segregate with late-onset Alzheimer disease.</strong> Proc. Nat. Acad. Sci. 94: 4526-4531, 1997. Note: Retraction: Proc. Nat.Acad. Sci. 95: 12069 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9114023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9114023</a>] [<a href="https://doi.org/10.1073/pnas.94.9.4526" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9114023">Davis et al. (1997)</a> to amplify CO1 and CO2 sequences from 2 independent mtDNA-less cell lines, they could amplify CO1 and CO2 sequences from both, demonstrating that these sequences are also present in the human nuclear DNA. Furthermore, they found all 5 of the mutations found by <a href="#11" class="mim-tip-reference" title="Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., Parker, W. D., Jr. <strong>Mutations in mitochondrial cytosome c oxidase genes segregate with late-onset Alzheimer disease.</strong> Proc. Nat. Acad. Sci. 94: 4526-4531, 1997. Note: Retraction: Proc. Nat.Acad. Sci. 95: 12069 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9114023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9114023</a>] [<a href="https://doi.org/10.1073/pnas.94.9.4526" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9114023">Davis et al. (1997)</a> in addition to 32 single-base substitutions, including 2 in adjacent tRNAs, and a 2-bp deletion in the CO2 gene. Phylogenetic analysis of the nuclear CO1 and CO2 sequences revealed that they diverges from modern human mtDNAs early in the hominid evolution about 770,000 years before the present. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9114023+9405711+9405710" 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>Deficiency of cytochrome c oxidase (COX) causes a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders in childhood and adulthood and theoretically can result from either nuclear or mitochondrial mutations with obvious differences in mode of inheritance (see <a href="/entry/220110">220110</a>). <a href="#35" class="mim-tip-reference" title="Parfait, B., Percheron, A., Chretien, D., Rustin, P., Munnich, A., Rotig, A. <strong>No mitochondrial cytochrome oxidase (COX) gene mutations in 18 cases of COX deficiency.</strong> Hum. Genet. 101: 247-250, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9402980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9402980</a>] [<a href="https://doi.org/10.1007/s004390050625" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9402980">Parfait et al. (1997)</a> sequenced the 3 mitochondrially encoded COX subunits of complex IV to test for causative mutations in these genes. The study was performed in a series of 18 patients with isolated COX deficiency. They failed to detect any deleterious mutations in this series. Moreover, no mtDNA deletion was observed and sequencing of the flanking tRNA gene involved in the maturation of the COX transcripts failed to detect deleterious mutations as well. Their study supported the view that the disease-causing mutations do not lie in the mitochondrial genome but rather in the nuclear genes encoding either the COX subunits or the proteins involved in assembly of the complex. The results suggested further that a recurrence risk of 25% (as for an autosomal recessive mode of inheritance) can be used in genetic counseling of COX deficiencies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9402980" 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>Most mtDNA mutations that cause human disease are mild to moderately deleterious, yet many random mtDNA changes would be expected to be severe. To determine the fate of the more severe mtDNA mutations, <a href="#12" class="mim-tip-reference" title="Fan, W., Waymire, K. G., Narula, N., Li, P., Rocher, C., Coskun, P. E., Vannan, M. A., Narula, J., MacGregor, G. R., Wallace, D. C. <strong>A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations.</strong> Science 319: 958-962, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18276892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18276892</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18276892[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.1147786" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18276892">Fan et al. (2008)</a> introduced mtDNAs containing 2 mutations that affect oxidative phosphorylation, one mild and one severe, into the female mouse germ line. The severe mutation, 13885insC, created a frameshift mutation in the ND6 gene (<a href="/entry/516006">516006</a>). When homoplasmic, this mutation inactivates oxidative phosphorylation complex I. The mild mutation was a missense mutation, T6589C, in the COI gene that converted the highly conserved valine at codon 421 to alanine (V421A). When homoplasmic, this mutation reduces the activity of oxidative phosphorylation complex IV by 50%. <a href="#12" class="mim-tip-reference" title="Fan, W., Waymire, K. G., Narula, N., Li, P., Rocher, C., Coskun, P. E., Vannan, M. A., Narula, J., MacGregor, G. R., Wallace, D. C. <strong>A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations.</strong> Science 319: 958-962, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18276892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18276892</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18276892[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.1147786" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18276892">Fan et al. (2008)</a> observed that the severe ND6 mutation was selectively eliminated during oogenesis within 4 generations, whereas the milder COI mutation was retained throughout multiple generations even though the offspring consistently developed mitochondrial myopathy and cardiomyopathy. Thus, <a href="#12" class="mim-tip-reference" title="Fan, W., Waymire, K. G., Narula, N., Li, P., Rocher, C., Coskun, P. E., Vannan, M. A., Narula, J., MacGregor, G. R., Wallace, D. C. <strong>A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations.</strong> Science 319: 958-962, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18276892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18276892</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18276892[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.1147786" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18276892">Fan et al. (2008)</a> concluded that severe mitochondrial DNA mutations appear to be selectively eliminated from the female germ line, thereby minimizing their impact on population fitness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18276892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>11 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/516030" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=516030[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 LEBER OPTIC ATROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
DEAFNESS, AMINOGLYCOSIDE-INDUCED, INCLUDED<br />
|
|
DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, LHON7444A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199474822 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199474822;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=rs199474822" 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=rs199474822" 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=RCV000010299 OR RCV000010300 OR RCV000010301 OR RCV000854073 OR RCV001268422 OR RCV003319164" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010299, RCV000010300, RCV000010301, RCV000854073, RCV001268422, RCV003319164" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010299...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See <a href="/entry/535000">535000</a>. This allele converts the AGA termination codon to a lysine codon (AAA), permitting extension of the MTCO1 polypeptide by 3 amino acids (lysine, glutamine, lysine) into the antisense tRNAser(UCN) sequence (<a href="#4" class="mim-tip-reference" title="Brown, M. D., Voljavec, A. S., Lott, M. T., MacDonald, I., Wallace, D. C. <strong>Leber's hereditary optic neuropathy; a model for mitochondrial neurodegenerative diseases.</strong> FASEB J. 6: 2791-2799, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1634041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1634041</a>] [<a href="https://doi.org/10.1096/fasebj.6.10.1634041" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1634041">Brown et al., 1992</a>; <a href="#23" class="mim-tip-reference" title="Johns, D. R., Neufeld, M. J. <strong>Cytochrome c oxidase mutations in Leber hereditary optic neuropathy.</strong> Biochem. Biophys. Res. Commun. 196: 810-815, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8240356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8240356</a>] [<a href="https://doi.org/10.1006/bbrc.1993.2321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8240356">Johns and Neufeld, 1993</a>). The mutation is associated with an impaired mobility of the polypeptide on SDS-PAGE and a 36% reduction in Complex IV activity in patient lymphoblasts. Patients with this mutation cluster within the Caucasian mtDNA phylogenetic tree (<a href="#4" class="mim-tip-reference" title="Brown, M. D., Voljavec, A. S., Lott, M. T., MacDonald, I., Wallace, D. C. <strong>Leber's hereditary optic neuropathy; a model for mitochondrial neurodegenerative diseases.</strong> FASEB J. 6: 2791-2799, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1634041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1634041</a>] [<a href="https://doi.org/10.1096/fasebj.6.10.1634041" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1634041">Brown et al., 1992</a>). However, the 2 cases that have been extensively studied also harbor other LHON mutations: the MTND1*LHON3460A mutation in one case and the MTND6*LHON14484A in the other. Hence, the MTCO1*LHON7444A mutation is probably a secondary LHON mutation (<a href="#5" class="mim-tip-reference" title="Brown, M. D., Wallace, D. C. <strong>Molecular basis of mitochondrial DNA disease.</strong> J. Bioenerg. Biomembr. 26: 263-279, 1994."None>Brown and Wallace, 1994</a>). In the 2 families that harbored this mutation, between 23 and 43% of the maternal relatives were affected with all the affected individuals being male (Brown, Lott and Wallace, unpublished data). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8240356+1634041" 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="#34" class="mim-tip-reference" title="Pandya, A., Xia, X.-J., Erdenetungalag, R., Amendola, M., Landa, B., Radnaabazar, J., Dangaasuren, B., Van Tuyle, G., Nance, W. E. <strong>Heterozygous point mutations in the mitochondrial tRNA Ser(UCN) precursor coexisting with the A1555G mutation in deaf students from Mongolia. (Letter)</strong> Am. J. Hum. Genet. 65: 1803-1806, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577941</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10577941[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302658" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10577941">Pandya et al. (1999)</a> reported 6 unrelated Mongolian deaf students with cosegregation of a 7444G-A mutation and a 1555A-G mutation in the MTRNR1 gene (<a href="/entry/561000#0001">561000.0001</a>). Five of the individuals had a family history consistent with matrilineal transmission of hearing loss (<a href="/entry/500008">500008</a>). Only 2 individuals had a definite history of aminoglycoside exposure, but all 6 had severe to profound bilateral sensorineural hearing loss detected at birth or in infancy. <a href="#34" class="mim-tip-reference" title="Pandya, A., Xia, X.-J., Erdenetungalag, R., Amendola, M., Landa, B., Radnaabazar, J., Dangaasuren, B., Van Tuyle, G., Nance, W. E. <strong>Heterozygous point mutations in the mitochondrial tRNA Ser(UCN) precursor coexisting with the A1555G mutation in deaf students from Mongolia. (Letter)</strong> Am. J. Hum. Genet. 65: 1803-1806, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577941</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10577941[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/302658" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10577941">Pandya et al. (1999)</a> suggested that the 7444G-A mutation would share a common pathogenic mechanism as the adjacent 7445A-G mutation (<a href="/entry/590080#0002">590080.0002</a>) in the MTTS1 gene, which results in aberrant processing of the tRNA-ser(UCN) precursor (see <a href="#16" class="mim-tip-reference" title="Guan, M.-X., Enriquez, J. A., Fischel-Ghodsian, N., Puranam, R. S., Lin, C. P., Maw, M. A., Attardi, G. <strong>The deafness-associated mitochondrial DNA mutation at position 7445, which effects tRNA-ser(UCN) precursor processing, has long-range affects on NADH dehydrogenase subunit ND6 gene expression.</strong> Molec. Cell. Biol. 18: 5868-5879, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9742104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9742104</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9742104[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/10.1128/MCB.18.10.5868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9742104">Guan et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10577941+9742104" 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="Yuan, H., Qian, Y., Xu, Y., Cao, J., Bai, L., Shen, W., Ji, F., Zhang, X., Kang, D., Mo, J. Q., Greinwald, J. H., Han, D., Zhai, S., Young, W.-Y., Guan, M.-X. <strong>Cosegregation of the G7444A mutation in the mitochondrial COI/tRNA-Ser(UCN) genes with the 12S rRNA A1555G mutation in a Chinese family with aminoglycoside-induced and nonsyndromic hearing loss.</strong> Am. J. Med. Genet. 138A: 133-140, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16152638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16152638</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16152638[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/10.1002/ajmg.a.30952" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16152638">Yuan et al. (2005)</a> reported cosegregation of a homoplasmic 7444G-A mutation and a homoplasmic 1555A-G MTRNR1 mutation in a 3-generation Chinese family with aminoglycoside-induced sensorineural hearing loss (<a href="/entry/580000">580000</a>). One additional family member with both mutations, who had a history of exposure to noise but not to aminoglycoside, exhibited mild hearing impairment. The dosage and age at the time of drug administration seemed to be correlated with the severity of the hearing loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16152638" 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 SIDEROBLASTIC ANEMIA, ACQUIRED IDIOPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, AISA6742C
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199476126 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199476126;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=rs199476126" 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=rs199476126" 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=RCV000010302 OR RCV002247303 OR RCV003985256" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010302, RCV002247303, RCV003985256" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010302...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mitochondrial iron overload in acquired idiopathic sideroblastic anemia (AISA) may be attributable to mutations of mitochondrial DNA because these can cause respiratory chain dysfunction, thereby impairing reduction of ferric iron to ferrous iron. The reduced form of iron is essential to the last step of mitochondrial heme biosynthesis. In 2 patients with AISA, <a href="#13" class="mim-tip-reference" title="Gattermann, N., Retzlaff, S., Wang, Y.-L., Hofhaus, G., Heinisch, J., Aul, C., Schneider, W. <strong>Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia.</strong> Blood 90: 4961-4972, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9389715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9389715</a>]" pmid="9389715">Gattermann et al. (1997)</a> identified point mutations of mtDNA affecting the same transmembrane helix within subunit I of cytochrome c oxidase. The mutations were detected by restriction fragment length polymorphism analysis and temperature gradient gel electrophoresis. The mutation in 1 patient was a T-to-C transition at nucleotide 6742, causing an amino acid change from methionine to threonine. The other patient had a T-to-C transition mutation at nucleotide 6721, changing isoleucine to threonine (see <a href="#0003">516030.0003</a>). Both amino acids are highly conserved in a wide range of species. Both mutations were heteroplasmic. They were present in bone marrow and whole blood samples, in isolated platelets, and in granulocytes, but appeared to be absent from T and B lymphocytes purified by immunomagnetic bead separation. They were not detected in either patient's buccal mucosa cells obtained by mouthwashes or in cultured skin fibroblasts derived from 1 of the patients. This pattern of involvement suggested that the mtDNA mutations in both patients occurred in a self-renewing bone marrow stem cell with myeloid determination. The identification of 2 point mutations with a very similar location suggested that cytochrome c oxidase plays an important role in the pathogenesis of AISA. Cytochrome c oxidase subunit I may be the physiologic site of iron reduction and transport through the inner mitochondrial membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9389715" 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 SIDEROBLASTIC ANEMIA, ACQUIRED IDIOPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, AISA6721C
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199476127 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199476127;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=rs199476127" 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=rs199476127" 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=RCV000010303 OR RCV004791205" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010303, RCV004791205" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010303...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See <a href="#0002">516030.0002</a> and <a href="#13" class="mim-tip-reference" title="Gattermann, N., Retzlaff, S., Wang, Y.-L., Hofhaus, G., Heinisch, J., Aul, C., Schneider, W. <strong>Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia.</strong> Blood 90: 4961-4972, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9389715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9389715</a>]" pmid="9389715">Gattermann et al. (1997)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9389715" 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 CYTOCHROME c OXIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, COX6480A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199476128 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199476128;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=rs199476128" 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=rs199476128" 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=RCV000010304 OR RCV000853974 OR RCV003985072" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010304, RCV000853974, RCV003985072" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010304...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#22" class="mim-tip-reference" title="Jaksch, M., Hofmann, S., Kleinle, S., Liechti-Gallati, S., Pongratz, D. E., Muller-Hocker, J., Jedele, K. B., Meitinger, T., Gerbitz, K.-D. <strong>A systematic mutation screen of 10 nuclear and 25 mitochondrial candidate genes in 21 patients with cytochrome c oxidase (COX) deficiency shows tRNA-ser(UCN) mutations in a subgroup with syndromal encephalopathy.</strong> J. Med. Genet. 35: 895-900, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9832034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9832034</a>] [<a href="https://doi.org/10.1136/jmg.35.11.895" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9832034">Jaksch et al. (1998)</a> identified a G-to-A transition at nucleotide 6480 of the MTCO1 gene in a child, her mother, and sister with cytochrome c oxidase deficiency (<a href="/entry/220110">220110</a>) associated with sensorineural hearing loss, ataxia, myoclonic epilepsy, and mental retardation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9832034" 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 COLORECTAL CANCER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, GLY121TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606882 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606882;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=rs267606882" 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=rs267606882" 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=RCV000010305 OR RCV000853954" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010305, RCV000853954" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010305...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Early on, <a href="#46" class="mim-tip-reference" title="Warburg, O. <strong>On the origin of cancer cells.</strong> Science 123: 309-314, 1956.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13298683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13298683</a>] [<a href="https://doi.org/10.1126/science.123.3191.309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13298683">Warburg (1956)</a> suggested that alterations of oxidative phosphorylation in tumor cells play a causative role in cancerous growth. Interest in the mitochondria with regard to neoplasia has revived, largely because of their role in apoptosis and other aspects of tumor biology. The mitochondrial genome is particularly susceptible to mutations because of the high level of reactive oxygen species (ROS) generated in this organelle, coupled with a low level of DNA repair. In a colorectal cancer (<a href="/entry/114500">114500</a>) cell line, <a href="#36" class="mim-tip-reference" title="Polyak, K., Li, Y., Zhu, H., Lengauer, C., Willson, J. K. V., Markowitz, S. D., Trush, M. A., Kinzler, K. W., Vogelstein, B. <strong>Somatic mutations of the mitochondrial genome in human colorectal tumours.</strong> Nature Genet. 20: 291-293, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9806551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9806551</a>] [<a href="https://doi.org/10.1038/3108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9806551">Polyak et al. (1998)</a> found a 6264G-A transition in the MTCO1 gene, resulting in truncation of the gene product as a result of a nonsense mutation changing gly121 to stop. The mitochondrial chromosome also contained insertion of an additional adenine after nucleotide 12418 in the lys28 codon of the MTND5 gene, resulting in frameshift. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9806551+13298683" 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 CYTOCHROME c OXIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, 6930G-A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28679680 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28679680;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=rs28679680" 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=rs28679680" 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=RCV000010306 OR RCV003985257" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010306, RCV003985257" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010306...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a young woman with a multisystem mitochondrial disorder and cytochrome c oxidase deficiency (<a href="/entry/220110">220110</a>), <a href="#7" class="mim-tip-reference" title="Bruno, C., Martinuzzi, A., Tang, Y., Andreu, A. L., Pallotti, F., Bonilla, E., Shanske, S., Fu, J., Sue, C. M., Angelini, C., DiMauro, S., Manfredi, G. <strong>A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV.</strong> Am. J. Hum. Genet. 65: 611-620, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441567</a>] [<a href="https://doi.org/10.1086/302546" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441567">Bruno et al. (1999)</a> identified a heteroplasmic G-to-A transition at nucleotide 6930 of the MTCO1 gene. The mutation changed a glycine codon to a stop codon, resulting in the predicted loss of the last 170 amino acids (33%) of the polypeptide. The mutation was present in the patient's muscle, myoblasts, and blood. It was not detected in mtDNA from leukocytes of the patient's mother, sister, and 4 maternal aunts. <a href="#7" class="mim-tip-reference" title="Bruno, C., Martinuzzi, A., Tang, Y., Andreu, A. L., Pallotti, F., Bonilla, E., Shanske, S., Fu, J., Sue, C. M., Angelini, C., DiMauro, S., Manfredi, G. <strong>A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV.</strong> Am. J. Hum. Genet. 65: 611-620, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441567</a>] [<a href="https://doi.org/10.1086/302546" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441567">Bruno et al. (1999)</a> studied the genetic, biochemical, and morphologic characteristics of trans-mitochondrial cybrid cell lines, obtained by fusing platelets from the patient with human cells lacking endogenous mtDNA. There was a direct relationship between the proportion of mutant mtDNA and the biochemical defect. They also observed that the threshold for the phenotypic expression of this mutation was lower than that reported in mutations involving tRNA genes. <a href="#7" class="mim-tip-reference" title="Bruno, C., Martinuzzi, A., Tang, Y., Andreu, A. L., Pallotti, F., Bonilla, E., Shanske, S., Fu, J., Sue, C. M., Angelini, C., DiMauro, S., Manfredi, G. <strong>A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV.</strong> Am. J. Hum. Genet. 65: 611-620, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441567</a>] [<a href="https://doi.org/10.1086/302546" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441567">Bruno et al. (1999)</a> suggested that this mutation causes a disruption in the assembly of the respiratory-chain complex IV. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441567" 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 MYOGLOBINURIA, RECURRENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, 5920G-A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs199476129 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199476129;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=rs199476129" 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=rs199476129" 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=RCV000010307 OR RCV003985258" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010307, RCV003985258" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010307...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#25" class="mim-tip-reference" title="Karadimas, C. L., Greenstein, P., Sue, C. M., Joseph, J. T., Tanji, K., Haller, R. G., Taivassalo, T., Davidson, M. M., Shanske, S., Bonilla, E., DiMauro, S. <strong>Recurrent myoglobinuria due to a nonsense mutation in the COX I gene of mitochondrial DNA.</strong> Neurology 55: 644-649, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10980727/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10980727</a>] [<a href="https://doi.org/10.1212/wnl.55.5.644" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10980727">Karadimas et al. (2000)</a> identified a G-to-A substitution at mitochondrial nucleotide 5920 resulting in a trp-to-ter mutation in the MTCO1 gene. The mutation was identified only in COX-deficient skeletal muscle fibers from a 33-year-old man who suffered from recurrent myoglobinuria since childhood. Serum CPK levels ranged from 15,000 to 38,000. The mutation was heteroplasmic and abundantly present in COX-negative fibers but less abundant or absent in COX-positive fibers; it was not found in blood or fibroblasts from the patient or in blood samples from the patient's asymptomatic mother and sister. The sporadic occurrence of this mutation in muscle alone suggested that it arose de novo in myogenic stem cells after germ-layer differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10980727" 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 CYTOCHROME c OXIDASE I DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, LEU196ILE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28461189 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28461189;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=rs28461189" 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=rs28461189" 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=RCV000010308 OR RCV000853976" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010308, RCV000853976" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010308...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#41" class="mim-tip-reference" title="Varlamov, D. A., Kudin, A. P., Vielhaber, S., Schroder, R., Sassen, R., Becker, A., Kunz, D., Haug, K., Rebstock, J., Heils, A., Elger, C. E., Kunz, W. S. <strong>Metabolic consequences of a novel missense mutation of the mtDNA CO I gene.</strong> Hum. Molec. Genet. 11: 1797-1805, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12140182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12140182</a>] [<a href="https://doi.org/10.1093/hmg/11.16.1797" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12140182">Varlamov et al. (2002)</a> identified a heteroplasmic 6489C-A missense mutation in the MTCO1 gene in a 17-year-old girl with epilepsia partialis continua. The point mutation led to a substitution of ile at the highly conserved leu196 (L196I). Muscle biopsy showed in single fibers decreased COX activity and lowered binding of COX antibodies, suggesting decreased stability of the mutated enzyme. Quantitative analysis of the mutation gene dosage effect on COX activity on single muscle fiber level revealed a very high threshold; a COX deficiency (see <a href="/entry/220110">220110</a>) was observed only in fibers containing more than 95% mutant mtDNA. In apparent contrast to this high mutation gene dosage threshold, in vivo investigations of mitochondrial function in saponin-permeabilized muscle fibers containing approximately 90% mutated mtDNA showed decreased maximal rates of respiration and an increased sensitivity of fiber respiration to cyanide. This was due to a 2-fold increase of COX flux control on muscle fiber respiration and a 30% decrease of COX metabolic threshold, supporting the concept of tight COX control of oxidative phosphorylation in skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12140182" 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 CYTOCHROME c OXIDASE I DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, SER142PHE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606883 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606883;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=rs267606883" 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=rs267606883" 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=RCV000010309" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010309" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010309</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In skeletal muscle tissue from a woman with COX deficiency (<a href="/entry/220110">220110</a>), <a href="#27" class="mim-tip-reference" title="Lucioli, S., Hoffmeier, K., Carrozzo, R., Tessa, A., Ludwig, B., Santorelli, F. M. <strong>Introducing a novel human mtDNA mutation into the Paracoccus denitrificans COX I gene explains functional deficits in a patient.</strong> Neurogenetics 7: 51-57, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16284789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16284789</a>] [<a href="https://doi.org/10.1007/s10048-005-0015-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16284789">Lucioli et al. (2006)</a> identified a homoplasmic 6328C-T transition in the MTCO1 gene, resulting in a ser142-to-phe (S142F) substitution in the beginning of the fourth N-terminal transmembrane helix. Expression of the homologous mutation in the bacterium Paracoccus denitrificans resulted in a significant decrease in COX enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16284789" 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 COLORECTAL CANCER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, GLY125ASP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs281865417 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865417;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=rs281865417" 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=rs281865417" 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=RCV000010310" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010310" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010310</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In colonocytes from cytochrome c oxidase-deficient crypts from a patient with colon cancer (<a href="/entry/114500">114500</a>), <a href="#15" class="mim-tip-reference" title="Greaves, L. C., Preston, S. L., Tadrous, P. J., Taylor, R. W., Barron, M. J., Oukrif, D., Leedham, S. J., Deheragoda, M., Sasieni, P., Novelli, M. R., Jankowski, J. A. Z., Turnbull, D. M., Wright, N. A., McDonald, S. A. C. <strong>Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission.</strong> Proc. Nat. Acad. Sci. 103: 714-719, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16407113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16407113</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16407113[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/10.1073/pnas.0505903103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16407113">Greaves et al. (2006)</a> identified a 6277A-G transition in the MTCO1 gene, predicted to result in a gly125-to-asp (G125D) substitution at a well-conserved residue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16407113" 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="#29" class="mim-tip-reference" title="Namslauer, I., Brzezinski, P. <strong>A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase.</strong> Proc. Nat. Acad. Sci. 106: 3402-3407, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19218458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19218458</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19218458[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/10.1073/pnas.0811450106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19218458">Namslauer and Brzezinski (2009)</a> used site-directed mutagenesis to alter the residue corresponding to gly125 in the MTCO1 gene of the bacterium Rhodobacter sphaeroides (G171D), and demonstrated that G171D-mutant COX displayed steady-state catalytic activity linked to proton pumping that was approximately 34% of wildtype. In addition, an intrinsic proton leak was found in the enzyme, which would lead to decreased overall energy-conversion efficiency of the respiratory chain, perturbing transport processes such as protein, ion, and metabolite trafficking. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19218458" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 COLORECTAL CANCER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
MTCO1, SER458PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606884 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606884;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=rs267606884" 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=rs267606884" 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=RCV000010311" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010311" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010311</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In colonocytes from cytochrome c oxidase-deficient crypts from a patient with colon cancer (<a href="/entry/114500">114500</a>), <a href="#15" class="mim-tip-reference" title="Greaves, L. C., Preston, S. L., Tadrous, P. J., Taylor, R. W., Barron, M. J., Oukrif, D., Leedham, S. J., Deheragoda, M., Sasieni, P., Novelli, M. R., Jankowski, J. A. Z., Turnbull, D. M., Wright, N. A., McDonald, S. A. C. <strong>Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission.</strong> Proc. Nat. Acad. Sci. 103: 714-719, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16407113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16407113</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16407113[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/10.1073/pnas.0505903103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16407113">Greaves et al. (2006)</a> identified a 7275T-C transition in the MTCO1 gene, predicted to result in a ser458-to-pro (S458P) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16407113" 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="#29" class="mim-tip-reference" title="Namslauer, I., Brzezinski, P. <strong>A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase.</strong> Proc. Nat. Acad. Sci. 106: 3402-3407, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19218458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19218458</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19218458[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/10.1073/pnas.0811450106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19218458">Namslauer and Brzezinski (2009)</a> used site-directed mutagenesis to alter the residue corresponding to ser458 in the MTCO1 gene of the bacterium Rhodobacter sphaeroides (A501P), and found that A501P-mutant COX was not expressed, indicating that the amino acid substitution results in a severely altered overall structure of the enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19218458" 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="#Brown1992" class="mim-tip-reference" title="Brown, M. D., Yang, C.-C., Trounce, I., Torroni, A., Lott, M. T., Wallace, D. C. <strong>A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I.</strong> Am. J. Hum. Genet. 51: 378-385, 1992.">Brown et al. (1992)</a>; <a href="#Montoya1981" class="mim-tip-reference" title="Montoya, J., Ojala, D., Attardi, G. <strong>Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs.</strong> Nature 290: 465-470, 1981.">Montoya 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="Acin-Perez2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Acin-Perez, R., Bayona-Bafaluy, M. P., Bueno, M., Machicado, C., Fernandez-Silva, P., Perez-Martos, A., Montoya, J., Lopez-Perez, M. J., Sancho, J., Enriquez, J. A.
|
|
<strong>An intragenic suppressor in the cytochrome c oxidase I gene of mouse mitochondrial DNA.</strong>
|
|
Hum. Molec. Genet. 12: 329-339, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12554686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12554686</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12554686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddg021" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Anderson1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G.
|
|
<strong>Sequence and organization of the human mitochondrial genome.</strong>
|
|
Nature 290: 457-465, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/290457a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Attardi1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Attardi, G., Chomyn, A., Montoya, J., Ojala, D.
|
|
<strong>Identification and mapping of human mitochondrial genes.</strong>
|
|
Cytogenet. Cell Genet. 32: 85-98, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7140372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7140372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7140372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000131689" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Brown1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, M. D., Voljavec, A. S., Lott, M. T., MacDonald, I., Wallace, D. C.
|
|
<strong>Leber's hereditary optic neuropathy; a model for mitochondrial neurodegenerative diseases.</strong>
|
|
FASEB J. 6: 2791-2799, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1634041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1634041</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1634041" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1096/fasebj.6.10.1634041" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Brown1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, M. D., Wallace, D. C.
|
|
<strong>Molecular basis of mitochondrial DNA disease.</strong>
|
|
J. Bioenerg. Biomembr. 26: 263-279, 1994.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Brown1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, M. D., Yang, C.-C., Trounce, I., Torroni, A., Lott, M. T., Wallace, D. C.
|
|
<strong>A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I.</strong>
|
|
Am. J. Hum. Genet. 51: 378-385, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1322638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1322638</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1322638" 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="7" class="mim-anchor"></a>
|
|
<a id="Bruno1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bruno, C., Martinuzzi, A., Tang, Y., Andreu, A. L., Pallotti, F., Bonilla, E., Shanske, S., Fu, J., Sue, C. M., Angelini, C., DiMauro, S., Manfredi, G.
|
|
<strong>A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV.</strong>
|
|
Am. J. Hum. Genet. 65: 611-620, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441567</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302546" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Capaldi1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Capaldi, R. A.
|
|
<strong>Structure and function of cytochrome c oxidase.</strong>
|
|
Annu. Rev. Biochem. 59: 569-596, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2165384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2165384</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2165384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1146/annurev.bi.59.070190.003033" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Case1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Case, J. T., Wallace, D. C.
|
|
<strong>Maternal inheritance of mitochondrial DNA polymorphisms in cultured human fibroblasts.</strong>
|
|
Somat. Cell Genet. 7: 103-108, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261411</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6261411" 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/BF01544751" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Ching1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ching, E., Attardi, G.
|
|
<strong>High-resolution electrophoretic fractionation and partial characterization of the mitochondrial translation products from HeLa cells.</strong>
|
|
Biochemistry 21: 3188-3195, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6285960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6285960</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6285960" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1021/bi00256a024" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Davis1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., Parker, W. D., Jr.
|
|
<strong>Mutations in mitochondrial cytosome c oxidase genes segregate with late-onset Alzheimer disease.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 4526-4531, 1997. Note: Retraction: Proc. Nat.Acad. Sci. 95: 12069 only, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9114023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9114023</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9114023" 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.94.9.4526" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Fan2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fan, W., Waymire, K. G., Narula, N., Li, P., Rocher, C., Coskun, P. E., Vannan, M. A., Narula, J., MacGregor, G. R., Wallace, D. C.
|
|
<strong>A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations.</strong>
|
|
Science 319: 958-962, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18276892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18276892</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18276892[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=18276892" 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.1147786" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Gattermann1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gattermann, N., Retzlaff, S., Wang, Y.-L., Hofhaus, G., Heinisch, J., Aul, C., Schneider, W.
|
|
<strong>Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia.</strong>
|
|
Blood 90: 4961-4972, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9389715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9389715</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9389715" 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="14" class="mim-anchor"></a>
|
|
<a id="Giles1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giles, R. E., Blanc, H., Cann, H. M., Wallace, D. C.
|
|
<strong>Maternal inheritance of human mitochondrial DNA.</strong>
|
|
Proc. Nat. Acad. Sci. 77: 6715-6719, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6256757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6256757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6256757" 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.77.11.6715" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Greaves2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Greaves, L. C., Preston, S. L., Tadrous, P. J., Taylor, R. W., Barron, M. J., Oukrif, D., Leedham, S. J., Deheragoda, M., Sasieni, P., Novelli, M. R., Jankowski, J. A. Z., Turnbull, D. M., Wright, N. A., McDonald, S. A. C.
|
|
<strong>Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 714-719, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16407113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16407113</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16407113[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=16407113" 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.0505903103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Guan1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guan, M.-X., Enriquez, J. A., Fischel-Ghodsian, N., Puranam, R. S., Lin, C. P., Maw, M. A., Attardi, G.
|
|
<strong>The deafness-associated mitochondrial DNA mutation at position 7445, which effects tRNA-ser(UCN) precursor processing, has long-range affects on NADH dehydrogenase subunit ND6 gene expression.</strong>
|
|
Molec. Cell. Biol. 18: 5868-5879, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9742104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9742104</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9742104[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=9742104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.18.10.5868" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Hare1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hare, J. F., Ching, E., Attardi, G.
|
|
<strong>Isolation, subunit composition and site of synthesis of human cytochrome c oxidase.</strong>
|
|
Biochemistry 19: 2023-2030, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6246917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6246917</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6246917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1021/bi00551a003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Hayashi2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hayashi, T., Asano, Y., Shintani, Y., Aoyama, H., Kioka, H., Tsukamoto, O., Hikita, M., Shinzawa-Itoh, K., Takafuji, K., Higo, S., Kato, H., Yamazaki, S., and 13 others.
|
|
<strong>Higd1a is a positive regulator of cytochrome c oxidase.</strong>
|
|
Proc. Nat. Acad. Sci. 112: 1553-1558, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25605899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25605899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25605899[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=25605899" 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.1419767112" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Hill1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hill, B. C.
|
|
<strong>The sequence of electron carriers in the reaction of cytochrome c oxidase with oxygen.</strong>
|
|
J. Bioenerg. Biomembr. 25: 115-120, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8389744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8389744</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8389744" 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/BF00762853" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Hirano1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hirano, M., Shtilbans, A., Mayeux, R., Davidson, M. M., DiMauro, S., Knowles, J. A., Schon, E. A.
|
|
<strong>Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 14894-14899, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9405710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9405710</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9405710[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=9405710" 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.94.26.14894" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Hosler1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hosler, J. P., Ferguson-Miller, S., Calhoun, M. W., Thomas, J. W., Hill, J., Lemieux, L., Ma, J., Georgiou, C., Fetter, J., Shapleigh, J., Tecklenburg, M. M. J., Babcock, G. T., Gennis, R. B.
|
|
<strong>Insight into the active-site structure and function of cytochrome oxidase by analysis of site-directed mutants of bacterial cytochrome aa3 and cytochrome bo.</strong>
|
|
J. Bioenerg. Biomembr. 25: 121-136, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8389745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8389745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8389745" 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/BF00762854" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Jaksch1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jaksch, M., Hofmann, S., Kleinle, S., Liechti-Gallati, S., Pongratz, D. E., Muller-Hocker, J., Jedele, K. B., Meitinger, T., Gerbitz, K.-D.
|
|
<strong>A systematic mutation screen of 10 nuclear and 25 mitochondrial candidate genes in 21 patients with cytochrome c oxidase (COX) deficiency shows tRNA-ser(UCN) mutations in a subgroup with syndromal encephalopathy.</strong>
|
|
J. Med. Genet. 35: 895-900, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9832034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9832034</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9832034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.35.11.895" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Johns1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Neufeld, M. J.
|
|
<strong>Cytochrome c oxidase mutations in Leber hereditary optic neuropathy.</strong>
|
|
Biochem. Biophys. Res. Commun. 196: 810-815, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8240356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8240356</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8240356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.1993.2321" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Kadenbach1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kadenbach, B., Jarausch, J., Hartmann, R., Merle, P.
|
|
<strong>Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoretic procedure.</strong>
|
|
Anal. Biochem. 129: 517-521, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6303162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6303162</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6303162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0003-2697(83)90586-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Karadimas2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Karadimas, C. L., Greenstein, P., Sue, C. M., Joseph, J. T., Tanji, K., Haller, R. G., Taivassalo, T., Davidson, M. M., Shanske, S., Bonilla, E., DiMauro, S.
|
|
<strong>Recurrent myoglobinuria due to a nonsense mutation in the COX I gene of mitochondrial DNA.</strong>
|
|
Neurology 55: 644-649, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10980727/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10980727</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10980727" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.55.5.644" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Lomax1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lomax, M. I., Grossman, L. I.
|
|
<strong>Tissue-specific genes for respiratory proteins.</strong>
|
|
Trends Biochem. Sci. 14: 501-503, 1989. Note: Erratum: Trends Biochem. Sci. 15: 217 only, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2560276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2560276</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2560276" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0968-0004(89)90185-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Lucioli2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lucioli, S., Hoffmeier, K., Carrozzo, R., Tessa, A., Ludwig, B., Santorelli, F. M.
|
|
<strong>Introducing a novel human mtDNA mutation into the Paracoccus denitrificans COX I gene explains functional deficits in a patient.</strong>
|
|
Neurogenetics 7: 51-57, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16284789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16284789</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16284789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10048-005-0015-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Montoya1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montoya, J., Ojala, D., Attardi, G.
|
|
<strong>Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs.</strong>
|
|
Nature 290: 465-470, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219535</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/290465a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Namslauer2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Namslauer, I., Brzezinski, P.
|
|
<strong>A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 3402-3407, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19218458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19218458</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19218458[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=19218458" 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.0811450106" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Ojala1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ojala, D., Montoya, J., Attardi, G.
|
|
<strong>tRNA punctuation model of RNA processing in human mitochondria.</strong>
|
|
Nature 290: 470-474, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219536</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/290470a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Oliver1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., McCarthy, J., Wallace, D. C.
|
|
<strong>Comparison of mitochondrially synthesized polypeptides of human, mouse, and monkey cell lines by a two-dimensional protease gel system.</strong>
|
|
Somat. Cell Molec. Genet. 10: 639-643, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438810</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6438810" 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/BF01535230" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Oliver1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., Wallace, D. C.
|
|
<strong>Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction.</strong>
|
|
Molec. Cell. Biol. 2: 30-41, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6955589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6955589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6955589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/mcb.2.1.30-41.1982" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Palmer1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Palmer, G.
|
|
<strong>Current issues in the chemistry of cytochrome c oxidase.</strong>
|
|
J. Bioenerg. Biomembr. 25: 145-151, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8389747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8389747</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8389747" 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/BF00762856" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Pandya1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pandya, A., Xia, X.-J., Erdenetungalag, R., Amendola, M., Landa, B., Radnaabazar, J., Dangaasuren, B., Van Tuyle, G., Nance, W. E.
|
|
<strong>Heterozygous point mutations in the mitochondrial tRNA Ser(UCN) precursor coexisting with the A1555G mutation in deaf students from Mongolia. (Letter)</strong>
|
|
Am. J. Hum. Genet. 65: 1803-1806, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10577941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10577941</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10577941[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=10577941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302658" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Parfait1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Parfait, B., Percheron, A., Chretien, D., Rustin, P., Munnich, A., Rotig, A.
|
|
<strong>No mitochondrial cytochrome oxidase (COX) gene mutations in 18 cases of COX deficiency.</strong>
|
|
Hum. Genet. 101: 247-250, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9402980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9402980</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9402980" 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/s004390050625" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Polyak1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Polyak, K., Li, Y., Zhu, H., Lengauer, C., Willson, J. K. V., Markowitz, S. D., Trush, M. A., Kinzler, K. W., Vogelstein, B.
|
|
<strong>Somatic mutations of the mitochondrial genome in human colorectal tumours.</strong>
|
|
Nature Genet. 20: 291-293, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9806551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9806551</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9806551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/3108" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Prochaska1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Prochaska, L. J., Bisson, R., Capaldi, R. A., Steffens, G. C., Buse, G.
|
|
<strong>Inhibition of cytochrome c oxidase function by dicyclohexylcarbodiimide.</strong>
|
|
Biochim. Biophys. Acta 637: 360-373, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6271198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6271198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6271198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0005-2728(81)90175-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Rousseau1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rousseau, D. L., Ching, Y., Wang, J.
|
|
<strong>Proton translocation in cytochrome c oxidase: redox linkage through proximal ligand exchange on cytochrome a3.</strong>
|
|
J. Bioenerg. Biomembr. 25: 165-176, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8389749/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8389749</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8389749" 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/BF00762858" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Shoffner1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shoffner, J. M., Wallace, D. C.
|
|
<strong>Oxidative phosphorylation diseases.In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic and Molecular Bases of Inherited Disease. Vol. 1. (7th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 1995. Pp. 1535-1609.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Temperley2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Temperley, R., Richter, R. Dennerlein, S., Lightowlers, R. N., Chrzanowska-Lightowlers, Z. M.
|
|
<strong>Hungry codons promote frameshifting in human mitochondrial ribosomes.</strong>
|
|
Science 327: 301 only, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20075246/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20075246</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20075246" 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.1180674" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Varlamov2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Varlamov, D. A., Kudin, A. P., Vielhaber, S., Schroder, R., Sassen, R., Becker, A., Kunz, D., Haug, K., Rebstock, J., Heils, A., Elger, C. E., Kunz, W. S.
|
|
<strong>Metabolic consequences of a novel missense mutation of the mtDNA CO I gene.</strong>
|
|
Hum. Molec. Genet. 11: 1797-1805, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12140182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12140182</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12140182" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/11.16.1797" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Wallace1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M.
|
|
<strong>Report of the committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong>
|
|
Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Wallace1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Stugard, C., Murdock, D., Schurr, T., Brown, M. D.
|
|
<strong>Ancient mtDNA sequences in the human nuclear genome: a potential source of errors in identifying pathogenic mutations.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 14900-14905, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9405711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9405711</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9405711[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=9405711" 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.94.26.14900" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Wallace1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Yang, J., Ye, J., Lott, M. T., Oliver, N. A., McCarthy, J.
|
|
<strong>Computer prediction of peptide maps: assignment of polypeptides to human and mouse mitochondrial DNA genes by analysis of two dimensional-proteolytic digest gels.</strong>
|
|
Am. J. Hum. Genet. 38: 461-481, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3518425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3518425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3518425" 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="45" class="mim-anchor"></a>
|
|
<a id="Wallace1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wallace, D. C.
|
|
<strong>Mitochondrial diseases: genotype versus phenotype.</strong>
|
|
Trends Genet. 9: 128-133, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8516847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8516847</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8516847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0168-9525(93)90207-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Warburg1956" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Warburg, O.
|
|
<strong>On the origin of cancer cells.</strong>
|
|
Science 123: 309-314, 1956.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13298683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13298683</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13298683" 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.123.3191.309" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Wisloff2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wisloff, U., Najjar, S. M., Ellingsen, O., Haram, P. M., Swoap, S., Al-Share, Q., Fernstrom, M., Rezaei, K., Lee, S. J., Koch, L. G., Britton, S. L.
|
|
<strong>Cardiovascular risk factors emerge after artificial selection for low aerobic capacity.</strong>
|
|
Science 307: 418-420, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15662013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15662013</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15662013" 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.1108177" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Yuan2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yuan, H., Qian, Y., Xu, Y., Cao, J., Bai, L., Shen, W., Ji, F., Zhang, X., Kang, D., Mo, J. Q., Greinwald, J. H., Han, D., Zhai, S., Young, W.-Y., Guan, M.-X.
|
|
<strong>Cosegregation of the G7444A mutation in the mitochondrial COI/tRNA-Ser(UCN) genes with the 12S rRNA A1555G mutation in a Chinese family with aminoglycoside-induced and nonsyndromic hearing loss.</strong>
|
|
Am. J. Med. Genet. 138A: 133-140, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16152638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16152638</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16152638[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=16152638" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.30952" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Bao Lige - updated : 10/14/2019
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 2/1/2010<br>Marla J. F. O'Neill - updated : 10/5/2009<br>Ada Hamosh - updated : 3/26/2008<br>Cassandra L. Kniffin - updated : 5/17/2006<br>Cassandra L. Kniffin - updated : 10/25/2005<br>Ada Hamosh - updated : 2/2/2005<br>George E. Tiller - updated : 1/3/2005<br>George E. Tiller - updated : 7/2/2003<br>Majed J. Dasouki - updated : 1/30/2001<br>Victor A. McKusick - updated : 9/23/1999<br>Victor A. McKusick - updated : 6/15/1999<br>Michael J. Wright - updated : 2/12/1999<br>Victor A. McKusick - updated : 3/26/1998<br>Victor A. McKusick - updated : 2/6/1998<br>Victor A. McKusick - updated : 12/2/1997<br>Douglas C. Wallace - updated : 4/6/1994
|
|
</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 : 3/2/1993
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 03/11/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
mgross : 10/14/2019<br>carol : 09/17/2018<br>carol : 07/08/2016<br>carol : 2/26/2013<br>mgross : 5/8/2012<br>carol : 5/24/2011<br>terry : 5/24/2011<br>wwang : 5/5/2010<br>ckniffin : 4/20/2010<br>carol : 3/3/2010<br>alopez : 2/2/2010<br>terry : 2/1/2010<br>carol : 1/19/2010<br>wwang : 10/14/2009<br>terry : 10/5/2009<br>ckniffin : 8/21/2009<br>alopez : 3/26/2008<br>wwang : 5/24/2006<br>ckniffin : 5/17/2006<br>wwang : 11/8/2005<br>ckniffin : 10/25/2005<br>alopez : 2/22/2005<br>alopez : 2/22/2005<br>terry : 2/2/2005<br>alopez : 1/3/2005<br>carol : 8/19/2003<br>carol : 7/10/2003<br>ckniffin : 7/8/2003<br>ckniffin : 7/7/2003<br>cwells : 7/2/2003<br>carol : 1/30/2001<br>mgross : 10/6/1999<br>terry : 9/23/1999<br>jlewis : 6/17/1999<br>terry : 6/15/1999<br>mgross : 3/4/1999<br>mgross : 3/1/1999<br>terry : 2/12/1999<br>dholmes : 5/11/1998<br>psherman : 3/26/1998<br>dholmes : 3/6/1998<br>mark : 2/15/1998<br>terry : 2/6/1998<br>mark : 12/9/1997<br>terry : 12/2/1997<br>mark : 6/23/1997<br>alopez : 6/18/1997<br>terry : 1/21/1997<br>mark : 4/9/1996<br>mark : 4/9/1996<br>mimman : 2/8/1996<br>mark : 6/19/1995<br>pfoster : 8/16/1994<br>mimadm : 4/26/1994<br>carol : 5/26/1993<br>carol : 5/17/1993
|
|
</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> 516030
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
COMPLEX IV, CYTOCHROME c OXIDASE SUBUNIT I; MTCO1
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
CYTOCHROME c OXIDASE I; CO1; COX1
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: MT-CO1</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 58610003, 67434000;
|
|
|
|
|
|
<strong>ICD10CM:</strong> H47.22;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</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>Cytochrome c oxidase subunit I (CO1 or MTCO1) is 1 of 3 mitochondrial DNA (mtDNA) encoded subunits (MTCO1, MTCO2, MTCO3) of respiratory Complex IV. Complex IV is located within the mitochondrial inner membrane and is the third and final enzyme of the electron transport chain of mitochondrial oxidative phosphorylation. It collects electrons from reduced cytochrome c and transfers them to oxygen to give water. The energy released is used to transport protons across the mitochondrial inner membrane. Complex IV is composed of 13 polypeptides. Subunits I, II, and III (MTCO1, MTCO2, MTCO3) are encoded by mtDNA while subunits IV, Va, Vb, VIa, VIb, VIc, VIIa, VIIb, VIIc, and VIII are nuclear encoded (Kadenbach et al., 1983; Shoffner and Wallace, 1995). While the mammalian Complex IV has a complex structure, several prokaryotic enzyme systems have the same catalytic functions, but are much simpler. These systems have been amenable to cloning and in vitro mutagenesis permitting detailed structure-function studies. Two well-studied systems are the cytochrome aa3 (cytochrome c oxidase) of Rhodobacter sphaeroides and the cytochrome bo (ubiquinol oxidase) of Escherichia coli. The R. sphaeroides enzyme has 3 subunits that are homologous to the 3 mammalian mtDNA subunits. R. sphaeroides subunit I is 62.1 kD and 52% identical and 76% similar to beef heart MTCO1; subunit II is 32.9 kD and 39% identical and 63% similar to beef MTCO2, and subunit III is 30.1 kD and 49% identical and 71% similar to beef heart. The Soret maxred = 444.5 nm (bovine = 443 nm) and alpha-band maxred = 606 nm (bovine = 604 nm). The extinction coefficients are identical (Hosler et al., 1993). These and other studies (Capaldi, 1990) have generated the following functional outlines for this enzyme. </p><p>The cytochrome c oxidase family of enzymes have 4 redox centers, 2 hemes and 2 copper centers. In mitochondrial Complex IV, the 2 hemes are a and a3 and the 2 coppers are CuA and CuB. The 2 hemes and CuB are bound to subunit I. For R. sphaeroides subunit I and for mammalian MTCO1, there are 12 membrane-spanning alpha-helices (I to XII). Of these helices, heme a is located between helix II and X, ligated with the invariant histidines at amino acid 102 (MTCO1 88) of helix II and at 421 (MTCO1 378) of helix X. Helix X lies between heme a and heme a3, with heme a3 bound to the opposite side of helix X at invariant histidine at amino acid 419 (MTCO1 376). Heme a3 is a component of a binuclear center which includes CuB and where oxygen is reduced to water. CuB is thought to lie adjacent to the iron of heme a3 and to be ligated to helix VI through invariant histidine 284 (MTCO1 240) and to helix VII through invariant histidines 333 and 334 (MTCO1 290 and 291). Amino acids histidine 411 (MTCO1 368), aspartate 412 (369), threonine 413 (370), and tyrosine 414 (371) occur in the conserved loop between helices IX and X, lying close to hemes a and a3, and may be in the proximity of the CuA located in subunit II (Hosler et al., 1993). </p><p>Subunit II of Complex IV interacts with cytochrome c and contains the CuA center. This means that the pathway of electron transfer through Complex IV is from cytochrome c, to CuA, to cytochrome a, and then to the binuclear center of cytochrome a3-CuB. It is thought that the transfer of electrons from cytochrome a to the binuclear center is the key control point in the reaction and one of the major points of energy transduction (Hill, 1993). </p><p>Proton translocation in Complex IV involves four electrons to reduce O2 and four protons taken up from the matrix side of the mitochondrial membrane for the formation of H2O. Four more protons are vertically translocated from the matrix to the cytosol side of the membrane. Evidence is accumulating that proton translocation is linked to electron transfer at the binuclear oxygen (O2) binding site, which has been extended to suggest that proton translocation is associated with proximal ligand exchange between tyrosine and histidine on cytochrome a3 (Rousseau et al., 1993). </p><p>The toxicity of classical inhibitors of Complex IV is the result of drug interaction with these reactive sites. Cyanide and azide form a bridge between cytochrome a3 and CuB. Thiocyanate and formate bind elsewhere on the binuclear center, probably at CuB (Palmer, 1993). </p><p>Subunit III is an universal component of cytochrome c oxidase. Previously, it was thought to participate in proton translocation because dicyclohexylcarbodiimide (DCCD), a inhibitor of proton transport in other systems, binds to the glutamate at position 90 in subunit III (Prochaska et al., 1981). However, more recent studies place this function at the binuclear center in subunit I. Hence, the function of subunit III remains unclear. </p><p>The functions of the 10 nuclear encoded Complex IV subunits is just beginning to be elucidated. Three of the subunits, VIa, VIIa, and VIII, have two isoforms, one expressed in heart and skeletal muscle and the other in the remaining tissues (Capaldi, 1990; Lomax and Grossman, 1989). The differential expression of this genes is in part the product of differential transcription (Wallace, 1993). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>MTCO1 is encoded by the guanine-rich heavy (H) strand of the mtDNA and located between nucleotide pairs (nps) 5904 and 7444 (Anderson et al., 1981; Wallace et al., 1994). It is maternally inherited along with the mtDNA (Giles et al., 1980; Case and Wallace, 1981). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The MTCO1 gene encompasses 1540 nps of continuous mtDNA which lacks introns and encodes a single polypeptide. The mRNA begins with a 12-np 5-prime nontranslated sequence, then the AUG start codon, the polypeptide coding sequence which ends in an AGA codon which serves as a stop codon, and the extends 72 nps through the antisense tRNAser(UCN) that serves as a 3-prime nontranslated region (Ojala et al., 1981; Attardi et al., 1982). The MTCO1 gene is transcribed as a part of the polycistronic H-strand transcript flanked by tRNAtyr at the 5-prime end and tRNAasp at the 3-prime end. Then these tRNAs are cleaved out of the transcript freeing transcript 9, the mRNA for MTCO1. The mRNA is then polyadenylated (Anderson et al., 1981; Ojala et al., 1981; Attardi et al., 1982). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The predicted molecular weight (MW) of MTCO1 is 57 kD (Anderson et al., 1981; Wallace et al., 1994). However, its apparent MW on SDS-polyacrylamide gels (PAGE) is somewhat less. Using Tris-glycine buffer it runs at 39.5 kD (Oliver et al., 1984; Oliver and Wallace, 1982; Wallace et al., 1986), whereas using urea-phosphate gives an apparent MW of 45 kD (Ching and Attardi, 1982; Hare et al., 1980). </p><p>Acin-Perez et al. (2003) identified a cell line containing single and double missense mutations in the cytochrome c oxidase (COX) subunit I gene of mouse mitochondrial DNA. When present in homoplasmy, the single mutant displayed a normal complex IV assembly but a significantly reduced COX activity, while the double mutant almost completely compensated the functional defect of the first mutation. The authors hypothesized that deleterious mutations can arise and become predominant; cultured cells can maintain several mtDNA haplotypes at stable frequencies; the respiratory chain has little spare COX capacity; and that the size of a cavity in the vicinity of val421 in MTCO1I of animal COX may affect the function of the enzyme. </p><p>Wisloff et al. (2005) hypothesized that artificial selection of rats based on low and high intrinsic exercise capacity would yield models that also contrast for cardiovascular disease risk. After 11 generations, rats with low aerobic capacity scored higher on cardiovascular risk factors that constitute the metabolic syndrome. The decrease in aerobic capacity was associated with decreases in the amounts of transcription factors required for mitochondrial biogenesis and in the amounts of oxidative enzymes in skeletal muscle. Wisloff et al. (2005) found that the amount of PPARG (601487), PPARG coactivator-1-alpha (PPARGC1A; 604517), ubiquinol-cytochrome c oxidoreductase core 2 subunit (UQCRC2; 191329), cytochrome c oxidase subunit I (MTCO1), uncoupling protein-2 (UCP2; 601693), and ATP synthase H(+)-transporting mitochondrial F1 complex (F1-ATP synthase; see 108729) were markedly reduced in the low capacity runner rats in comparison with the high capacity runners. The uniform decline in these proteins was consistent with the hypothesis that reduced aerobic metabolism plays a causal role in the development of the differences between the low capacity runner and high capacity runner rats. Wisloff et al. (2005) concluded that impairment of mitochondrial function may link reduced fitness to cardiovascular and metabolic disease. </p><p>Temperley et al. (2010) demonstrated that human mitoribosomes do invoke -1 frameshift at the AGA and AGG codons predicted to terminate the 2 ORFs in MTCO1 and MTND6 (516006), respectively. As a consequence, both ORFs terminate in the standard UAG codon, necessitating the use of only a single mitochondrial release factor. </p><p>By immunoblot analysis, Hayashi et al. (2015) showed that Higd1a (618623) expression was induced early in rat cardiomyocytes exposed to hypoxia. Immunoprecipitation analysis revealed that Higd1a directly associated with cytochrome c oxidase (CcO) and integrated into the CcO macromolecular complex, causing structural changes at heme a, the active center of CcO. Knockdown and overexpression analyses demonstrated that Higd1a positively regulated CcO activity and increased mitochondrial ATP production, thereby protecting cardiomyocytes against hypoxia. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Restriction site polymorphisms have been identified at the following nucleotide positions for the indicated enzymes (where '+' = site gain, '-' = site loss relative to the reference sequence, Anderson et al., 1981): Alu I: -5978, -5996, -6022, -6204, -6867, +7025, -7055; Ava II: +5984, +6332, +6581, +6699 (or 8719 or 8723); Dde I: -6296, +6356, -6377, -7103; Hae III: -6027, -6260, +6425, +6534, +6618, -6957, +7325, +7347; Hha I: -5971, +6166 or 6168; HinfI: -5983, -6211, +6610, -6871, -6931; Mbo I: -6904; Msp I: +6501, -6688, +7159; Pst I:-6910; Rsa I: +5985, +6915, -7013, +7241; Taq I: +6049 or 7854, -7335; Xba I: -7440 (Wallace et al., 1994). </p><p>One phenotypically relevant mutation localized to MTCO1 contributes to the etiology of Leber hereditary optic neuropathy (LHON; 535000) and is designated MTCO1*LHON7444A (516030.0001).</p><p>Davis et al. (1997) reported that 2 mitochondrial genes, the MTCO1 gene and the MTCO2 gene (516040), encoding CO subunits I and II, respectively, appeared to be associated with late-onset Alzheimer disease (see 502500); however, their work was later retracted. Prior to the retraction, Hirano et al. (1997) had noted that the DNA isolation method used by Davis et al. (1997) resulted in the coamplification of both authentic mtDNA-encoded COX genes and highly similar COX-like sequences embedded in nuclear DNA ('mtDNA pseudogenes'). Hirano et al. (1997) concluded that the observed heteroplasmy was an artifact. Wallace et al. (1997) had come to a similar conclusion. Using the same PCR primers utilized by Davis et al. (1997) to amplify CO1 and CO2 sequences from 2 independent mtDNA-less cell lines, they could amplify CO1 and CO2 sequences from both, demonstrating that these sequences are also present in the human nuclear DNA. Furthermore, they found all 5 of the mutations found by Davis et al. (1997) in addition to 32 single-base substitutions, including 2 in adjacent tRNAs, and a 2-bp deletion in the CO2 gene. Phylogenetic analysis of the nuclear CO1 and CO2 sequences revealed that they diverges from modern human mtDNAs early in the hominid evolution about 770,000 years before the present. </p><p>Deficiency of cytochrome c oxidase (COX) causes a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders in childhood and adulthood and theoretically can result from either nuclear or mitochondrial mutations with obvious differences in mode of inheritance (see 220110). Parfait et al. (1997) sequenced the 3 mitochondrially encoded COX subunits of complex IV to test for causative mutations in these genes. The study was performed in a series of 18 patients with isolated COX deficiency. They failed to detect any deleterious mutations in this series. Moreover, no mtDNA deletion was observed and sequencing of the flanking tRNA gene involved in the maturation of the COX transcripts failed to detect deleterious mutations as well. Their study supported the view that the disease-causing mutations do not lie in the mitochondrial genome but rather in the nuclear genes encoding either the COX subunits or the proteins involved in assembly of the complex. The results suggested further that a recurrence risk of 25% (as for an autosomal recessive mode of inheritance) can be used in genetic counseling of COX deficiencies. </p><p>Most mtDNA mutations that cause human disease are mild to moderately deleterious, yet many random mtDNA changes would be expected to be severe. To determine the fate of the more severe mtDNA mutations, Fan et al. (2008) introduced mtDNAs containing 2 mutations that affect oxidative phosphorylation, one mild and one severe, into the female mouse germ line. The severe mutation, 13885insC, created a frameshift mutation in the ND6 gene (516006). When homoplasmic, this mutation inactivates oxidative phosphorylation complex I. The mild mutation was a missense mutation, T6589C, in the COI gene that converted the highly conserved valine at codon 421 to alanine (V421A). When homoplasmic, this mutation reduces the activity of oxidative phosphorylation complex IV by 50%. Fan et al. (2008) observed that the severe ND6 mutation was selectively eliminated during oogenesis within 4 generations, whereas the milder COI mutation was retained throughout multiple generations even though the offspring consistently developed mitochondrial myopathy and cardiomyopathy. Thus, Fan et al. (2008) concluded that severe mitochondrial DNA mutations appear to be selectively eliminated from the female germ line, thereby minimizing their impact on population fitness. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>11 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 LEBER OPTIC ATROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
DEAFNESS, AMINOGLYCOSIDE-INDUCED, INCLUDED<br />
|
|
DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, LHON7444A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199474822,
|
|
|
|
|
|
|
|
ClinVar: RCV000010299, RCV000010300, RCV000010301, RCV000854073, RCV001268422, RCV003319164
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 535000. This allele converts the AGA termination codon to a lysine codon (AAA), permitting extension of the MTCO1 polypeptide by 3 amino acids (lysine, glutamine, lysine) into the antisense tRNAser(UCN) sequence (Brown et al., 1992; Johns and Neufeld, 1993). The mutation is associated with an impaired mobility of the polypeptide on SDS-PAGE and a 36% reduction in Complex IV activity in patient lymphoblasts. Patients with this mutation cluster within the Caucasian mtDNA phylogenetic tree (Brown et al., 1992). However, the 2 cases that have been extensively studied also harbor other LHON mutations: the MTND1*LHON3460A mutation in one case and the MTND6*LHON14484A in the other. Hence, the MTCO1*LHON7444A mutation is probably a secondary LHON mutation (Brown and Wallace, 1994). In the 2 families that harbored this mutation, between 23 and 43% of the maternal relatives were affected with all the affected individuals being male (Brown, Lott and Wallace, unpublished data). </p><p>Pandya et al. (1999) reported 6 unrelated Mongolian deaf students with cosegregation of a 7444G-A mutation and a 1555A-G mutation in the MTRNR1 gene (561000.0001). Five of the individuals had a family history consistent with matrilineal transmission of hearing loss (500008). Only 2 individuals had a definite history of aminoglycoside exposure, but all 6 had severe to profound bilateral sensorineural hearing loss detected at birth or in infancy. Pandya et al. (1999) suggested that the 7444G-A mutation would share a common pathogenic mechanism as the adjacent 7445A-G mutation (590080.0002) in the MTTS1 gene, which results in aberrant processing of the tRNA-ser(UCN) precursor (see Guan et al., 1998). </p><p>Yuan et al. (2005) reported cosegregation of a homoplasmic 7444G-A mutation and a homoplasmic 1555A-G MTRNR1 mutation in a 3-generation Chinese family with aminoglycoside-induced sensorineural hearing loss (580000). One additional family member with both mutations, who had a history of exposure to noise but not to aminoglycoside, exhibited mild hearing impairment. The dosage and age at the time of drug administration seemed to be correlated with the severity of the hearing loss. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 SIDEROBLASTIC ANEMIA, ACQUIRED IDIOPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, AISA6742C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199476126,
|
|
|
|
|
|
|
|
ClinVar: RCV000010302, RCV002247303, RCV003985256
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mitochondrial iron overload in acquired idiopathic sideroblastic anemia (AISA) may be attributable to mutations of mitochondrial DNA because these can cause respiratory chain dysfunction, thereby impairing reduction of ferric iron to ferrous iron. The reduced form of iron is essential to the last step of mitochondrial heme biosynthesis. In 2 patients with AISA, Gattermann et al. (1997) identified point mutations of mtDNA affecting the same transmembrane helix within subunit I of cytochrome c oxidase. The mutations were detected by restriction fragment length polymorphism analysis and temperature gradient gel electrophoresis. The mutation in 1 patient was a T-to-C transition at nucleotide 6742, causing an amino acid change from methionine to threonine. The other patient had a T-to-C transition mutation at nucleotide 6721, changing isoleucine to threonine (see 516030.0003). Both amino acids are highly conserved in a wide range of species. Both mutations were heteroplasmic. They were present in bone marrow and whole blood samples, in isolated platelets, and in granulocytes, but appeared to be absent from T and B lymphocytes purified by immunomagnetic bead separation. They were not detected in either patient's buccal mucosa cells obtained by mouthwashes or in cultured skin fibroblasts derived from 1 of the patients. This pattern of involvement suggested that the mtDNA mutations in both patients occurred in a self-renewing bone marrow stem cell with myeloid determination. The identification of 2 point mutations with a very similar location suggested that cytochrome c oxidase plays an important role in the pathogenesis of AISA. Cytochrome c oxidase subunit I may be the physiologic site of iron reduction and transport through the inner mitochondrial membrane. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 SIDEROBLASTIC ANEMIA, ACQUIRED IDIOPATHIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, AISA6721C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199476127,
|
|
|
|
|
|
|
|
ClinVar: RCV000010303, RCV004791205
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 516030.0002 and Gattermann et al. (1997). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CYTOCHROME c OXIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, COX6480A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199476128,
|
|
|
|
|
|
|
|
ClinVar: RCV000010304, RCV000853974, RCV003985072
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Jaksch et al. (1998) identified a G-to-A transition at nucleotide 6480 of the MTCO1 gene in a child, her mother, and sister with cytochrome c oxidase deficiency (220110) associated with sensorineural hearing loss, ataxia, myoclonic epilepsy, and mental retardation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 COLORECTAL CANCER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, GLY121TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606882,
|
|
|
|
|
|
|
|
ClinVar: RCV000010305, RCV000853954
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Early on, Warburg (1956) suggested that alterations of oxidative phosphorylation in tumor cells play a causative role in cancerous growth. Interest in the mitochondria with regard to neoplasia has revived, largely because of their role in apoptosis and other aspects of tumor biology. The mitochondrial genome is particularly susceptible to mutations because of the high level of reactive oxygen species (ROS) generated in this organelle, coupled with a low level of DNA repair. In a colorectal cancer (114500) cell line, Polyak et al. (1998) found a 6264G-A transition in the MTCO1 gene, resulting in truncation of the gene product as a result of a nonsense mutation changing gly121 to stop. The mitochondrial chromosome also contained insertion of an additional adenine after nucleotide 12418 in the lys28 codon of the MTND5 gene, resulting in frameshift. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 CYTOCHROME c OXIDASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, 6930G-A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28679680,
|
|
|
|
|
|
|
|
ClinVar: RCV000010306, RCV003985257
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a young woman with a multisystem mitochondrial disorder and cytochrome c oxidase deficiency (220110), Bruno et al. (1999) identified a heteroplasmic G-to-A transition at nucleotide 6930 of the MTCO1 gene. The mutation changed a glycine codon to a stop codon, resulting in the predicted loss of the last 170 amino acids (33%) of the polypeptide. The mutation was present in the patient's muscle, myoblasts, and blood. It was not detected in mtDNA from leukocytes of the patient's mother, sister, and 4 maternal aunts. Bruno et al. (1999) studied the genetic, biochemical, and morphologic characteristics of trans-mitochondrial cybrid cell lines, obtained by fusing platelets from the patient with human cells lacking endogenous mtDNA. There was a direct relationship between the proportion of mutant mtDNA and the biochemical defect. They also observed that the threshold for the phenotypic expression of this mutation was lower than that reported in mutations involving tRNA genes. Bruno et al. (1999) suggested that this mutation causes a disruption in the assembly of the respiratory-chain complex IV. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MYOGLOBINURIA, RECURRENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, 5920G-A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199476129,
|
|
|
|
|
|
|
|
ClinVar: RCV000010307, RCV003985258
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Karadimas et al. (2000) identified a G-to-A substitution at mitochondrial nucleotide 5920 resulting in a trp-to-ter mutation in the MTCO1 gene. The mutation was identified only in COX-deficient skeletal muscle fibers from a 33-year-old man who suffered from recurrent myoglobinuria since childhood. Serum CPK levels ranged from 15,000 to 38,000. The mutation was heteroplasmic and abundantly present in COX-negative fibers but less abundant or absent in COX-positive fibers; it was not found in blood or fibroblasts from the patient or in blood samples from the patient's asymptomatic mother and sister. The sporadic occurrence of this mutation in muscle alone suggested that it arose de novo in myogenic stem cells after germ-layer differentiation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CYTOCHROME c OXIDASE I DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, LEU196ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28461189,
|
|
|
|
|
|
|
|
ClinVar: RCV000010308, RCV000853976
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Varlamov et al. (2002) identified a heteroplasmic 6489C-A missense mutation in the MTCO1 gene in a 17-year-old girl with epilepsia partialis continua. The point mutation led to a substitution of ile at the highly conserved leu196 (L196I). Muscle biopsy showed in single fibers decreased COX activity and lowered binding of COX antibodies, suggesting decreased stability of the mutated enzyme. Quantitative analysis of the mutation gene dosage effect on COX activity on single muscle fiber level revealed a very high threshold; a COX deficiency (see 220110) was observed only in fibers containing more than 95% mutant mtDNA. In apparent contrast to this high mutation gene dosage threshold, in vivo investigations of mitochondrial function in saponin-permeabilized muscle fibers containing approximately 90% mutated mtDNA showed decreased maximal rates of respiration and an increased sensitivity of fiber respiration to cyanide. This was due to a 2-fold increase of COX flux control on muscle fiber respiration and a 30% decrease of COX metabolic threshold, supporting the concept of tight COX control of oxidative phosphorylation in skeletal muscle. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CYTOCHROME c OXIDASE I DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, SER142PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606883,
|
|
|
|
|
|
|
|
ClinVar: RCV000010309
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In skeletal muscle tissue from a woman with COX deficiency (220110), Lucioli et al. (2006) identified a homoplasmic 6328C-T transition in the MTCO1 gene, resulting in a ser142-to-phe (S142F) substitution in the beginning of the fourth N-terminal transmembrane helix. Expression of the homologous mutation in the bacterium Paracoccus denitrificans resulted in a significant decrease in COX enzyme activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 COLORECTAL CANCER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, GLY125ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs281865417,
|
|
|
|
|
|
|
|
ClinVar: RCV000010310
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In colonocytes from cytochrome c oxidase-deficient crypts from a patient with colon cancer (114500), Greaves et al. (2006) identified a 6277A-G transition in the MTCO1 gene, predicted to result in a gly125-to-asp (G125D) substitution at a well-conserved residue. </p><p>Namslauer and Brzezinski (2009) used site-directed mutagenesis to alter the residue corresponding to gly125 in the MTCO1 gene of the bacterium Rhodobacter sphaeroides (G171D), and demonstrated that G171D-mutant COX displayed steady-state catalytic activity linked to proton pumping that was approximately 34% of wildtype. In addition, an intrinsic proton leak was found in the enzyme, which would lead to decreased overall energy-conversion efficiency of the respiratory chain, perturbing transport processes such as protein, ion, and metabolite trafficking. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 COLORECTAL CANCER</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTCO1, SER458PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606884,
|
|
|
|
|
|
|
|
ClinVar: RCV000010311
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In colonocytes from cytochrome c oxidase-deficient crypts from a patient with colon cancer (114500), Greaves et al. (2006) identified a 7275T-C transition in the MTCO1 gene, predicted to result in a ser458-to-pro (S458P) substitution. </p><p>Namslauer and Brzezinski (2009) used site-directed mutagenesis to alter the residue corresponding to ser458 in the MTCO1 gene of the bacterium Rhodobacter sphaeroides (A501P), and found that A501P-mutant COX was not expressed, indicating that the amino acid substitution results in a severely altered overall structure of the enzyme. </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">
|
|
Brown et al. (1992); Montoya 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">
|
|
Acin-Perez, R., Bayona-Bafaluy, M. P., Bueno, M., Machicado, C., Fernandez-Silva, P., Perez-Martos, A., Montoya, J., Lopez-Perez, M. J., Sancho, J., Enriquez, J. A.
|
|
<strong>An intragenic suppressor in the cytochrome c oxidase I gene of mouse mitochondrial DNA.</strong>
|
|
Hum. Molec. Genet. 12: 329-339, 2003.
|
|
|
|
|
|
[PubMed: 12554686]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg021]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G.
|
|
<strong>Sequence and organization of the human mitochondrial genome.</strong>
|
|
Nature 290: 457-465, 1981.
|
|
|
|
|
|
[PubMed: 7219534]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/290457a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Attardi, G., Chomyn, A., Montoya, J., Ojala, D.
|
|
<strong>Identification and mapping of human mitochondrial genes.</strong>
|
|
Cytogenet. Cell Genet. 32: 85-98, 1982.
|
|
|
|
|
|
[PubMed: 7140372]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000131689]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, M. D., Voljavec, A. S., Lott, M. T., MacDonald, I., Wallace, D. C.
|
|
<strong>Leber's hereditary optic neuropathy; a model for mitochondrial neurodegenerative diseases.</strong>
|
|
FASEB J. 6: 2791-2799, 1992.
|
|
|
|
|
|
[PubMed: 1634041]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1096/fasebj.6.10.1634041]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, M. D., Wallace, D. C.
|
|
<strong>Molecular basis of mitochondrial DNA disease.</strong>
|
|
J. Bioenerg. Biomembr. 26: 263-279, 1994.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, M. D., Yang, C.-C., Trounce, I., Torroni, A., Lott, M. T., Wallace, D. C.
|
|
<strong>A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I.</strong>
|
|
Am. J. Hum. Genet. 51: 378-385, 1992.
|
|
|
|
|
|
[PubMed: 1322638]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bruno, C., Martinuzzi, A., Tang, Y., Andreu, A. L., Pallotti, F., Bonilla, E., Shanske, S., Fu, J., Sue, C. M., Angelini, C., DiMauro, S., Manfredi, G.
|
|
<strong>A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV.</strong>
|
|
Am. J. Hum. Genet. 65: 611-620, 1999.
|
|
|
|
|
|
[PubMed: 10441567]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302546]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Capaldi, R. A.
|
|
<strong>Structure and function of cytochrome c oxidase.</strong>
|
|
Annu. Rev. Biochem. 59: 569-596, 1990.
|
|
|
|
|
|
[PubMed: 2165384]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1146/annurev.bi.59.070190.003033]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Case, J. T., Wallace, D. C.
|
|
<strong>Maternal inheritance of mitochondrial DNA polymorphisms in cultured human fibroblasts.</strong>
|
|
Somat. Cell Genet. 7: 103-108, 1981.
|
|
|
|
|
|
[PubMed: 6261411]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01544751]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ching, E., Attardi, G.
|
|
<strong>High-resolution electrophoretic fractionation and partial characterization of the mitochondrial translation products from HeLa cells.</strong>
|
|
Biochemistry 21: 3188-3195, 1982.
|
|
|
|
|
|
[PubMed: 6285960]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1021/bi00256a024]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., Parker, W. D., Jr.
|
|
<strong>Mutations in mitochondrial cytosome c oxidase genes segregate with late-onset Alzheimer disease.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 4526-4531, 1997. Note: Retraction: Proc. Nat.Acad. Sci. 95: 12069 only, 1998.
|
|
|
|
|
|
[PubMed: 9114023]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.94.9.4526]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fan, W., Waymire, K. G., Narula, N., Li, P., Rocher, C., Coskun, P. E., Vannan, M. A., Narula, J., MacGregor, G. R., Wallace, D. C.
|
|
<strong>A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations.</strong>
|
|
Science 319: 958-962, 2008.
|
|
|
|
|
|
[PubMed: 18276892]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1147786]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gattermann, N., Retzlaff, S., Wang, Y.-L., Hofhaus, G., Heinisch, J., Aul, C., Schneider, W.
|
|
<strong>Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia.</strong>
|
|
Blood 90: 4961-4972, 1997.
|
|
|
|
|
|
[PubMed: 9389715]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giles, R. E., Blanc, H., Cann, H. M., Wallace, D. C.
|
|
<strong>Maternal inheritance of human mitochondrial DNA.</strong>
|
|
Proc. Nat. Acad. Sci. 77: 6715-6719, 1980.
|
|
|
|
|
|
[PubMed: 6256757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.77.11.6715]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Greaves, L. C., Preston, S. L., Tadrous, P. J., Taylor, R. W., Barron, M. J., Oukrif, D., Leedham, S. J., Deheragoda, M., Sasieni, P., Novelli, M. R., Jankowski, J. A. Z., Turnbull, D. M., Wright, N. A., McDonald, S. A. C.
|
|
<strong>Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 714-719, 2006.
|
|
|
|
|
|
[PubMed: 16407113]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0505903103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guan, M.-X., Enriquez, J. A., Fischel-Ghodsian, N., Puranam, R. S., Lin, C. P., Maw, M. A., Attardi, G.
|
|
<strong>The deafness-associated mitochondrial DNA mutation at position 7445, which effects tRNA-ser(UCN) precursor processing, has long-range affects on NADH dehydrogenase subunit ND6 gene expression.</strong>
|
|
Molec. Cell. Biol. 18: 5868-5879, 1998.
|
|
|
|
|
|
[PubMed: 9742104]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.18.10.5868]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hare, J. F., Ching, E., Attardi, G.
|
|
<strong>Isolation, subunit composition and site of synthesis of human cytochrome c oxidase.</strong>
|
|
Biochemistry 19: 2023-2030, 1980.
|
|
|
|
|
|
[PubMed: 6246917]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1021/bi00551a003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hayashi, T., Asano, Y., Shintani, Y., Aoyama, H., Kioka, H., Tsukamoto, O., Hikita, M., Shinzawa-Itoh, K., Takafuji, K., Higo, S., Kato, H., Yamazaki, S., and 13 others.
|
|
<strong>Higd1a is a positive regulator of cytochrome c oxidase.</strong>
|
|
Proc. Nat. Acad. Sci. 112: 1553-1558, 2015.
|
|
|
|
|
|
[PubMed: 25605899]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1419767112]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hill, B. C.
|
|
<strong>The sequence of electron carriers in the reaction of cytochrome c oxidase with oxygen.</strong>
|
|
J. Bioenerg. Biomembr. 25: 115-120, 1993.
|
|
|
|
|
|
[PubMed: 8389744]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00762853]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hirano, M., Shtilbans, A., Mayeux, R., Davidson, M. M., DiMauro, S., Knowles, J. A., Schon, E. A.
|
|
<strong>Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 14894-14899, 1997.
|
|
|
|
|
|
[PubMed: 9405710]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.94.26.14894]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hosler, J. P., Ferguson-Miller, S., Calhoun, M. W., Thomas, J. W., Hill, J., Lemieux, L., Ma, J., Georgiou, C., Fetter, J., Shapleigh, J., Tecklenburg, M. M. J., Babcock, G. T., Gennis, R. B.
|
|
<strong>Insight into the active-site structure and function of cytochrome oxidase by analysis of site-directed mutants of bacterial cytochrome aa3 and cytochrome bo.</strong>
|
|
J. Bioenerg. Biomembr. 25: 121-136, 1993.
|
|
|
|
|
|
[PubMed: 8389745]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00762854]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jaksch, M., Hofmann, S., Kleinle, S., Liechti-Gallati, S., Pongratz, D. E., Muller-Hocker, J., Jedele, K. B., Meitinger, T., Gerbitz, K.-D.
|
|
<strong>A systematic mutation screen of 10 nuclear and 25 mitochondrial candidate genes in 21 patients with cytochrome c oxidase (COX) deficiency shows tRNA-ser(UCN) mutations in a subgroup with syndromal encephalopathy.</strong>
|
|
J. Med. Genet. 35: 895-900, 1998.
|
|
|
|
|
|
[PubMed: 9832034]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.35.11.895]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Neufeld, M. J.
|
|
<strong>Cytochrome c oxidase mutations in Leber hereditary optic neuropathy.</strong>
|
|
Biochem. Biophys. Res. Commun. 196: 810-815, 1993.
|
|
|
|
|
|
[PubMed: 8240356]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1993.2321]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kadenbach, B., Jarausch, J., Hartmann, R., Merle, P.
|
|
<strong>Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoretic procedure.</strong>
|
|
Anal. Biochem. 129: 517-521, 1983.
|
|
|
|
|
|
[PubMed: 6303162]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0003-2697(83)90586-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Karadimas, C. L., Greenstein, P., Sue, C. M., Joseph, J. T., Tanji, K., Haller, R. G., Taivassalo, T., Davidson, M. M., Shanske, S., Bonilla, E., DiMauro, S.
|
|
<strong>Recurrent myoglobinuria due to a nonsense mutation in the COX I gene of mitochondrial DNA.</strong>
|
|
Neurology 55: 644-649, 2000.
|
|
|
|
|
|
[PubMed: 10980727]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.55.5.644]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lomax, M. I., Grossman, L. I.
|
|
<strong>Tissue-specific genes for respiratory proteins.</strong>
|
|
Trends Biochem. Sci. 14: 501-503, 1989. Note: Erratum: Trends Biochem. Sci. 15: 217 only, 1990.
|
|
|
|
|
|
[PubMed: 2560276]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0968-0004(89)90185-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lucioli, S., Hoffmeier, K., Carrozzo, R., Tessa, A., Ludwig, B., Santorelli, F. M.
|
|
<strong>Introducing a novel human mtDNA mutation into the Paracoccus denitrificans COX I gene explains functional deficits in a patient.</strong>
|
|
Neurogenetics 7: 51-57, 2006.
|
|
|
|
|
|
[PubMed: 16284789]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10048-005-0015-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montoya, J., Ojala, D., Attardi, G.
|
|
<strong>Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs.</strong>
|
|
Nature 290: 465-470, 1981.
|
|
|
|
|
|
[PubMed: 7219535]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/290465a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Namslauer, I., Brzezinski, P.
|
|
<strong>A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 3402-3407, 2009.
|
|
|
|
|
|
[PubMed: 19218458]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0811450106]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ojala, D., Montoya, J., Attardi, G.
|
|
<strong>tRNA punctuation model of RNA processing in human mitochondria.</strong>
|
|
Nature 290: 470-474, 1981.
|
|
|
|
|
|
[PubMed: 7219536]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/290470a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., McCarthy, J., Wallace, D. C.
|
|
<strong>Comparison of mitochondrially synthesized polypeptides of human, mouse, and monkey cell lines by a two-dimensional protease gel system.</strong>
|
|
Somat. Cell Molec. Genet. 10: 639-643, 1984.
|
|
|
|
|
|
[PubMed: 6438810]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01535230]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., Wallace, D. C.
|
|
<strong>Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction.</strong>
|
|
Molec. Cell. Biol. 2: 30-41, 1982.
|
|
|
|
|
|
[PubMed: 6955589]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/mcb.2.1.30-41.1982]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Palmer, G.
|
|
<strong>Current issues in the chemistry of cytochrome c oxidase.</strong>
|
|
J. Bioenerg. Biomembr. 25: 145-151, 1993.
|
|
|
|
|
|
[PubMed: 8389747]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00762856]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pandya, A., Xia, X.-J., Erdenetungalag, R., Amendola, M., Landa, B., Radnaabazar, J., Dangaasuren, B., Van Tuyle, G., Nance, W. E.
|
|
<strong>Heterozygous point mutations in the mitochondrial tRNA Ser(UCN) precursor coexisting with the A1555G mutation in deaf students from Mongolia. (Letter)</strong>
|
|
Am. J. Hum. Genet. 65: 1803-1806, 1999.
|
|
|
|
|
|
[PubMed: 10577941]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302658]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Parfait, B., Percheron, A., Chretien, D., Rustin, P., Munnich, A., Rotig, A.
|
|
<strong>No mitochondrial cytochrome oxidase (COX) gene mutations in 18 cases of COX deficiency.</strong>
|
|
Hum. Genet. 101: 247-250, 1997.
|
|
|
|
|
|
[PubMed: 9402980]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050625]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Polyak, K., Li, Y., Zhu, H., Lengauer, C., Willson, J. K. V., Markowitz, S. D., Trush, M. A., Kinzler, K. W., Vogelstein, B.
|
|
<strong>Somatic mutations of the mitochondrial genome in human colorectal tumours.</strong>
|
|
Nature Genet. 20: 291-293, 1998.
|
|
|
|
|
|
[PubMed: 9806551]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/3108]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Prochaska, L. J., Bisson, R., Capaldi, R. A., Steffens, G. C., Buse, G.
|
|
<strong>Inhibition of cytochrome c oxidase function by dicyclohexylcarbodiimide.</strong>
|
|
Biochim. Biophys. Acta 637: 360-373, 1981.
|
|
|
|
|
|
[PubMed: 6271198]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0005-2728(81)90175-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rousseau, D. L., Ching, Y., Wang, J.
|
|
<strong>Proton translocation in cytochrome c oxidase: redox linkage through proximal ligand exchange on cytochrome a3.</strong>
|
|
J. Bioenerg. Biomembr. 25: 165-176, 1993.
|
|
|
|
|
|
[PubMed: 8389749]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00762858]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shoffner, J. M., Wallace, D. C.
|
|
<strong>Oxidative phosphorylation diseases.In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic and Molecular Bases of Inherited Disease. Vol. 1. (7th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 1995. Pp. 1535-1609.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Temperley, R., Richter, R. Dennerlein, S., Lightowlers, R. N., Chrzanowska-Lightowlers, Z. M.
|
|
<strong>Hungry codons promote frameshifting in human mitochondrial ribosomes.</strong>
|
|
Science 327: 301 only, 2010.
|
|
|
|
|
|
[PubMed: 20075246]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1180674]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Varlamov, D. A., Kudin, A. P., Vielhaber, S., Schroder, R., Sassen, R., Becker, A., Kunz, D., Haug, K., Rebstock, J., Heils, A., Elger, C. E., Kunz, W. S.
|
|
<strong>Metabolic consequences of a novel missense mutation of the mtDNA CO I gene.</strong>
|
|
Hum. Molec. Genet. 11: 1797-1805, 2002.
|
|
|
|
|
|
[PubMed: 12140182]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/11.16.1797]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M.
|
|
<strong>Report of the committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong>
|
|
Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Stugard, C., Murdock, D., Schurr, T., Brown, M. D.
|
|
<strong>Ancient mtDNA sequences in the human nuclear genome: a potential source of errors in identifying pathogenic mutations.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 14900-14905, 1997.
|
|
|
|
|
|
[PubMed: 9405711]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.94.26.14900]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Yang, J., Ye, J., Lott, M. T., Oliver, N. A., McCarthy, J.
|
|
<strong>Computer prediction of peptide maps: assignment of polypeptides to human and mouse mitochondrial DNA genes by analysis of two dimensional-proteolytic digest gels.</strong>
|
|
Am. J. Hum. Genet. 38: 461-481, 1986.
|
|
|
|
|
|
[PubMed: 3518425]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. C.
|
|
<strong>Mitochondrial diseases: genotype versus phenotype.</strong>
|
|
Trends Genet. 9: 128-133, 1993.
|
|
|
|
|
|
[PubMed: 8516847]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0168-9525(93)90207-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Warburg, O.
|
|
<strong>On the origin of cancer cells.</strong>
|
|
Science 123: 309-314, 1956.
|
|
|
|
|
|
[PubMed: 13298683]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.123.3191.309]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wisloff, U., Najjar, S. M., Ellingsen, O., Haram, P. M., Swoap, S., Al-Share, Q., Fernstrom, M., Rezaei, K., Lee, S. J., Koch, L. G., Britton, S. L.
|
|
<strong>Cardiovascular risk factors emerge after artificial selection for low aerobic capacity.</strong>
|
|
Science 307: 418-420, 2005.
|
|
|
|
|
|
[PubMed: 15662013]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1108177]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yuan, H., Qian, Y., Xu, Y., Cao, J., Bai, L., Shen, W., Ji, F., Zhang, X., Kang, D., Mo, J. Q., Greinwald, J. H., Han, D., Zhai, S., Young, W.-Y., Guan, M.-X.
|
|
<strong>Cosegregation of the G7444A mutation in the mitochondrial COI/tRNA-Ser(UCN) genes with the 12S rRNA A1555G mutation in a Chinese family with aminoglycoside-induced and nonsyndromic hearing loss.</strong>
|
|
Am. J. Med. Genet. 138A: 133-140, 2005.
|
|
|
|
|
|
[PubMed: 16152638]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30952]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Bao Lige - updated : 10/14/2019<br>Ada Hamosh - updated : 2/1/2010<br>Marla J. F. O'Neill - updated : 10/5/2009<br>Ada Hamosh - updated : 3/26/2008<br>Cassandra L. Kniffin - updated : 5/17/2006<br>Cassandra L. Kniffin - updated : 10/25/2005<br>Ada Hamosh - updated : 2/2/2005<br>George E. Tiller - updated : 1/3/2005<br>George E. Tiller - updated : 7/2/2003<br>Majed J. Dasouki - updated : 1/30/2001<br>Victor A. McKusick - updated : 9/23/1999<br>Victor A. McKusick - updated : 6/15/1999<br>Michael J. Wright - updated : 2/12/1999<br>Victor A. McKusick - updated : 3/26/1998<br>Victor A. McKusick - updated : 2/6/1998<br>Victor A. McKusick - updated : 12/2/1997<br>Douglas C. Wallace - updated : 4/6/1994
|
|
</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 : 3/2/1993
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 03/11/2022<br>mgross : 10/14/2019<br>carol : 09/17/2018<br>carol : 07/08/2016<br>carol : 2/26/2013<br>mgross : 5/8/2012<br>carol : 5/24/2011<br>terry : 5/24/2011<br>wwang : 5/5/2010<br>ckniffin : 4/20/2010<br>carol : 3/3/2010<br>alopez : 2/2/2010<br>terry : 2/1/2010<br>carol : 1/19/2010<br>wwang : 10/14/2009<br>terry : 10/5/2009<br>ckniffin : 8/21/2009<br>alopez : 3/26/2008<br>wwang : 5/24/2006<br>ckniffin : 5/17/2006<br>wwang : 11/8/2005<br>ckniffin : 10/25/2005<br>alopez : 2/22/2005<br>alopez : 2/22/2005<br>terry : 2/2/2005<br>alopez : 1/3/2005<br>carol : 8/19/2003<br>carol : 7/10/2003<br>ckniffin : 7/8/2003<br>ckniffin : 7/7/2003<br>cwells : 7/2/2003<br>carol : 1/30/2001<br>mgross : 10/6/1999<br>terry : 9/23/1999<br>jlewis : 6/17/1999<br>terry : 6/15/1999<br>mgross : 3/4/1999<br>mgross : 3/1/1999<br>terry : 2/12/1999<br>dholmes : 5/11/1998<br>psherman : 3/26/1998<br>dholmes : 3/6/1998<br>mark : 2/15/1998<br>terry : 2/6/1998<br>mark : 12/9/1997<br>terry : 12/2/1997<br>mark : 6/23/1997<br>alopez : 6/18/1997<br>terry : 1/21/1997<br>mark : 4/9/1996<br>mark : 4/9/1996<br>mimman : 2/8/1996<br>mark : 6/19/1995<br>pfoster : 8/16/1994<br>mimadm : 4/26/1994<br>carol : 5/26/1993<br>carol : 5/17/1993
|
|
</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>
|
|
|
|
|