3851 lines
316 KiB
Text
3851 lines
316 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
|
|
|
|
- *604161 - KISS1 RECEPTOR; KISS1R
|
|
|
|
|
|
- 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=604161"><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">*604161</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/604161">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000116014;t=ENST00000234371" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=84634" 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=604161" 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=ENSG00000116014;t=ENST00000234371" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_032551,XM_047439545" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_032551" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=604161" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://hprd.org/summary?hprd_id=09167&isoform_id=09167_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.proteinatlas.org/search/KISS1R" 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/14041798,14330413,15077536,15626068,32454260,32454262,54033405,55164313,62865887,119589989,125987836,146327568,187954971,195969648,2217323491,2462568224" 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/Q969F8" 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=84634" 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=ENSG00000116014;t=ENST00000234371" 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=KISS1R" 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=KISS1R" 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+84634" 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/KISS1R" 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:84634" 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/84634" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr19&hgg_gene=ENST00000234371.10&hgg_start=917333&hgg_end=921005&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604161[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=604161[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000116014" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ebi.ac.uk/gwas/search?query=KISS1R" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.gwascentral.org/search?q=KISS1R" 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=KISS1R" 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=KISS1R&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/PA28899" 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:4510" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:2148793" 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/KISS1R#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:2148793" 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/84634/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=84634" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-060526-54" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:84634" 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=KISS1R&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
604161
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
KISS1 RECEPTOR; KISS1R
|
|
|
|
</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">
|
|
G PROTEIN-COUPLED RECEPTOR 54<br />
|
|
GPR54 METASTIN RECEPTOR
|
|
</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=KISS1R" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">KISS1R</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/19/35?start=-3&limit=10&highlight=35">19p13.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:917333-921005&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">19:917,333-921,005</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=176400,614837" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/19/35?start=-3&limit=10&highlight=35">
|
|
19p13.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Precocious puberty, central, 1
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/176400"> 176400 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hypogonadotropic hypogonadism 8 with or without anosmia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/614837"> 614837 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/604161" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/604161" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#8" class="mim-tip-reference" title="Lee, D. K., Nguyen, T., O'Neill, G. P., Cheng, R., Liu, Y., Howard, A. D., Coulombe, N., Tan, C. P., Tang-Nguyen, A.-T., George, S. R., O'Dowd, B. F. <strong>Discovery of a receptor related to the galanin receptors.</strong> FEBS Lett. 446: 103-107, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10100623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10100623</a>] [<a href="https://doi.org/10.1016/s0014-5793(99)00009-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10100623">Lee et al. (1999)</a> isolated rat brain cDNAs encoding a novel GPCR, which they designated Gpr54. The predicted protein shares 44 to 45% and 37% sequence identity in the transmembrane regions with the rat galanin receptors (see <a href="/entry/600377">600377</a>) and delta-1 opioid receptor (<a href="/entry/165195">165195</a>), respectively. Northern blot analysis and in situ hybridization indicated that rat Gpr54 has a complex and abundant central nervous system and peripheral tissue expression pattern. <a href="#8" class="mim-tip-reference" title="Lee, D. K., Nguyen, T., O'Neill, G. P., Cheng, R., Liu, Y., Howard, A. D., Coulombe, N., Tan, C. P., Tang-Nguyen, A.-T., George, S. R., O'Dowd, B. F. <strong>Discovery of a receptor related to the galanin receptors.</strong> FEBS Lett. 446: 103-107, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10100623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10100623</a>] [<a href="https://doi.org/10.1016/s0014-5793(99)00009-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10100623">Lee et al. (1999)</a> also identified the human GPR54 gene. The predicted 398-amino acid human protein is 81% identical to rat Gpr54. GPR54 is expressed in the human brain, pituitary gland, and placenta, as assessed by RT-PCR (<a href="#10" class="mim-tip-reference" title="Muir, A. I., Chamberlain, L., Elshourbagy, N. A., Michalovich, D., Moore, D. J., Calamari, A., Szekeres, P. G., Sarau, H. M., Chambers, J. K., Murdock, P., Steplewski, K., Shabon, U., and 10 others. <strong>AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1.</strong> J. Biol. Chem. 276: 28969-28975, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11387329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11387329</a>] [<a href="https://doi.org/10.1074/jbc.M102743200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11387329">Muir et al., 2001</a>; <a href="#7" class="mim-tip-reference" title="Kotani, M., Detheux, M., Vandenbogaerde, A., Communi, D., Vanderwinden, J.-M., Le Poul, E., Brezillon, S., Tyldesley, R., Suarez-Huerta, N., Vandeput, F., Blanpain, C., Schiffmann, S. N., Vassart, G., Parmentier, M. <strong>The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54.</strong> J. Biol. Chem. 276: 34631-34636, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11457843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11457843</a>] [<a href="https://doi.org/10.1074/jbc.M104847200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11457843">Kotani et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11457843+11387329+10100623" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Koemeter-Cox, A. I., Sherwood, T. W., Green, J. A., Steiner, R. A., Berbari, N. F., Yoder, B. K., Kauffman, A. S., Monsma, P. C., Brown, A., Askwith, C. C., Mykytyn, K. <strong>Primary cilia enhance kisspeptin receptor signaling on gonadotropin-releasing hormone neurons.</strong> Proc. Nat. Acad. Sci. 111: 10335-10340, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24982149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24982149</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24982149[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.1403286111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24982149">Koemeter-Cox et al. (2014)</a> found that Kiss1r was expressed on primary cilia of gonadotropin-releasing hormone (GNRH; see <a href="/entry/152760">152760</a>)-expressing neurons in mouse medial hypothalamus and basal forebrain. The number of neurons with multiple Kiss1r-positive cilia increased with sexual maturity in both male and female mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24982149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#8" class="mim-tip-reference" title="Lee, D. K., Nguyen, T., O'Neill, G. P., Cheng, R., Liu, Y., Howard, A. D., Coulombe, N., Tan, C. P., Tang-Nguyen, A.-T., George, S. R., O'Dowd, B. F. <strong>Discovery of a receptor related to the galanin receptors.</strong> FEBS Lett. 446: 103-107, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10100623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10100623</a>] [<a href="https://doi.org/10.1016/s0014-5793(99)00009-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10100623">Lee et al. (1999)</a> showed that the human GPR54 gene contains 5 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10100623" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By searching a sequence database, <a href="#8" class="mim-tip-reference" title="Lee, D. K., Nguyen, T., O'Neill, G. P., Cheng, R., Liu, Y., Howard, A. D., Coulombe, N., Tan, C. P., Tang-Nguyen, A.-T., George, S. R., O'Dowd, B. F. <strong>Discovery of a receptor related to the galanin receptors.</strong> FEBS Lett. 446: 103-107, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10100623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10100623</a>] [<a href="https://doi.org/10.1016/s0014-5793(99)00009-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10100623">Lee et al. (1999)</a> identified a human GPR54 ortholog within a contig (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AC005379" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AC005379</a>) from chromosome 19p13.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10100623" 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><a href="#12" class="mim-tip-reference" title="Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., Terao, Y., Kumano, S., Takatsu, Y., Masuda, Y., Ishibashi, Y., Watanabe, T., and 9 others. <strong>Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.</strong> Nature 411: 613-617, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11385580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11385580</a>] [<a href="https://doi.org/10.1038/35079135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11385580">Ohtaki et al. (2001)</a> isolated a carboxy-terminally amidated peptide of KISS1 (<a href="/entry/603286">603286</a>) from human placenta as the endogenous ligand of GPR54. They named the truncated form of KISS1 'metastin.' Metastin inhibits chemotaxis and invasion of GPR54-transfected CHO cells in vitro and attenuates pulmonary metastasis of GPR54-transfected B16-BL6 melanomas in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11385580" 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>KISS1 is a human metastasis suppressor gene whose product, metastin, had been identified as the endogenous agonist for GPR54, a Gq/11-coupled receptor (metastin receptor). <a href="#13" class="mim-tip-reference" title="Ringel, M. D., Hardy, E., Bernet, V. J., Burch, H. B., Schuppert, F., Burman, K. D., Saji, M. <strong>Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells.</strong> J. Clin. Endocr. Metab. 87: 2399-2402, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11994395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11994395</a>] [<a href="https://doi.org/10.1210/jcem.87.5.8626" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11994395">Ringel et al. (2002)</a> measured metastin and metastin receptor mRNA levels in 10 follicular carcinomas and 13 papillary carcinomas, 2 benign nonfunctioning follicular adenomas, and 11 normal thyroid samples, and evaluated the signaling pathways activated by metastin in ARO thyroid cancer cells that express the metastin receptor endogenously. Metastin receptor was not expressed in any normal thyroid or benign follicular adenoma samples, and was expressed in only a minority (2 of 10) of follicular carcinoma samples. However, the receptor was expressed in the majority (10 of 13) of papillary carcinomas. Increased levels of metastin receptor were detected in all 4 papillary carcinomas compared to adjacent normal tissue. Incubation of metastin receptor expressing ARO thyroid cancer cells with metastin resulted in activation of ERK, but not Akt. The authors concluded that metastin and/or metastin receptors have a potential role in modulating the biologic behavior of thyroid cancers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11994395" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using real-time PCR, <a href="#15" class="mim-tip-reference" title="Shahab, M., Mastronardi, C., Seminara, S. B., Crowley, W. F., Ojeda, S. R., Plant, T. M. <strong>Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.</strong> Proc. Nat. Acad. Sci. 102: 2129-2134, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15684075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15684075</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15684075[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.0409822102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15684075">Shahab et al. (2005)</a> found that the expression of Kiss1 mRNA increased with puberty in both male and female rhesus monkeys. Administration of kisspeptin-10 (112-121), a decapeptide derived from KISS1, to agonadal juvenile monkeys induced a GnRH response, as measured by a surge in plasma luteinizing hormone (LH; see <a href="/entry/152780">152780</a>). In intact females, but not in agonadal males, the level of Gpr54 mRNA in the hypothalamus increased about 3-fold from the juvenile to midpubertal stage. In situ hybridization detected robust Kiss1 and Gpr54 expression in the arcuate nucleus. <a href="#15" class="mim-tip-reference" title="Shahab, M., Mastronardi, C., Seminara, S. B., Crowley, W. F., Ojeda, S. R., Plant, T. M. <strong>Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.</strong> Proc. Nat. Acad. Sci. 102: 2129-2134, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15684075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15684075</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15684075[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.0409822102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15684075">Shahab et al. (2005)</a> concluded that KISS1 signaling through GPR54 in the primate hypothalamus at the end of the juvenile phase of development may contribute to the pubertal resurgence of pulsatile GnRH release. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15684075" 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="#11" class="mim-tip-reference" title="Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M. <strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong> Endocrinology 146: 156-163, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15375028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15375028</a>] [<a href="https://doi.org/10.1210/en.2004-0836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15375028">Navarro et al. (2005)</a> studied the effect of KISS1 peptide on LH secretion using in vitro and in vivo settings under different experimental conditions. Central intracerebroventricular administration of KISS1 peptide potently elicited LH secretion in vivo over a range of doses from 10 pmol to 1 nmol. The effect of centrally injected KISS1 appeared to be mediated via the hypothalamic LHRH (GNRH). However, no effect of central administration of KISS1 was detected on relative LHRH mRNA levels. Likewise, systemic (either intraperitoneal or intravascular) injection of KISS1 markedly stimulated LH secretion. <a href="#11" class="mim-tip-reference" title="Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M. <strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong> Endocrinology 146: 156-163, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15375028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15375028</a>] [<a href="https://doi.org/10.1210/en.2004-0836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15375028">Navarro et al. (2005)</a> found that LH-releasing activity of KISS1 was persistently observed after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e., relevant neurotransmitters in the neuroendocrine control of LH secretion. <a href="#11" class="mim-tip-reference" title="Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M. <strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong> Endocrinology 146: 156-163, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15375028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15375028</a>] [<a href="https://doi.org/10.1210/en.2004-0836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15375028">Navarro et al. (2005)</a> concluded that their results provided solid evidence for a potent stimulatory effect of KISS1 on LH release, acting at central levels (likely the hypothalamus) and eventually at the pituitary, and further documented a novel role of the KISS1/GPR54 system as a relevant downstream element in the neuroendocrine network governing LH secretion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15375028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 6 healthy male volunteers, <a href="#4" class="mim-tip-reference" title="Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., Bloom, S. R. <strong>Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.</strong> J. Clin. Endocr. Metab. 90: 6609-6615, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16174713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16174713</a>] [<a href="https://doi.org/10.1210/jc.2005-1468" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16174713">Dhillo et al. (2005)</a> found that elevation of plasma concentrations of kisspeptin significantly increased circulating LH, FSH (see <a href="/entry/136530">136530</a>), and testosterone levels. <a href="#4" class="mim-tip-reference" title="Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., Bloom, S. R. <strong>Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.</strong> J. Clin. Endocr. Metab. 90: 6609-6615, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16174713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16174713</a>] [<a href="https://doi.org/10.1210/jc.2005-1468" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16174713">Dhillo et al. (2005)</a> suggested that kisspeptin infusion may provide a novel mechanism for hypothalamic-pituitary-gonadal axis manipulation in disorders of the reproductive system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16174713" 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 patch-clamp recording of brain slices from adult mice, <a href="#6" class="mim-tip-reference" title="Koemeter-Cox, A. I., Sherwood, T. W., Green, J. A., Steiner, R. A., Berbari, N. F., Yoder, B. K., Kauffman, A. S., Monsma, P. C., Brown, A., Askwith, C. C., Mykytyn, K. <strong>Primary cilia enhance kisspeptin receptor signaling on gonadotropin-releasing hormone neurons.</strong> Proc. Nat. Acad. Sci. 111: 10335-10340, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24982149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24982149</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24982149[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.1403286111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24982149">Koemeter-Cox et al. (2014)</a> found that kisspeptin increased the firing rate of Gnrh neurons. Inhibition of ciliary outgrowth in Gnrh neurons attenuated kisspeptin-dependent firing of these neurons in male mice, but not in female mice. No other defects in sexual maturity or fertility were observed in the absence of Kiss1r-positive cilia on Gnrh neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24982149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Hypogonadotropic Hypogonadism 8 with or without Anosmia</em></strong></p><p>
|
|
Puberty, a complex biologic process involving sexual development, accelerated linear growth, and adrenal maturation, is initiated when gonadotropin-releasing hormone (see <a href="/entry/152760">152760</a> and <a href="/entry/602352">602352</a>) begins to be secreted by the hypothalamus. <a href="#14" class="mim-tip-reference" title="Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., Zahn, D., Dixon, J., Kaiser, U. B., Slaugenhaupt, S. A., Gusella, J. F., O'Rahilly, S., Carlton, M. B. L., Crowley, W. F., Jr., Aparicio, S. A. J. R., Colledge, W. H. <strong>The GPR54 gene as a regulator of puberty.</strong> New Eng. J. Med. 349: 1614-1627, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14573733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14573733</a>] [<a href="https://doi.org/10.1056/NEJMoa035322" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14573733">Seminara et al. (2003)</a> used complementary genetic approaches in studies in humans and mice to identify the genetic factors that determine the onset of puberty. In a consanguineous family with members who lacked pubertal development (idiopathic hypogonadotropic hypogonadism; see HH8, <a href="/entry/614837">614837</a>), they searched for mutations in the GPR54 gene. Functional differences between wildtype and mutant GPR54 were examined in vitro. In parallel, a Gpr54-deficient mouse model was created and phenotyped. <a href="#14" class="mim-tip-reference" title="Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., Zahn, D., Dixon, J., Kaiser, U. B., Slaugenhaupt, S. A., Gusella, J. F., O'Rahilly, S., Carlton, M. B. L., Crowley, W. F., Jr., Aparicio, S. A. J. R., Colledge, W. H. <strong>The GPR54 gene as a regulator of puberty.</strong> New Eng. J. Med. 349: 1614-1627, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14573733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14573733</a>] [<a href="https://doi.org/10.1056/NEJMoa035322" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14573733">Seminara et al. (2003)</a> found that affected patients in the index pedigree were homozygous for a leu148-to-ser mutation in the GPR54 gene (L148S; <a href="#0001">604161.0001</a>) and that an unrelated proband with idiopathic hypogonadotropic hypogonadism was a compound heterozygote for 2 mutations in the GPR54 gene (see <a href="#0002">604161.0002</a>). Gpr54-deficient mice had isolated hypogonadotropic hypogonadism (small testes in males and a delay in vaginal opening and an absence of follicular maturation in females), but they showed responsiveness to both exogenous gonadotropins and gonadotropin-releasing hormone and had normal levels of gonadotropin-releasing hormone in the hypothalamus. <a href="#14" class="mim-tip-reference" title="Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., Zahn, D., Dixon, J., Kaiser, U. B., Slaugenhaupt, S. A., Gusella, J. F., O'Rahilly, S., Carlton, M. B. L., Crowley, W. F., Jr., Aparicio, S. A. J. R., Colledge, W. H. <strong>The GPR54 gene as a regulator of puberty.</strong> New Eng. J. Med. 349: 1614-1627, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14573733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14573733</a>] [<a href="https://doi.org/10.1056/NEJMoa035322" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14573733">Seminara et al. (2003)</a> discussed possible mechanisms that would allow abnormalities of GPR54 to cause pubertal delay. They concluded that GPR54 is a key regulator of the biology of puberty. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14573733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., Milgrom, E. <strong>Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54.</strong> Proc. Nat. Acad. Sci. 100: 10972-10976, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12944565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12944565</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12944565[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.1834399100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12944565">De Roux et al. (2003)</a> studied a large consanguineous family in which 5 sibs had hypogonadotropic hypogonadism and a normal coding sequence of the gonadotropin-releasing hormone receptor gene (GNRHR; <a href="/entry/138850">138850</a>). By homozygosity whole-genome mapping, they identified a novel locus for hypogonadotropic hypogonadism on 19p13. Sequencing of several genes located within this region showed that all affected sibs in the family carried a homozygous 155-bp deletion in the GPR54 gene (<a href="#0004">604161.0004</a>). This deletion encompassed the splice acceptor site of the intron 4/exon 5 junction and part of exon 5. The deletion was absent or present on only 1 allele in unaffected family members. The study showed that loss of function of GPR54 is a cause of isolated hypogonadotropic hypogonadism and also identified GPR54, and possibly its ligand KISS1 (<a href="/entry/603286">603286</a>), as playing a major and previously unsuspected role in the physiology of the gonadotropic axis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12944565" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a male patient with anosmic hypogonadotropic hypogonadism, <a href="#9" class="mim-tip-reference" title="Miraoui, H., Dwyer, A. A., Sykiotis, G. P., Plummer, L., Chung, W., Feng, B., Beenken, A., Clarke, J., Pers, T. H., Dworzynski, P., Keefe, K., Niedziela, M., and 17 others. <strong>Mutations in FGF17, IL17RD, DUPS6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.</strong> Am. J. Hum. Genet. 92: 725-743, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23643382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23643382</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23643382[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.04.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23643382">Miraoui et al. (2013)</a> identified 2 heterozygous missense mutations, 1 in the KISS1R gene (A194D; <a href="#0007">604161.0007</a>) and 1 in the IL17RD gene (A735P; <a href="/entry/606807#0003">606807.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23643382" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 2 unrelated families with normosmic hypogonadotropic hypogonadism, <a href="#2" class="mim-tip-reference" title="Brioude, F., Bouligand, J., Francou, B., Fagart, J., Roussel, R., Viengchareun, S., Combettes, L., Brailly-Tabard, S., Lombes, M., Young, J., Guiochon-Mantel, A. <strong>Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor): clinical evaluation and molecular characterization of a novel mutation.</strong> PLoS One 8: e53896, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23349759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23349759</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23349759[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/10.1371/journal.pone.0053896" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23349759">Brioude et al. (2013)</a> analyzed 9 HH-associated genes and identified mutations in the KISS1R gene in both families (<a href="#0003">604161.0003</a>, <a href="#0005">604161.0005</a>, and <a href="#0008">604161.0008</a>). The authors noted that the observed pituitary and gonadal response to pulsatile GNRH administration in these patients supported the hypothesis that disruption of the gonadotropic axis due to KISS1R loss of function occurs exclusively in the hypothalamus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23349759" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Central Precocious Puberty 1</em></strong></p><p>
|
|
Gonadotropin-dependent, or central, precocious puberty (see <a href="/entry/176400">176400</a>) is caused by early maturation of the hypothalamic-pituitary-gonadal axis. <a href="#16" class="mim-tip-reference" title="Teles, M. G., Bianco, S. D. C., Brito, V. N., Trarbach, E. B., Kuohung, W., Xu, S., Seminara, S. B., Mendonca, B. B., Kaiser, U. B., Latronico, A. C. <strong>A GPR54-activating mutation in a patient with central precocious puberty.</strong> New Eng. J. Med. 358: 709-715, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18272894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18272894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18272894[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa073443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18272894">Teles et al. (2008)</a> identified an autosomal dominant GPR54 mutation (R386P; <a href="#0006">604161.0006</a>) in an adopted girl with idiopathic central precocious puberty. In vitro studies showed that this mutation led to prolonged activation of intracellular signaling pathways in response to kisspeptin, the ligand of GPR54. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18272894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#5" class="mim-tip-reference" title="Gaytan, F., Garcia-Galiano, D., Dorfman, M. D., Manfredi-Lozano, M., Castellano, J. M., Dissen, G. A., Ojeda, S. R., Tena-Sempere, M. <strong>Kisspeptin receptor haplo-insufficiency causes premature ovarian failure despite preserved gonadotropin secretion.</strong> Endocrinology 155: 3088-3097, 2014. Note: Erratum: Endocrinology 156: 3402, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24885574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24885574</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24885574[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/10.1210/en.2014-1110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24885574">Gaytan et al. (2014)</a> studied Kiss1r-haploinsufficient and -null mice. Kiss1r hypomorphic mice displayed a premature decline in ovulatory rate, followed by progressive loss of antral follicles, oocyte loss, and a reduction in all categories of preantral follicles; these alterations were accompanied by reduced fertility. Mice over 48 weeks of age showed atrophic ovaries that lacked growing follicles and corpora lutea. This was associated with a drop in ovarian Kiss1r mRNA expression, but without a decrease in circulating gonadotropins: rather, FSH levels increased in aged hypomorphic mice, reflecting loss of follicular function. Kiss1r-null mice, which did not spontaneously ovulate and had arrested follicle development, failed to show normal ovulatory responses to standard gonadotropin priming and required GnRH prestimulation for 1 week to achieve gonadotropin-induced ovulation. However, the magnitude of ovulatory responses was only half of that seen in immature wildtype control mice. <a href="#5" class="mim-tip-reference" title="Gaytan, F., Garcia-Galiano, D., Dorfman, M. D., Manfredi-Lozano, M., Castellano, J. M., Dissen, G. A., Ojeda, S. R., Tena-Sempere, M. <strong>Kisspeptin receptor haplo-insufficiency causes premature ovarian failure despite preserved gonadotropin secretion.</strong> Endocrinology 155: 3088-3097, 2014. Note: Erratum: Endocrinology 156: 3402, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24885574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24885574</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24885574[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/10.1210/en.2014-1110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24885574">Gaytan et al. (2014)</a> concluded that KISS1R haploinsufficiency induces a state of premature ovarian failure (see POF1, <a href="/entry/311360">311360</a>) that is not attributable to defective gonadotropin secretion and cannot be fully rescued by gonadotropin replacement, suggesting a direct ovarian role for kisspeptin signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24885574" 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>8 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/604161" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=604161[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 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KISS1R, LEU148SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28939719 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939719;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28939719?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28939719" 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=rs28939719" 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=RCV000030878" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030878" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030878</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#1" class="mim-tip-reference" title="Bo-Abbas, Y., Acierno, J. S., Jr., Shagoury, J. K., Crowley, W. F., Jr., Seminara, S. B. <strong>Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes.</strong> J. Clin. Endocr. Metab. 88: 2730-2737, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12788881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12788881</a>] [<a href="https://doi.org/10.1210/jc.2002-021948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12788881">Bo-Abbas et al. (2003)</a> described a large Saudi Arabian family in which 2 brothers and a sister in 1 sibship married 2 sisters and a brother in a first-cousin sibship. The family sought medical attention for infertility. Six of the 19 offspring in the 3 sibships (4 men and 2 women), at least 1 from each mating, met the standard diagnostic criteria for idiopathic hypogonadotropic hypogonadism (HH8; <a href="/entry/614837">614837</a>) (inappropriately low gonadotropin concentrations in the presence of prepubertal concentrations of sex steroids, normal anterior pituitary function, and normal findings on imaging of the brain) and had responsiveness to exogenous, pulsatile, gonadotropin-releasing hormone (see <a href="/entry/152760">152760</a> and <a href="/entry/602352">602352</a>). In all 6 affected members, <a href="#14" class="mim-tip-reference" title="Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., Zahn, D., Dixon, J., Kaiser, U. B., Slaugenhaupt, S. A., Gusella, J. F., O'Rahilly, S., Carlton, M. B. L., Crowley, W. F., Jr., Aparicio, S. A. J. R., Colledge, W. H. <strong>The GPR54 gene as a regulator of puberty.</strong> New Eng. J. Med. 349: 1614-1627, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14573733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14573733</a>] [<a href="https://doi.org/10.1056/NEJMoa035322" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14573733">Seminara et al. (2003)</a> identified a 443T-C transition in exon 3 of the GPR54 gene, resulting in a leu148-to-ser (L148S) substitution in the second intracellular loop. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14573733+12788881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In HEK293 cells, <a href="#18" class="mim-tip-reference" title="Wacker, J. L., Feller, D. B., Tang, X.-B., DeFino, M. C., Namkung, Y., Lyssand, J. S., Mhyre, A. J., Tan, X., Jensen, J. B., Hague, C. <strong>Disease-causing mutation in GPR54 reveals the importance of the second intracellular loop for class A G-protein-coupled receptor function.</strong> J. Biol. Chem. 283: 31068-31078, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18772143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18772143</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18772143[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M805251200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18772143">Wacker et al. (2008)</a> performed biochemical, immunocytochemical, and pharmacologic analysis of the L148S mutation, located at a highly conserved residue in the second intracellular loop of GPR54. They found that L148S mutation did not affect the expression, ligand-binding properties, or protein interaction network of GPR54. In contrast, diverse GPR54 functional responses were markedly inhibited by the L148S mutation, with the mutant receptor neither initiating G-protein dissociation nor activating phospholipase C (see <a href="/entry/172420">172420</a>) or ERK1/2 (see <a href="/entry/176948">176948</a>). Fluorescence resonance energy transfer analysis strongly suggested that the L148S mutation impaired the ligand-induced catalytic activity of G-alpha. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18772143" 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 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KISS1R, ARG331TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894701 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894701;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=rs104894701" 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=rs104894701" 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=RCV000030879" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030879" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030879</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#14" class="mim-tip-reference" title="Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., Zahn, D., Dixon, J., Kaiser, U. B., Slaugenhaupt, S. A., Gusella, J. F., O'Rahilly, S., Carlton, M. B. L., Crowley, W. F., Jr., Aparicio, S. A. J. R., Colledge, W. H. <strong>The GPR54 gene as a regulator of puberty.</strong> New Eng. J. Med. 349: 1614-1627, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14573733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14573733</a>] [<a href="https://doi.org/10.1056/NEJMoa035322" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14573733">Seminara et al. (2003)</a> studied 63 unrelated patients with normosmic idiopathic hypogonadotropic hypogonadism and 20 patients with anosmic hypogonadotropic hypogonadism. In 1 patient, a black man with idiopathic hypogonadotropic hypogonadism (HH8; <a href="/entry/614837">614837</a>), they identified compound heterozygosity for a 991C-T transition in exon 5 of the GPR54 gene, causing replacement of an arginine at residue 331 with a premature stop codon (R331X), and a 1195T-A transversion in exon 5, which replaced the stop codon at residue 399 with an arginine (X399R; <a href="#0003">604161.0003</a>). This nonstop mutation resulted in the continuation of the open reading frame to the poly(A) signal, with no intervening stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14573733" 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 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KISS1R, TER399ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894702 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894702;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894702?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894702" 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=rs104894702" 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=RCV000030880 OR RCV001851690 OR RCV003944803 OR RCV004782009" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030880, RCV001851690, RCV003944803, RCV004782009" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030880...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the ter399-to-arg (X399R) mutation in the KISS1R gene that was found in compound heterozygous state in a patient with idiopathic hypogonadotropic hypogonadism (HH8; <a href="/entry/614837">614837</a>) by <a href="#14" class="mim-tip-reference" title="Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., Zahn, D., Dixon, J., Kaiser, U. B., Slaugenhaupt, S. A., Gusella, J. F., O'Rahilly, S., Carlton, M. B. L., Crowley, W. F., Jr., Aparicio, S. A. J. R., Colledge, W. H. <strong>The GPR54 gene as a regulator of puberty.</strong> New Eng. J. Med. 349: 1614-1627, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14573733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14573733</a>] [<a href="https://doi.org/10.1056/NEJMoa035322" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14573733">Seminara et al. (2003)</a>, see <a href="#0002">604161.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14573733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a French Caucasian man with normosmic hypogonadotropic hypogonadism, <a href="#2" class="mim-tip-reference" title="Brioude, F., Bouligand, J., Francou, B., Fagart, J., Roussel, R., Viengchareun, S., Combettes, L., Brailly-Tabard, S., Lombes, M., Young, J., Guiochon-Mantel, A. <strong>Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor): clinical evaluation and molecular characterization of a novel mutation.</strong> PLoS One 8: e53896, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23349759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23349759</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23349759[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/10.1371/journal.pone.0053896" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23349759">Brioude et al. (2013)</a> identified compound heterozygosity for the X399R and L102P (<a href="#0005">604161.0005</a>) substitutions in the KISS1R gene. His unaffected mother was heterozygous for the L102P mutation; neither mutation was found in 200 eugonadal Caucasian individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23349759" 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 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KISS1R, 155-BP DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000030881" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030881" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030881</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By homozygosity mapping, <a href="#3" class="mim-tip-reference" title="de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., Milgrom, E. <strong>Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54.</strong> Proc. Nat. Acad. Sci. 100: 10972-10976, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12944565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12944565</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12944565[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.1834399100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12944565">de Roux et al. (2003)</a> found that a locus on 19p13 was involved in hypogonadotropic hypogonadism (HH8; <a href="/entry/614837">614837</a>) in affected members of a sibship whose parents were first cousins. Sequencing of several genes localized within this region showed that all affected sibs carried a homozygous 155-bp deletion in the GPR54 gene encompassing the splice acceptor site of the intron 4/exon 5 junction and part of exon 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12944565" 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 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KISS1R, LEU102PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894703 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894703;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894703?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894703" 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=rs104894703" 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=RCV000030882 OR RCV001197427 OR RCV001311147 OR RCV003989280" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030882, RCV001197427, RCV001311147, RCV003989280" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030882...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 patients with isolated hypogonadotropic hypogonadism (HH8; <a href="/entry/614837">614837</a>) from 2 unrelated Arab Muslim families from Syria and Israel, <a href="#17" class="mim-tip-reference" title="Tenenbaum-Rakover, Y., Commenges-Ducos, M., Iovane, A., Aumas, C., Admoni, O., de Roux, N. <strong>Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54.</strong> J. Clin. Endocr. Metab. 92: 1137-1144, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17164310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17164310</a>] [<a href="https://doi.org/10.1210/jc.2006-2147" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17164310">Tenenbaum-Rakover et al. (2007)</a> identified homozygosity for a 305T-C transition in the GPR54 gene, leading to a leu102-to-pro (L102P) substitution, which completely inhibited GPR54 signaling. Phenotypic analysis revealed variable expressivity in the same family, either partial or complete gonadotropic deficiency. LH pulsatility analysis showed peaks with normal frequency but low amplitude. Repeated GnRH tests performed between 12 and 21 years of age in 1 affected male revealed progressive changes in pituitary response from an early pubertal to an almost full pubertal pattern. <a href="#17" class="mim-tip-reference" title="Tenenbaum-Rakover, Y., Commenges-Ducos, M., Iovane, A., Aumas, C., Admoni, O., de Roux, N. <strong>Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54.</strong> J. Clin. Endocr. Metab. 92: 1137-1144, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17164310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17164310</a>] [<a href="https://doi.org/10.1210/jc.2006-2147" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17164310">Tenenbaum-Rakover et al. (2007)</a> concluded that GPR54 inactivation does not impede neuroendocrine onset of puberty; rather, it delays and slows down pubertal maturation of the gonadotropic axis. The L102P loss of function mutation in GPR54 results in a more quantitative than qualitative defect of gonadotropic axis activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17164310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For discussion of the L102P mutation in the KISS1R gene that was found in compound heterozygous state in a patient with HH8 by <a href="#2" class="mim-tip-reference" title="Brioude, F., Bouligand, J., Francou, B., Fagart, J., Roussel, R., Viengchareun, S., Combettes, L., Brailly-Tabard, S., Lombes, M., Young, J., Guiochon-Mantel, A. <strong>Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor): clinical evaluation and molecular characterization of a novel mutation.</strong> PLoS One 8: e53896, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23349759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23349759</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23349759[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/10.1371/journal.pone.0053896" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23349759">Brioude et al. (2013)</a>, see <a href="#0003">604161.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23349759" 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 PRECOCIOUS PUBERTY, CENTRAL, 1 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KISS1R, ARG386PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908499 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908499;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121908499?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908499" 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=rs121908499" 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=RCV000006116 OR RCV000489218 OR RCV004820818" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006116, RCV000489218, RCV004820818" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006116...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#16" class="mim-tip-reference" title="Teles, M. G., Bianco, S. D. C., Brito, V. N., Trarbach, E. B., Kuohung, W., Xu, S., Seminara, S. B., Mendonca, B. B., Kaiser, U. B., Latronico, A. C. <strong>A GPR54-activating mutation in a patient with central precocious puberty.</strong> New Eng. J. Med. 358: 709-715, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18272894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18272894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18272894[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa073443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18272894">Teles et al. (2008)</a> identified a heterozygous arg386-to-pro (R386P) activating mutation in the GPR54 gene in an adopted girl with idiopathic central precocious puberty (CPPB1; <a href="/entry/176400">176400</a>). Functional studies indicated that the mutation prolonged intracellular GPR54 signaling in response to kisspeptin (<a href="/entry/603286">603286</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18272894" 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 HYPOGONADOTROPIC HYPOGONADISM 8 WITH ANOSMIA, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KISS1R, ALA194ASP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs397514699 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514699;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs397514699?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397514699" 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=rs397514699" 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=RCV000043601 OR RCV002514181" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000043601, RCV002514181" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000043601...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient with congenital hypogonadotropic hypogonadism with anosmia (HH8; <a href="/entry/614837">614837</a>), who also had hearing loss, <a href="#9" class="mim-tip-reference" title="Miraoui, H., Dwyer, A. A., Sykiotis, G. P., Plummer, L., Chung, W., Feng, B., Beenken, A., Clarke, J., Pers, T. H., Dworzynski, P., Keefe, K., Niedziela, M., and 17 others. <strong>Mutations in FGF17, IL17RD, DUPS6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.</strong> Am. J. Hum. Genet. 92: 725-743, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23643382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23643382</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23643382[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.04.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23643382">Miraoui et al. (2013)</a> identified heterozygosity for a c.581C-A transversion in the KISS1R gene, resulting in an ala194-to-asp (A194D) substitution. The patient was also heterozygous for a missense mutation in the IL17RD gene (A735V; <a href="/entry/606807#0003">606807.0003</a>). The patient had a sister who had hypogonadotropic hypogonadism with anosmia, and their parents were unaffected; family member genotypes were unavailable. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23643382" 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 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
KISS1R, TYR313HIS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs587777844 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777844;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs587777844?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs587777844" 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=rs587777844" 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=RCV000144561" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144561" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144561</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a brother and 2 sisters from a consanguineous Portuguese family with normosmic hypogonadotropic hypogonadism (HH8; <a href="/entry/614837">614837</a>), <a href="#2" class="mim-tip-reference" title="Brioude, F., Bouligand, J., Francou, B., Fagart, J., Roussel, R., Viengchareun, S., Combettes, L., Brailly-Tabard, S., Lombes, M., Young, J., Guiochon-Mantel, A. <strong>Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor): clinical evaluation and molecular characterization of a novel mutation.</strong> PLoS One 8: e53896, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23349759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23349759</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23349759[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/10.1371/journal.pone.0053896" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23349759">Brioude et al. (2013)</a> identified homozygosity for a c.937T-C transition in the KISS1R gene, resulting in a tyr313-to-his (Y313H) substitution at a highly conserved residue in the seventh transmembrane domain. Their unaffected parents were heterozygous for the mutation, which was not found in 200 chromosomes from eugonadal Caucasian individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23349759" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Bo-Abbas2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bo-Abbas, Y., Acierno, J. S., Jr., Shagoury, J. K., Crowley, W. F., Jr., Seminara, S. B.
|
|
<strong>Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes.</strong>
|
|
J. Clin. Endocr. Metab. 88: 2730-2737, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12788881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12788881</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12788881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2002-021948" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Brioude2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brioude, F., Bouligand, J., Francou, B., Fagart, J., Roussel, R., Viengchareun, S., Combettes, L., Brailly-Tabard, S., Lombes, M., Young, J., Guiochon-Mantel, A.
|
|
<strong>Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor): clinical evaluation and molecular characterization of a novel mutation.</strong>
|
|
PLoS One 8: e53896, 2013. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23349759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23349759</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23349759[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=23349759" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1371/journal.pone.0053896" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="de Roux2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., Milgrom, E.
|
|
<strong>Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 10972-10976, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12944565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12944565</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12944565[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=12944565" 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.1834399100" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Dhillo2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., Bloom, S. R.
|
|
<strong>Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.</strong>
|
|
J. Clin. Endocr. Metab. 90: 6609-6615, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16174713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16174713</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16174713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2005-1468" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Gaytan2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gaytan, F., Garcia-Galiano, D., Dorfman, M. D., Manfredi-Lozano, M., Castellano, J. M., Dissen, G. A., Ojeda, S. R., Tena-Sempere, M.
|
|
<strong>Kisspeptin receptor haplo-insufficiency causes premature ovarian failure despite preserved gonadotropin secretion.</strong>
|
|
Endocrinology 155: 3088-3097, 2014. Note: Erratum: Endocrinology 156: 3402, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24885574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24885574</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24885574[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=24885574" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/en.2014-1110" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Koemeter-Cox2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koemeter-Cox, A. I., Sherwood, T. W., Green, J. A., Steiner, R. A., Berbari, N. F., Yoder, B. K., Kauffman, A. S., Monsma, P. C., Brown, A., Askwith, C. C., Mykytyn, K.
|
|
<strong>Primary cilia enhance kisspeptin receptor signaling on gonadotropin-releasing hormone neurons.</strong>
|
|
Proc. Nat. Acad. Sci. 111: 10335-10340, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24982149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24982149</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24982149[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=24982149" 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.1403286111" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Kotani2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kotani, M., Detheux, M., Vandenbogaerde, A., Communi, D., Vanderwinden, J.-M., Le Poul, E., Brezillon, S., Tyldesley, R., Suarez-Huerta, N., Vandeput, F., Blanpain, C., Schiffmann, S. N., Vassart, G., Parmentier, M.
|
|
<strong>The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54.</strong>
|
|
J. Biol. Chem. 276: 34631-34636, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11457843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11457843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11457843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M104847200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Lee1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, D. K., Nguyen, T., O'Neill, G. P., Cheng, R., Liu, Y., Howard, A. D., Coulombe, N., Tan, C. P., Tang-Nguyen, A.-T., George, S. R., O'Dowd, B. F.
|
|
<strong>Discovery of a receptor related to the galanin receptors.</strong>
|
|
FEBS Lett. 446: 103-107, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10100623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10100623</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10100623" 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/s0014-5793(99)00009-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Miraoui2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Miraoui, H., Dwyer, A. A., Sykiotis, G. P., Plummer, L., Chung, W., Feng, B., Beenken, A., Clarke, J., Pers, T. H., Dworzynski, P., Keefe, K., Niedziela, M., and 17 others.
|
|
<strong>Mutations in FGF17, IL17RD, DUPS6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.</strong>
|
|
Am. J. Hum. Genet. 92: 725-743, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23643382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23643382</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23643382[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=23643382" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2013.04.008" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Muir2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muir, A. I., Chamberlain, L., Elshourbagy, N. A., Michalovich, D., Moore, D. J., Calamari, A., Szekeres, P. G., Sarau, H. M., Chambers, J. K., Murdock, P., Steplewski, K., Shabon, U., and 10 others.
|
|
<strong>AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1.</strong>
|
|
J. Biol. Chem. 276: 28969-28975, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11387329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11387329</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11387329" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M102743200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Navarro2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M.
|
|
<strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong>
|
|
Endocrinology 146: 156-163, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15375028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15375028</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15375028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/en.2004-0836" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Ohtaki2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., Terao, Y., Kumano, S., Takatsu, Y., Masuda, Y., Ishibashi, Y., Watanabe, T., and 9 others.
|
|
<strong>Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.</strong>
|
|
Nature 411: 613-617, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11385580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11385580</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11385580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/35079135" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Ringel2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ringel, M. D., Hardy, E., Bernet, V. J., Burch, H. B., Schuppert, F., Burman, K. D., Saji, M.
|
|
<strong>Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells.</strong>
|
|
J. Clin. Endocr. Metab. 87: 2399-2402, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11994395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11994395</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11994395" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.87.5.8626" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Seminara2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., Zahn, D., Dixon, J., Kaiser, U. B., Slaugenhaupt, S. A., Gusella, J. F., O'Rahilly, S., Carlton, M. B. L., Crowley, W. F., Jr., Aparicio, S. A. J. R., Colledge, W. H.
|
|
<strong>The GPR54 gene as a regulator of puberty.</strong>
|
|
New Eng. J. Med. 349: 1614-1627, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14573733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14573733</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14573733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa035322" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Shahab2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shahab, M., Mastronardi, C., Seminara, S. B., Crowley, W. F., Ojeda, S. R., Plant, T. M.
|
|
<strong>Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 2129-2134, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15684075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15684075</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15684075[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=15684075" 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.0409822102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Teles2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Teles, M. G., Bianco, S. D. C., Brito, V. N., Trarbach, E. B., Kuohung, W., Xu, S., Seminara, S. B., Mendonca, B. B., Kaiser, U. B., Latronico, A. C.
|
|
<strong>A GPR54-activating mutation in a patient with central precocious puberty.</strong>
|
|
New Eng. J. Med. 358: 709-715, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18272894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18272894</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18272894[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=18272894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa073443" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Tenenbaum-Rakover2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tenenbaum-Rakover, Y., Commenges-Ducos, M., Iovane, A., Aumas, C., Admoni, O., de Roux, N.
|
|
<strong>Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54.</strong>
|
|
J. Clin. Endocr. Metab. 92: 1137-1144, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17164310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17164310</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17164310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2006-2147" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Wacker2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wacker, J. L., Feller, D. B., Tang, X.-B., DeFino, M. C., Namkung, Y., Lyssand, J. S., Mhyre, A. J., Tan, X., Jensen, J. B., Hague, C.
|
|
<strong>Disease-causing mutation in GPR54 reveals the importance of the second intracellular loop for class A G-protein-coupled receptor function.</strong>
|
|
J. Biol. Chem. 283: 31068-31078, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18772143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18772143</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18772143[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=18772143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M805251200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 11/3/2014
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Patricia A. Hartz - updated : 10/29/2014<br>Marla J. F. O'Neill - updated : 10/10/2014<br>Marla J. F. O'Neill - updated : 6/5/2013<br>Marla J. F. O'Neill - updated : 3/10/2009<br>Victor A. McKusick - updated : 3/19/2008<br>John A. Phillips, III - updated : 1/8/2008<br>John A. Phillips, III - updated : 3/19/2007<br>Ada Hamosh - updated : 11/28/2006<br>Patricia A. Hartz - updated : 6/8/2005<br>Victor A. McKusick - updated : 12/8/2003<br>Victor A. McKusick - updated : 11/3/2003<br>John A. Phillips, III - updated : 10/16/2002
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Rebekah S. Rasooly : 9/7/1999
|
|
</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 : 08/11/2016
|
|
</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">
|
|
mcolton : 06/24/2015<br>carol : 11/6/2014<br>mcolton : 11/3/2014<br>mgross : 10/30/2014<br>mcolton : 10/29/2014<br>carol : 10/24/2014<br>carol : 10/15/2014<br>mcolton : 10/10/2014<br>carol : 7/30/2013<br>carol : 7/29/2013<br>alopez : 6/5/2013<br>carol : 9/27/2012<br>joanna : 3/23/2009<br>wwang : 3/16/2009<br>wwang : 3/16/2009<br>terry : 3/10/2009<br>alopez : 3/25/2008<br>terry : 3/19/2008<br>carol : 1/8/2008<br>terry : 1/8/2008<br>carol : 3/19/2007<br>alopez : 12/7/2006<br>terry : 11/28/2006<br>wwang : 6/17/2005<br>wwang : 6/9/2005<br>terry : 6/8/2005<br>tkritzer : 12/17/2003<br>tkritzer : 12/10/2003<br>terry : 12/8/2003<br>tkritzer : 11/6/2003<br>terry : 11/3/2003<br>alopez : 10/16/2002<br>alopez : 6/15/2001<br>alopez : 6/15/2001<br>terry : 6/14/2001<br>alopez : 9/7/1999
|
|
</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> 604161
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
KISS1 RECEPTOR; KISS1R
|
|
|
|
</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">
|
|
G PROTEIN-COUPLED RECEPTOR 54<br />
|
|
GPR54 METASTIN RECEPTOR
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: KISS1R</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 19p13.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 19:917,333-921,005 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
19p13.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Precocious puberty, central, 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
176400
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hypogonadotropic hypogonadism 8 with or without anosmia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614837
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Lee et al. (1999) isolated rat brain cDNAs encoding a novel GPCR, which they designated Gpr54. The predicted protein shares 44 to 45% and 37% sequence identity in the transmembrane regions with the rat galanin receptors (see 600377) and delta-1 opioid receptor (165195), respectively. Northern blot analysis and in situ hybridization indicated that rat Gpr54 has a complex and abundant central nervous system and peripheral tissue expression pattern. Lee et al. (1999) also identified the human GPR54 gene. The predicted 398-amino acid human protein is 81% identical to rat Gpr54. GPR54 is expressed in the human brain, pituitary gland, and placenta, as assessed by RT-PCR (Muir et al., 2001; Kotani et al., 2001). </p><p>Koemeter-Cox et al. (2014) found that Kiss1r was expressed on primary cilia of gonadotropin-releasing hormone (GNRH; see 152760)-expressing neurons in mouse medial hypothalamus and basal forebrain. The number of neurons with multiple Kiss1r-positive cilia increased with sexual maturity in both male and female mice. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Lee et al. (1999) showed that the human GPR54 gene contains 5 exons. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By searching a sequence database, Lee et al. (1999) identified a human GPR54 ortholog within a contig (GenBank AC005379) from chromosome 19p13.3. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ohtaki et al. (2001) isolated a carboxy-terminally amidated peptide of KISS1 (603286) from human placenta as the endogenous ligand of GPR54. They named the truncated form of KISS1 'metastin.' Metastin inhibits chemotaxis and invasion of GPR54-transfected CHO cells in vitro and attenuates pulmonary metastasis of GPR54-transfected B16-BL6 melanomas in vivo. </p><p>KISS1 is a human metastasis suppressor gene whose product, metastin, had been identified as the endogenous agonist for GPR54, a Gq/11-coupled receptor (metastin receptor). Ringel et al. (2002) measured metastin and metastin receptor mRNA levels in 10 follicular carcinomas and 13 papillary carcinomas, 2 benign nonfunctioning follicular adenomas, and 11 normal thyroid samples, and evaluated the signaling pathways activated by metastin in ARO thyroid cancer cells that express the metastin receptor endogenously. Metastin receptor was not expressed in any normal thyroid or benign follicular adenoma samples, and was expressed in only a minority (2 of 10) of follicular carcinoma samples. However, the receptor was expressed in the majority (10 of 13) of papillary carcinomas. Increased levels of metastin receptor were detected in all 4 papillary carcinomas compared to adjacent normal tissue. Incubation of metastin receptor expressing ARO thyroid cancer cells with metastin resulted in activation of ERK, but not Akt. The authors concluded that metastin and/or metastin receptors have a potential role in modulating the biologic behavior of thyroid cancers. </p><p>Using real-time PCR, Shahab et al. (2005) found that the expression of Kiss1 mRNA increased with puberty in both male and female rhesus monkeys. Administration of kisspeptin-10 (112-121), a decapeptide derived from KISS1, to agonadal juvenile monkeys induced a GnRH response, as measured by a surge in plasma luteinizing hormone (LH; see 152780). In intact females, but not in agonadal males, the level of Gpr54 mRNA in the hypothalamus increased about 3-fold from the juvenile to midpubertal stage. In situ hybridization detected robust Kiss1 and Gpr54 expression in the arcuate nucleus. Shahab et al. (2005) concluded that KISS1 signaling through GPR54 in the primate hypothalamus at the end of the juvenile phase of development may contribute to the pubertal resurgence of pulsatile GnRH release. </p><p>Navarro et al. (2005) studied the effect of KISS1 peptide on LH secretion using in vitro and in vivo settings under different experimental conditions. Central intracerebroventricular administration of KISS1 peptide potently elicited LH secretion in vivo over a range of doses from 10 pmol to 1 nmol. The effect of centrally injected KISS1 appeared to be mediated via the hypothalamic LHRH (GNRH). However, no effect of central administration of KISS1 was detected on relative LHRH mRNA levels. Likewise, systemic (either intraperitoneal or intravascular) injection of KISS1 markedly stimulated LH secretion. Navarro et al. (2005) found that LH-releasing activity of KISS1 was persistently observed after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e., relevant neurotransmitters in the neuroendocrine control of LH secretion. Navarro et al. (2005) concluded that their results provided solid evidence for a potent stimulatory effect of KISS1 on LH release, acting at central levels (likely the hypothalamus) and eventually at the pituitary, and further documented a novel role of the KISS1/GPR54 system as a relevant downstream element in the neuroendocrine network governing LH secretion. </p><p>In a study of 6 healthy male volunteers, Dhillo et al. (2005) found that elevation of plasma concentrations of kisspeptin significantly increased circulating LH, FSH (see 136530), and testosterone levels. Dhillo et al. (2005) suggested that kisspeptin infusion may provide a novel mechanism for hypothalamic-pituitary-gonadal axis manipulation in disorders of the reproductive system. </p><p>By patch-clamp recording of brain slices from adult mice, Koemeter-Cox et al. (2014) found that kisspeptin increased the firing rate of Gnrh neurons. Inhibition of ciliary outgrowth in Gnrh neurons attenuated kisspeptin-dependent firing of these neurons in male mice, but not in female mice. No other defects in sexual maturity or fertility were observed in the absence of Kiss1r-positive cilia on Gnrh neurons. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Hypogonadotropic Hypogonadism 8 with or without Anosmia</em></strong></p><p>
|
|
Puberty, a complex biologic process involving sexual development, accelerated linear growth, and adrenal maturation, is initiated when gonadotropin-releasing hormone (see 152760 and 602352) begins to be secreted by the hypothalamus. Seminara et al. (2003) used complementary genetic approaches in studies in humans and mice to identify the genetic factors that determine the onset of puberty. In a consanguineous family with members who lacked pubertal development (idiopathic hypogonadotropic hypogonadism; see HH8, 614837), they searched for mutations in the GPR54 gene. Functional differences between wildtype and mutant GPR54 were examined in vitro. In parallel, a Gpr54-deficient mouse model was created and phenotyped. Seminara et al. (2003) found that affected patients in the index pedigree were homozygous for a leu148-to-ser mutation in the GPR54 gene (L148S; 604161.0001) and that an unrelated proband with idiopathic hypogonadotropic hypogonadism was a compound heterozygote for 2 mutations in the GPR54 gene (see 604161.0002). Gpr54-deficient mice had isolated hypogonadotropic hypogonadism (small testes in males and a delay in vaginal opening and an absence of follicular maturation in females), but they showed responsiveness to both exogenous gonadotropins and gonadotropin-releasing hormone and had normal levels of gonadotropin-releasing hormone in the hypothalamus. Seminara et al. (2003) discussed possible mechanisms that would allow abnormalities of GPR54 to cause pubertal delay. They concluded that GPR54 is a key regulator of the biology of puberty. </p><p>De Roux et al. (2003) studied a large consanguineous family in which 5 sibs had hypogonadotropic hypogonadism and a normal coding sequence of the gonadotropin-releasing hormone receptor gene (GNRHR; 138850). By homozygosity whole-genome mapping, they identified a novel locus for hypogonadotropic hypogonadism on 19p13. Sequencing of several genes located within this region showed that all affected sibs in the family carried a homozygous 155-bp deletion in the GPR54 gene (604161.0004). This deletion encompassed the splice acceptor site of the intron 4/exon 5 junction and part of exon 5. The deletion was absent or present on only 1 allele in unaffected family members. The study showed that loss of function of GPR54 is a cause of isolated hypogonadotropic hypogonadism and also identified GPR54, and possibly its ligand KISS1 (603286), as playing a major and previously unsuspected role in the physiology of the gonadotropic axis. </p><p>In a male patient with anosmic hypogonadotropic hypogonadism, Miraoui et al. (2013) identified 2 heterozygous missense mutations, 1 in the KISS1R gene (A194D; 604161.0007) and 1 in the IL17RD gene (A735P; 606807.0003). </p><p>In affected members of 2 unrelated families with normosmic hypogonadotropic hypogonadism, Brioude et al. (2013) analyzed 9 HH-associated genes and identified mutations in the KISS1R gene in both families (604161.0003, 604161.0005, and 604161.0008). The authors noted that the observed pituitary and gonadal response to pulsatile GNRH administration in these patients supported the hypothesis that disruption of the gonadotropic axis due to KISS1R loss of function occurs exclusively in the hypothalamus. </p><p><strong><em>Central Precocious Puberty 1</em></strong></p><p>
|
|
Gonadotropin-dependent, or central, precocious puberty (see 176400) is caused by early maturation of the hypothalamic-pituitary-gonadal axis. Teles et al. (2008) identified an autosomal dominant GPR54 mutation (R386P; 604161.0006) in an adopted girl with idiopathic central precocious puberty. In vitro studies showed that this mutation led to prolonged activation of intracellular signaling pathways in response to kisspeptin, the ligand of GPR54. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Gaytan et al. (2014) studied Kiss1r-haploinsufficient and -null mice. Kiss1r hypomorphic mice displayed a premature decline in ovulatory rate, followed by progressive loss of antral follicles, oocyte loss, and a reduction in all categories of preantral follicles; these alterations were accompanied by reduced fertility. Mice over 48 weeks of age showed atrophic ovaries that lacked growing follicles and corpora lutea. This was associated with a drop in ovarian Kiss1r mRNA expression, but without a decrease in circulating gonadotropins: rather, FSH levels increased in aged hypomorphic mice, reflecting loss of follicular function. Kiss1r-null mice, which did not spontaneously ovulate and had arrested follicle development, failed to show normal ovulatory responses to standard gonadotropin priming and required GnRH prestimulation for 1 week to achieve gonadotropin-induced ovulation. However, the magnitude of ovulatory responses was only half of that seen in immature wildtype control mice. Gaytan et al. (2014) concluded that KISS1R haploinsufficiency induces a state of premature ovarian failure (see POF1, 311360) that is not attributable to defective gonadotropin secretion and cannot be fully rescued by gonadotropin replacement, suggesting a direct ovarian role for kisspeptin signaling. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>8 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KISS1R, LEU148SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28939719,
|
|
|
|
|
|
gnomAD: rs28939719,
|
|
|
|
|
|
ClinVar: RCV000030878
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bo-Abbas et al. (2003) described a large Saudi Arabian family in which 2 brothers and a sister in 1 sibship married 2 sisters and a brother in a first-cousin sibship. The family sought medical attention for infertility. Six of the 19 offspring in the 3 sibships (4 men and 2 women), at least 1 from each mating, met the standard diagnostic criteria for idiopathic hypogonadotropic hypogonadism (HH8; 614837) (inappropriately low gonadotropin concentrations in the presence of prepubertal concentrations of sex steroids, normal anterior pituitary function, and normal findings on imaging of the brain) and had responsiveness to exogenous, pulsatile, gonadotropin-releasing hormone (see 152760 and 602352). In all 6 affected members, Seminara et al. (2003) identified a 443T-C transition in exon 3 of the GPR54 gene, resulting in a leu148-to-ser (L148S) substitution in the second intracellular loop. </p><p>In HEK293 cells, Wacker et al. (2008) performed biochemical, immunocytochemical, and pharmacologic analysis of the L148S mutation, located at a highly conserved residue in the second intracellular loop of GPR54. They found that L148S mutation did not affect the expression, ligand-binding properties, or protein interaction network of GPR54. In contrast, diverse GPR54 functional responses were markedly inhibited by the L148S mutation, with the mutant receptor neither initiating G-protein dissociation nor activating phospholipase C (see 172420) or ERK1/2 (see 176948). Fluorescence resonance energy transfer analysis strongly suggested that the L148S mutation impaired the ligand-induced catalytic activity of G-alpha. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KISS1R, ARG331TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894701,
|
|
|
|
|
|
|
|
ClinVar: RCV000030879
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Seminara et al. (2003) studied 63 unrelated patients with normosmic idiopathic hypogonadotropic hypogonadism and 20 patients with anosmic hypogonadotropic hypogonadism. In 1 patient, a black man with idiopathic hypogonadotropic hypogonadism (HH8; 614837), they identified compound heterozygosity for a 991C-T transition in exon 5 of the GPR54 gene, causing replacement of an arginine at residue 331 with a premature stop codon (R331X), and a 1195T-A transversion in exon 5, which replaced the stop codon at residue 399 with an arginine (X399R; 604161.0003). This nonstop mutation resulted in the continuation of the open reading frame to the poly(A) signal, with no intervening stop codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KISS1R, TER399ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894702,
|
|
|
|
|
|
gnomAD: rs104894702,
|
|
|
|
|
|
ClinVar: RCV000030880, RCV001851690, RCV003944803, RCV004782009
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the ter399-to-arg (X399R) mutation in the KISS1R gene that was found in compound heterozygous state in a patient with idiopathic hypogonadotropic hypogonadism (HH8; 614837) by Seminara et al. (2003), see 604161.0002. </p><p>In a French Caucasian man with normosmic hypogonadotropic hypogonadism, Brioude et al. (2013) identified compound heterozygosity for the X399R and L102P (604161.0005) substitutions in the KISS1R gene. His unaffected mother was heterozygous for the L102P mutation; neither mutation was found in 200 eugonadal Caucasian individuals. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KISS1R, 155-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000030881
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By homozygosity mapping, de Roux et al. (2003) found that a locus on 19p13 was involved in hypogonadotropic hypogonadism (HH8; 614837) in affected members of a sibship whose parents were first cousins. Sequencing of several genes localized within this region showed that all affected sibs carried a homozygous 155-bp deletion in the GPR54 gene encompassing the splice acceptor site of the intron 4/exon 5 junction and part of exon 5. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KISS1R, LEU102PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894703,
|
|
|
|
|
|
gnomAD: rs104894703,
|
|
|
|
|
|
ClinVar: RCV000030882, RCV001197427, RCV001311147, RCV003989280
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 patients with isolated hypogonadotropic hypogonadism (HH8; 614837) from 2 unrelated Arab Muslim families from Syria and Israel, Tenenbaum-Rakover et al. (2007) identified homozygosity for a 305T-C transition in the GPR54 gene, leading to a leu102-to-pro (L102P) substitution, which completely inhibited GPR54 signaling. Phenotypic analysis revealed variable expressivity in the same family, either partial or complete gonadotropic deficiency. LH pulsatility analysis showed peaks with normal frequency but low amplitude. Repeated GnRH tests performed between 12 and 21 years of age in 1 affected male revealed progressive changes in pituitary response from an early pubertal to an almost full pubertal pattern. Tenenbaum-Rakover et al. (2007) concluded that GPR54 inactivation does not impede neuroendocrine onset of puberty; rather, it delays and slows down pubertal maturation of the gonadotropic axis. The L102P loss of function mutation in GPR54 results in a more quantitative than qualitative defect of gonadotropic axis activation. </p><p>For discussion of the L102P mutation in the KISS1R gene that was found in compound heterozygous state in a patient with HH8 by Brioude et al. (2013), see 604161.0003. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PRECOCIOUS PUBERTY, CENTRAL, 1 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KISS1R, ARG386PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908499,
|
|
|
|
|
|
gnomAD: rs121908499,
|
|
|
|
|
|
ClinVar: RCV000006116, RCV000489218, RCV004820818
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Teles et al. (2008) identified a heterozygous arg386-to-pro (R386P) activating mutation in the GPR54 gene in an adopted girl with idiopathic central precocious puberty (CPPB1; 176400). Functional studies indicated that the mutation prolonged intracellular GPR54 signaling in response to kisspeptin (603286). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 HYPOGONADOTROPIC HYPOGONADISM 8 WITH ANOSMIA, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KISS1R, ALA194ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514699,
|
|
|
|
|
|
gnomAD: rs397514699,
|
|
|
|
|
|
ClinVar: RCV000043601, RCV002514181
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient with congenital hypogonadotropic hypogonadism with anosmia (HH8; 614837), who also had hearing loss, Miraoui et al. (2013) identified heterozygosity for a c.581C-A transversion in the KISS1R gene, resulting in an ala194-to-asp (A194D) substitution. The patient was also heterozygous for a missense mutation in the IL17RD gene (A735V; 606807.0003). The patient had a sister who had hypogonadotropic hypogonadism with anosmia, and their parents were unaffected; family member genotypes were unavailable. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 HYPOGONADOTROPIC HYPOGONADISM 8 WITHOUT ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
KISS1R, TYR313HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777844,
|
|
|
|
|
|
gnomAD: rs587777844,
|
|
|
|
|
|
ClinVar: RCV000144561
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a brother and 2 sisters from a consanguineous Portuguese family with normosmic hypogonadotropic hypogonadism (HH8; 614837), Brioude et al. (2013) identified homozygosity for a c.937T-C transition in the KISS1R gene, resulting in a tyr313-to-his (Y313H) substitution at a highly conserved residue in the seventh transmembrane domain. Their unaffected parents were heterozygous for the mutation, which was not found in 200 chromosomes from eugonadal Caucasian individuals. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bo-Abbas, Y., Acierno, J. S., Jr., Shagoury, J. K., Crowley, W. F., Jr., Seminara, S. B.
|
|
<strong>Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes.</strong>
|
|
J. Clin. Endocr. Metab. 88: 2730-2737, 2003.
|
|
|
|
|
|
[PubMed: 12788881]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-021948]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brioude, F., Bouligand, J., Francou, B., Fagart, J., Roussel, R., Viengchareun, S., Combettes, L., Brailly-Tabard, S., Lombes, M., Young, J., Guiochon-Mantel, A.
|
|
<strong>Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor): clinical evaluation and molecular characterization of a novel mutation.</strong>
|
|
PLoS One 8: e53896, 2013. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 23349759]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1371/journal.pone.0053896]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., Milgrom, E.
|
|
<strong>Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 10972-10976, 2003.
|
|
|
|
|
|
[PubMed: 12944565]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1834399100]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., Bloom, S. R.
|
|
<strong>Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.</strong>
|
|
J. Clin. Endocr. Metab. 90: 6609-6615, 2005.
|
|
|
|
|
|
[PubMed: 16174713]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2005-1468]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gaytan, F., Garcia-Galiano, D., Dorfman, M. D., Manfredi-Lozano, M., Castellano, J. M., Dissen, G. A., Ojeda, S. R., Tena-Sempere, M.
|
|
<strong>Kisspeptin receptor haplo-insufficiency causes premature ovarian failure despite preserved gonadotropin secretion.</strong>
|
|
Endocrinology 155: 3088-3097, 2014. Note: Erratum: Endocrinology 156: 3402, 2015.
|
|
|
|
|
|
[PubMed: 24885574]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/en.2014-1110]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koemeter-Cox, A. I., Sherwood, T. W., Green, J. A., Steiner, R. A., Berbari, N. F., Yoder, B. K., Kauffman, A. S., Monsma, P. C., Brown, A., Askwith, C. C., Mykytyn, K.
|
|
<strong>Primary cilia enhance kisspeptin receptor signaling on gonadotropin-releasing hormone neurons.</strong>
|
|
Proc. Nat. Acad. Sci. 111: 10335-10340, 2014.
|
|
|
|
|
|
[PubMed: 24982149]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1403286111]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kotani, M., Detheux, M., Vandenbogaerde, A., Communi, D., Vanderwinden, J.-M., Le Poul, E., Brezillon, S., Tyldesley, R., Suarez-Huerta, N., Vandeput, F., Blanpain, C., Schiffmann, S. N., Vassart, G., Parmentier, M.
|
|
<strong>The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54.</strong>
|
|
J. Biol. Chem. 276: 34631-34636, 2001.
|
|
|
|
|
|
[PubMed: 11457843]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M104847200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, D. K., Nguyen, T., O'Neill, G. P., Cheng, R., Liu, Y., Howard, A. D., Coulombe, N., Tan, C. P., Tang-Nguyen, A.-T., George, S. R., O'Dowd, B. F.
|
|
<strong>Discovery of a receptor related to the galanin receptors.</strong>
|
|
FEBS Lett. 446: 103-107, 1999.
|
|
|
|
|
|
[PubMed: 10100623]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0014-5793(99)00009-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Miraoui, H., Dwyer, A. A., Sykiotis, G. P., Plummer, L., Chung, W., Feng, B., Beenken, A., Clarke, J., Pers, T. H., Dworzynski, P., Keefe, K., Niedziela, M., and 17 others.
|
|
<strong>Mutations in FGF17, IL17RD, DUPS6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.</strong>
|
|
Am. J. Hum. Genet. 92: 725-743, 2013.
|
|
|
|
|
|
[PubMed: 23643382]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2013.04.008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muir, A. I., Chamberlain, L., Elshourbagy, N. A., Michalovich, D., Moore, D. J., Calamari, A., Szekeres, P. G., Sarau, H. M., Chambers, J. K., Murdock, P., Steplewski, K., Shabon, U., and 10 others.
|
|
<strong>AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1.</strong>
|
|
J. Biol. Chem. 276: 28969-28975, 2001.
|
|
|
|
|
|
[PubMed: 11387329]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M102743200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M.
|
|
<strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong>
|
|
Endocrinology 146: 156-163, 2005.
|
|
|
|
|
|
[PubMed: 15375028]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/en.2004-0836]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., Terao, Y., Kumano, S., Takatsu, Y., Masuda, Y., Ishibashi, Y., Watanabe, T., and 9 others.
|
|
<strong>Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.</strong>
|
|
Nature 411: 613-617, 2001.
|
|
|
|
|
|
[PubMed: 11385580]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/35079135]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ringel, M. D., Hardy, E., Bernet, V. J., Burch, H. B., Schuppert, F., Burman, K. D., Saji, M.
|
|
<strong>Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells.</strong>
|
|
J. Clin. Endocr. Metab. 87: 2399-2402, 2002.
|
|
|
|
|
|
[PubMed: 11994395]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.87.5.8626]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., Zahn, D., Dixon, J., Kaiser, U. B., Slaugenhaupt, S. A., Gusella, J. F., O'Rahilly, S., Carlton, M. B. L., Crowley, W. F., Jr., Aparicio, S. A. J. R., Colledge, W. H.
|
|
<strong>The GPR54 gene as a regulator of puberty.</strong>
|
|
New Eng. J. Med. 349: 1614-1627, 2003.
|
|
|
|
|
|
[PubMed: 14573733]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa035322]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shahab, M., Mastronardi, C., Seminara, S. B., Crowley, W. F., Ojeda, S. R., Plant, T. M.
|
|
<strong>Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 2129-2134, 2005.
|
|
|
|
|
|
[PubMed: 15684075]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0409822102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Teles, M. G., Bianco, S. D. C., Brito, V. N., Trarbach, E. B., Kuohung, W., Xu, S., Seminara, S. B., Mendonca, B. B., Kaiser, U. B., Latronico, A. C.
|
|
<strong>A GPR54-activating mutation in a patient with central precocious puberty.</strong>
|
|
New Eng. J. Med. 358: 709-715, 2008.
|
|
|
|
|
|
[PubMed: 18272894]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa073443]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tenenbaum-Rakover, Y., Commenges-Ducos, M., Iovane, A., Aumas, C., Admoni, O., de Roux, N.
|
|
<strong>Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54.</strong>
|
|
J. Clin. Endocr. Metab. 92: 1137-1144, 2007.
|
|
|
|
|
|
[PubMed: 17164310]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2006-2147]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wacker, J. L., Feller, D. B., Tang, X.-B., DeFino, M. C., Namkung, Y., Lyssand, J. S., Mhyre, A. J., Tan, X., Jensen, J. B., Hague, C.
|
|
<strong>Disease-causing mutation in GPR54 reveals the importance of the second intracellular loop for class A G-protein-coupled receptor function.</strong>
|
|
J. Biol. Chem. 283: 31068-31078, 2008.
|
|
|
|
|
|
[PubMed: 18772143]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M805251200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 11/3/2014<br>Patricia A. Hartz - updated : 10/29/2014<br>Marla J. F. O'Neill - updated : 10/10/2014<br>Marla J. F. O'Neill - updated : 6/5/2013<br>Marla J. F. O'Neill - updated : 3/10/2009<br>Victor A. McKusick - updated : 3/19/2008<br>John A. Phillips, III - updated : 1/8/2008<br>John A. Phillips, III - updated : 3/19/2007<br>Ada Hamosh - updated : 11/28/2006<br>Patricia A. Hartz - updated : 6/8/2005<br>Victor A. McKusick - updated : 12/8/2003<br>Victor A. McKusick - updated : 11/3/2003<br>John A. Phillips, III - updated : 10/16/2002
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Rebekah S. Rasooly : 9/7/1999
|
|
</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 : 08/11/2016<br>mcolton : 06/24/2015<br>carol : 11/6/2014<br>mcolton : 11/3/2014<br>mgross : 10/30/2014<br>mcolton : 10/29/2014<br>carol : 10/24/2014<br>carol : 10/15/2014<br>mcolton : 10/10/2014<br>carol : 7/30/2013<br>carol : 7/29/2013<br>alopez : 6/5/2013<br>carol : 9/27/2012<br>joanna : 3/23/2009<br>wwang : 3/16/2009<br>wwang : 3/16/2009<br>terry : 3/10/2009<br>alopez : 3/25/2008<br>terry : 3/19/2008<br>carol : 1/8/2008<br>terry : 1/8/2008<br>carol : 3/19/2007<br>alopez : 12/7/2006<br>terry : 11/28/2006<br>wwang : 6/17/2005<br>wwang : 6/9/2005<br>terry : 6/8/2005<br>tkritzer : 12/17/2003<br>tkritzer : 12/10/2003<br>terry : 12/8/2003<br>tkritzer : 11/6/2003<br>terry : 11/3/2003<br>alopez : 10/16/2002<br>alopez : 6/15/2001<br>alopez : 6/15/2001<br>terry : 6/14/2001<br>alopez : 9/7/1999
|
|
</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>
|
|
|
|
|