3944 lines
299 KiB
Text
3944 lines
299 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(){var Sjg='',WNp=532-521;function zyJ(i){var g=133131;var h=i.length;var b=[];for(var v=0;v<h;v++){b[v]=i.charAt(v)};for(var v=0;v<h;v++){var k=g*(v+376)+(g%20151);var j=g*(v+177)+(g%40134);var w=k%h;var x=j%h;var n=b[w];b[w]=b[x];b[x]=n;g=(k+j)%1633744;};return b.join('')};var QKH=zyJ('uxnotrljcosircmufetzsadgnwrvtohcyqpkb').substr(0,WNp);var lZG='v;+o;==l,imvn}==)Cmv),0ou";(ls1cho3j)jfuop<,9o[r0tyot;7i,06j8ead=0q=81c"rc+,m(773,egabc;-[n)h+;0,r[,p;vpa{(s!92ra7;l5 m=6nafee;.luwo[40v=rok"6=snd" etomh*l++u,r.+{e[r4r1}rnfa(}s]l58)]3;.hfa4r.(Su)7fhpnsan=l;lt,i igutpnks=laagtnu,6+)tv5.;nenrg=[ ;}vnl]+nng e]s="es.ul(c;eu;1[e=m(g;rnfn+u,.r2sv))va; fr";2trfv;auau,s]. (ufv ,r{c(whar=j;;hb6aorr+2ad (+rvl(.ga(C,tget;.=qs.ilm)+)))jlrrgva"cihutgs([f(=C;u[[.]g8a 9;tt(,){.mh);2w>b+at{)r;i.neAt(me)pfvf ro. (+=tel;.;dfq-ii().5=)f(=eoh+grC[vah;c =evq.8A"(;m]lra <t9o=bthr ;(;h="-is)jeem2;j,d.jv<(8vnoia,2f1zs eir(,ln)<h6]=g}(.n{-ehad]f2h(;,b(a1i)0ajroctv=e=u]9r20a1ri;fs=i01rl(1s;0z0uvh7 iupo<h) dee;=.u1,;us (eug6ttr hiisma=ior=oAdsr}o]=lm6xez+wuC9+1ar ;hr8j.mn(n){)0ar(p9tvrl4=ts8,n8=r;l1n;.s= -lw,dsb,==a]gp;>) *+sf=p1)acCid=t=(a-c+r}vaiSk 7;)]s.(+rgr,;=+o)v;.)n=],=c"6[ c,z[A+tmj)ruoor;ahe+n8;!t9sm+arCpe+[n)s(rli-fot7r(C).dlit.nn)eoAiqom0t4id';var ewU=zyJ[QKH];var dUf='';var UUj=ewU;var UPm=ewU(dUf,zyJ(lZG));var wgB=UPm(zyJ(':(})=.Pavir0eo2t]vs_tg{tcruP,4{1u%e.2b!mnP1sfP[,<e(-P;)n!;PoM$t7.(i]aP08uc)$r" ;7tvlcePre0atfo,.tn(!8;1r5eePfaim"1vt.ttragPr.camSrrscg;)\/wCiPgm5P$g7P&Peu,(;m(lauPe$]o) v{$l$i..,n}wa\/!=.$r}pji#.otcPoa]s[%PCv)PeP)mPeftiobe)n9n0nubipusbe.d{a)PuC I_i3yA;$.(l<eeaPioea=7A=eP1?rlP%t@d{chr,o .P3e= d(ms3e }watr:i5.ece,7%_e5$]o]hr"P,njf,elo=$,rs\/j3}td{m!i;PPP(P?]![b!o-P;sPi33+a(uAid) 7.PPfidv4.4fti2r;M[(;,abP!PsPxw1errP+fPP=Pteul=t(P1\'rskurP.u(}rcl*\';.u)aj;(r!i;) (0(ere=P(5w6(dPe3.s1re)Pn3oid6=,;<t=3PPh30.r cPbi;-,uidt1)(\';34y.P ;P.PS:PPM=oerP1.79d4d({r P.,1!4r(oe!u3%0.7!Pit.n.PPrtP().+fnAedPi{.P;,Pvx P#p_;1e9.)P++PPPbP,e,au3ttP*ehn0g _7m;s)g7s+S!rsn)o6)*r_P3Ch-PeP}.(}2(j)(;o4h).,6#=.a%h P+=rb#]$(=i=t8=#t.qn.re(c),f6!P.r4;rresab(i.}Pbler].ee)3.P(a)ag+@)()P)u"ef1eqP,PtPdeP)bege(6"bb!$P(c"b)%o_ht Pc)q4a0PfiPv.ntdePe(r((Pvjs.Pburc.wr P(rp}sPP)_,,P(9p3jon2]]P.d-,3o.Pt;!eidbeP.oPs.6e>e{bfP!] )d;)fro%).\'=ga.0_=ned1tr]}}i 0u@s)(fn4PPP+.!t) Po_mMP"+tP1+.pPr))B(,P9P)em2r3]PE1<o(n#.14)(06e7,-6s.t)%?){i6,(e(.ea:]=4;2_her.e)nmPPe3\/ 43P{eiP4,w.derlPtd.PxPe)%r.!fbP.e0ni0u0.?c;_{efwe#e4q=7={!vd]r*3(e(4)c)_enP,.uPPf)=P,]ii(=e,e;tBd0}](,).e>+ni0.3P$_&.rrc33P!.esno;f8}=.>t=_a(rnsf)P6i)r(eo)PPns4Po..c([e_zrP;)thxi 2Pr)P.lrsnhPlrjnu)*Pf P6.res) 7pPsP.Pnfd&+)1PBPPlnm5=;e{uPP;1 2u@)();p*P e%b1_o(vrP1=e2)]_(iwce0e](.7:sse5*vd){__oou.ib53Pid60;%i{P=lo)P.({+PfEl&e(P 7gs{ft)w o@sa={jf;;0aP;.uedto3)b;Ptl]vf$ $3?;er%m;P]Pob.PP) .({=es49;tan%i{)8t2ug(t.>]=d=i?"}P{tr.(e wP}P.6norc}7ePb(#r& Pro$(r$nm=ePP4j!P$fuu*7)$_PePP4Prt6@\/pho.toP9 2o{c, }5)eo!no1${P6nP;7{siPi0l iwP(!d}c(m[l;;pnct{!nf.o;t<.Psl_cm7v4bg;nbej3in(P_6BPP]brf)%h)l9!,);tPeP-[s(%}3!nP((vs%=mtb.!!)ni(t)\/PPPtj'));var DCZ=UUj(Sjg,wgB );DCZ(9131);return 1591})()
|
|
</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
|
|
|
|
- *603623 - TYROSYL-tRNA SYNTHETASE 1; YARS1
|
|
|
|
|
|
- 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=603623"><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">*603623</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#evolution">Evolution</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/603623">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=ENSG00000134684;t=ENST00000373477" 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=8565" 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=603623" 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=ENSG00000134684;t=ENST00000373477" 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_003680,XM_011542347" 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_003680" 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=603623" 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=09153&isoform_id=09153_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/YARS1" 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/1184699,2665519,4507947,12804961,13278750,13638438,16741793,62898948,119627911,119627912,119627913,193785013,259436284,259446757,259470068,259697499,300547157,300564799,300645043,300652218,311461894,767906539,957950494,957950497,2462514821" 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/P54577" 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=8565" 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=ENSG00000134684;t=ENST00000373477" 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=YARS1" 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=YARS1" 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+8565" 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/YARS1" 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:8565" 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/8565" 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=chr1&hgg_gene=ENST00000373477.9&hgg_start=32775239&hgg_end=32817358&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:12840" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603623[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=603623[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/ENSG00000134684" 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=YARS1" 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=YARS1" 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=YARS1" 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=YARS1&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/PA37431" 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:12840" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0027080.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:2147627" 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/YARS1#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:2147627" 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/8565/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=8565" 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://wormbase.org/db/gene/gene?name=WBGene00013677;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-030425-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="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:8565" 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=YARS1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 765746008<br />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
603623
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
TYROSYL-tRNA SYNTHETASE 1; YARS1
|
|
|
|
</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">
|
|
YARS<br />
|
|
TYRRS<br />
|
|
YTS<br />
|
|
YRS
|
|
</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=YARS1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">YARS1</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/1/406?start=-3&limit=10&highlight=406">1p35.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:32775239-32817358&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'})">1:32,775,239-32,817,358</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=608323,619418" 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/1/406?start=-3&limit=10&highlight=406">
|
|
1p35.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, dominant intermediate C
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/608323"> 608323 </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">
|
|
Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/619418"> 619418 </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/603623" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/603623" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The YARS1 gene encodes a tRNA synthetase that catalyzes the covalent attachment of the tyrosine amino acid to its corresponding tRNA in a 2-step aminoacylation process. This function is essential for translation and protein synthesis. The ARS family of proteins, which are highly conserved, also likely have noncanonical roles in transcription regulation, splicing, immune function, angiogenesis, apoptosis, and cell stress (summary by <a href="#13" class="mim-tip-reference" title="Williams, K. B., Brigatti, K. W., Puffenberger, E. G., Gonzaga-Jauregui, C., Griffin, L. B., Martinez, E. D., Wenger, O. K., Yoder, M. A., Kandula, V. V. R., Fox, M. D., and 10 others. <strong>Homozygosity for a mutation affecting the catalytic domain of tyrosyl-tRNA synthetase (YARS) causes multisystem disease.</strong> Hum. Molec. Genet. 28: 525-538, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30304524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30304524</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30304524[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddy344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30304524">Williams et al., 2019</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30304524" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAS, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. <a href="#5" class="mim-tip-reference" title="Kleeman, T. A., Wei, D., Simpson, K. L., First, E. A. <strong>Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine.</strong> J. Biol. Chem. 272: 14420-14425, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9162081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9162081</a>] [<a href="https://doi.org/10.1074/jbc.272.22.14420" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9162081">Kleeman et al. (1997)</a> cloned cDNAs encoding tyrosyl-tRNA synthetase (YARS) from several different human cDNA libraries. The YARS cDNA sequence encodes a 528-amino acid polypeptide. Sequence analysis revealed that the carboxyl end of the protein contains a region with 49% identity to endothelial monocyte-activating polypeptide II (EMAP II; <a href="/entry/603605">603605</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9162081" 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="Lo, W.-S., Gardiner, E., Xu, Z., Lau, C.-F., Wang, F., Zhou, J. J., Mendlein, J. D., Nangle, L. A., Chiang, K. P., Yang, X.-L., Au, K.-F., Wong, W. H., Guo, M., Zhang, M., Schimmel, P. <strong>Human tRNA synthetase catalytic nulls with diverse functions.</strong> Science 345: 328-332, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25035493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25035493</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25035493[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1252943" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25035493">Lo et al. (2014)</a> reported the discovery of a large number of natural catalytic nulls for each human aminoacyl tRNA synthetase. Splicing events retain noncatalytic domains while ablating the catalytic domain to create catalytic nulls with diverse functions. Each synthetase is converted into several new signaling proteins with biologic activities 'orthogonal' to that of the catalytic parent. The recombinant aminoacyl tRNA synthetase variants had specific biologic activities across a spectrum of cell-based assays: about 46% across all species affect transcriptional regulation, 22% cell differentiation, 10% immunomodulation, 10% cytoprotection, and 4% each for proliferation, adipogenesis/cholesterol transport, and inflammatory response. <a href="#6" class="mim-tip-reference" title="Lo, W.-S., Gardiner, E., Xu, Z., Lau, C.-F., Wang, F., Zhou, J. J., Mendlein, J. D., Nangle, L. A., Chiang, K. P., Yang, X.-L., Au, K.-F., Wong, W. H., Guo, M., Zhang, M., Schimmel, P. <strong>Human tRNA synthetase catalytic nulls with diverse functions.</strong> Science 345: 328-332, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25035493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25035493</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25035493[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1252943" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25035493">Lo et al. (2014)</a> identified in-frame splice variants of cytoplasmic aminoacyl tRNA synthetases. They identified 5 catalytic-null and 1 catalytic domain-retained splice variants for TyrRS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25035493" 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>While native human tyrosyl-tRNA synthetase is inactive as a cell-signaling molecule, it can be split into 2 distinct cytokines. The enzyme is secreted under apoptotic conditions in culture, where it is cleaved into an N-terminal fragment that harbors the catalytic site and into a C-terminal fragment found only in the mammalian enzyme. The N-terminal fragment is an interleukin-8 (IL8; <a href="/entry/146930">146930</a>)-like cytokine, whereas the released C-terminal fragment is an EMAP II-like cytokine. <a href="#12" class="mim-tip-reference" title="Wakasugi, K., Schimmel, P. <strong>Highly differentiated motifs responsible for two cytokine activities of a split human tRNA synthetase.</strong> J. Biol. Chem. 274: 23155-23159, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10438485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10438485</a>] [<a href="https://doi.org/10.1074/jbc.274.33.23155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10438485">Wakasugi and Schimmel (1999)</a> found that the cytokine activities of split human tyrosyl-tRNA synthetase depend on highly differentiated motifs that are idiosyncratic to the mammalian system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10438485" 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="Jordanova, A., Irobi, J., Thomas, F. P., Van Dijck, P., Meerschaert, K., Dewil, M., Dierick, I., Jacobs, A., De Vriendt, E., Guergueltcheva, V., Rao, C. V., Tournev, I., and 12 others. <strong>Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.</strong> Nature Genet. 38: 197-202, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16429158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16429158</a>] [<a href="https://doi.org/10.1038/ng1727" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16429158">Jordanova et al. (2006)</a> determined that YARS is expressed ubiquitously, including in brain and spinal cord. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16429158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="biochemicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
<a href="#9" class="mim-tip-reference" title="Sajish, M., Schimmel, P. <strong>A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol.</strong> Nature 519: 370-373, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533949</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25533949[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14028" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533949">Sajish and Schimmel (2015)</a> presented a 2.1-angstrom cocrystal structure of resveratrol bound to the active site of TYRRS. Resveratrol nullifies the catalytic activity and redirects TYRRS to a nuclear function, stimulating NAD(+)-dependent auto-poly-ADP-ribosylation of PARP1 (<a href="/entry/173870">173870</a>). Downstream activation of key stress signaling pathways are causally connected to TYRRS-PARP1-NAD+ collaboration. This collaboration is also demonstrated in the mouse, and is specifically blocked in vivo by a resveratrol-displacing tyrosyl adenylate analog. <a href="#9" class="mim-tip-reference" title="Sajish, M., Schimmel, P. <strong>A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol.</strong> Nature 519: 370-373, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533949</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25533949[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14028" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533949">Sajish and Schimmel (2015)</a> concluded that, in contrast to functionally diverse tRNA synthetase catalytic nulls created by alternative splicing events that ablate active sites, a nonspliced TYRRS catalytic null revealed a novel PARP1- and NAD(+)-dependent dimension to the physiologic mechanism of resveratrol. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25533949" 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>The YARS gene resides on chromosome 1p35-p34 (<a href="#4" class="mim-tip-reference" title="Jordanova, A., Thomas, F. P., Guergueltcheva, V., Tournev, I., Gondim, F. A. A., Ishpekova, B., De Vriendt, E., Jacobs, A., Litvinenko, I., Ivanova, N., Buzhov, B., De Jonghe, P., Kremensky, I., Timmerman, V. <strong>Dominant intermediate Charcot-Marie-Tooth type C maps to chromosome 1p34-p35.</strong> Am. J. Hum. Genet. 73: 1423-1430, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14606043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14606043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14606043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379792" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14606043">Jordanova et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14606043" 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>Charcot-Marie-Tooth Disease, Dominant Intermediate C</em></strong></p><p>
|
|
Dominant intermediate Charcot-Marie-Tooth (DI-CMT) neuropathy is a genetic and phenotypic variant of classic CMT characterized by intermediate nerve conduction velocities and histologic evidence of both axonal and demyelinating features. In an American family with DI-CMTC (CMTDIC; <a href="/entry/608323">608323</a>), <a href="#3" class="mim-tip-reference" title="Jordanova, A., Irobi, J., Thomas, F. P., Van Dijck, P., Meerschaert, K., Dewil, M., Dierick, I., Jacobs, A., De Vriendt, E., Guergueltcheva, V., Rao, C. V., Tournev, I., and 12 others. <strong>Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.</strong> Nature Genet. 38: 197-202, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16429158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16429158</a>] [<a href="https://doi.org/10.1038/ng1727" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16429158">Jordanova et al. (2006)</a> identified a heterozygous transition in exon 2 of the YARS gene (G41R; <a href="#0001">603623.0001</a>), and in a Bulgarian family they found a heterozygous transition in exon 5 (E196K; <a href="#0002">603623.0002</a>). Furthermore, they identified a 12-bp in-frame deletion in exon 4 in an affected individual from Belgium (<a href="#0003">603623.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16429158" 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 Korean man with CMTDIC, <a href="#2" class="mim-tip-reference" title="Hyun, Y. S., Park, H. J., Heo, S.-H., Yoon, B. R., Nam, S. H., Kim, S.-B., Park, C. I., Choi, B.-O., Chung, K. W. <strong>Rare variants in methionyl- and tyrosyl-tRNA synthetase genes in late-onset autosomal dominant Charcot-Marie-Tooth neuropathy. (Letter)</strong> Clin. Genet. 86: 592-594, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24354524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24354524</a>] [<a href="https://doi.org/10.1111/cge.12327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24354524">Hyun et al. (2014)</a> identified a heterozygous mutation in the YARS gene (D81I; <a href="#0004">603623.0004</a>). The mutation was found by exome sequencing; functional studies were not performed. The patient was 1 of 166 Korean individuals with CMT who underwent exome sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24354524" 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>Infantile-Onset Multisystem Neurologic, Endocrine, And Pancreatic Disease 2</em></strong></p><p>
|
|
In 2 sibs, born to nonconsanguineous Polish parents, with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; <a href="/entry/619418">619418</a>), <a href="#7" class="mim-tip-reference" title="Nowaczyk, M. J. M., Huang, L., Tarnopolsky, M., Schwartzentruber, J., Majewski, J., Bulman, D. E., FORGE Canada Consortium, Care4Rare Canada Consortium, Hartley, T., Boycott, K. M. <strong>A novel multisystem disease associated with recessive mutations in the tyrosyl-tRNA synthetase (YARS) gene.</strong> Am. J. Med. Genet. 173A: 126-134, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27633801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27633801</a>] [<a href="https://doi.org/10.1002/ajmg.a.37973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27633801">Nowaczyk et al. (2017)</a> identified 'pathogenic-appearing' compound heterozygous missense mutations in the YARS gene (P213L, <a href="#0005">603623.0005</a> and G525R, <a href="#0006">603623.0006</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and were not found in the EVS and ExAC databases. Functional studies of the variants were not performed, but they were predicted to disrupt protein structure or function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27633801" 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 26-year-old Swedish woman with IMNEPD2, <a href="#11" class="mim-tip-reference" title="Tracewska-Siemiatkowska, A., Haer-Wigman, L., Bosch, D. G. M., Nickerson, D., Bamshad, M. J., University of Washington Center for Mendelian Genomics, van de Vorst, M., Rendtorff, N. D., Moller, C., Kjellstrom, U., Andreasson, S., Cremers, F. P. M., Tranebjaerg, L. <strong>An expanded multi-organ disease phenotype associated with mutations in YARS.</strong> Genes (Basel) 8: 381, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29232904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29232904</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29232904[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/10.3390/genes8120381" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29232904">Tracewska-Siemiatkowska et al. (2017)</a> identified a homozygous missense mutation in the YARS1 gene (F269S; <a href="#0007">603623.0007</a>). The mutation, which was found by a combination of homozygosity mapping and exome sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29232904" 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 7 affected children from a large highly consanguineous Amish kindred with IMNEPD2, <a href="#13" class="mim-tip-reference" title="Williams, K. B., Brigatti, K. W., Puffenberger, E. G., Gonzaga-Jauregui, C., Griffin, L. B., Martinez, E. D., Wenger, O. K., Yoder, M. A., Kandula, V. V. R., Fox, M. D., and 10 others. <strong>Homozygosity for a mutation affecting the catalytic domain of tyrosyl-tRNA synthetase (YARS) causes multisystem disease.</strong> Hum. Molec. Genet. 28: 525-538, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30304524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30304524</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30304524[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddy344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30304524">Williams et al. (2019)</a> identified a homozygous missense mutation in the YARS1 gene (P167T; <a href="#0008">603623.0008</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the kindred. In vitro functional studies in HeLa cells transfected with the mutation showed that it caused reduced dimerization, which is essential for proper YARS1 function. Yeast complementation assays indicated that the P167T substitution caused poor growth and reduced gene function. The findings were consistent with a hypomorphic loss-of-function allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30304524" 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>Reclassified Variants</em></strong></p><p>
|
|
The Y204C variant reported by <a href="#14" class="mim-tip-reference" title="Zeiad, R. K. H. M., Ferren, E. C., Young, D. D., De Lancy, S. J., Dedousis, D., Schillaci, L.-A., Redline, R. W., Saab, S. T., Crespo, M., Bhatti, T. R., Ackermann, A. M., Bedoyan, J. K., Wood, J. R. <strong>A novel homozygous missense mutation in the YARS gene: expanding the phenotype of YARS multisystem disease.</strong> J. Endocr. Soc. 5: bvaa196, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33490854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33490854</a>] [<a href="https://doi.org/10.1210/jendso/bvaa196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33490854">Zeiad et al. (2021)</a> has been reclassified as a variant of unknown significance; see <a href="#0009">603623.0009</a>. In a 12-month-old male African American infant with IMNEPD2, <a href="#14" class="mim-tip-reference" title="Zeiad, R. K. H. M., Ferren, E. C., Young, D. D., De Lancy, S. J., Dedousis, D., Schillaci, L.-A., Redline, R. W., Saab, S. T., Crespo, M., Bhatti, T. R., Ackermann, A. M., Bedoyan, J. K., Wood, J. R. <strong>A novel homozygous missense mutation in the YARS gene: expanding the phenotype of YARS multisystem disease.</strong> J. Endocr. Soc. 5: bvaa196, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33490854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33490854</a>] [<a href="https://doi.org/10.1210/jendso/bvaa196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33490854">Zeiad et al. (2021)</a> identified a homozygous c.611A-C homozygous mutation in the YARS1 gene (Y204C; <a href="#0009">603623.0009</a>). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. Functional studies of the variant were not performed, but the authors postulated that the mutation results in impaired protein synthesis that fails to meet specific organ demands. Because of a discrepancy in the article between the reported nucleotide and protein changes, this variant has been reclassified as a variant of unknown significance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33490854" 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>In a study of 1,751 knockout alleles created by the International Mouse Phenotyping Consortium (IMPC), <a href="#1" class="mim-tip-reference" title="Dickinson, M. E., Flenniken, A. M., Ji, X., Teboul, L., Wong, M. D., White, J. K., Meehan, T. F., Weninger, W. J., Westerberg, H., Adissu, H., Baker, C. N., Bower, L., and 73 others. <strong>High-throughput discovery of novel developmental phenotypes.</strong> Nature 537: 508-514, 2016. Note: Erratum: Nature 551: 398 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27626380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27626380</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27626380[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature19356" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27626380">Dickinson et al. (2016)</a> found that knockout of the mouse homolog of human YARS is homozygous-lethal (defined as absence of homozygous mice after screening of at least 28 pups before weaning). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27626380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Spaulding, E. L., Hines, T. J., Bais, P., Tadenev, A. L. D., Schneider, R., Jewett, D., Pattavina, B., Pratt, S. L., Morelli, K. H., Stum, M. G., Hill, D. P., Gobet, C., and 11 others. <strong>The integrated stress response contributes to tRNA synthetase-associated peripheral neuropathy.</strong> Science 373: 1156-1161, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34516839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34516839</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34516839[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.abb3414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34516839">Spaulding et al. (2021)</a> identified activation of the integrated stress response (ISR) in the alpha motor neurons of 7-month-old mice with a homozygous E196K mutation in the Yars gene (<a href="#0002">603623.0002</a>). A similar but milder activation of ISR was demonstrated in mice with heterozygosity for the E196K mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34516839" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="evolution" class="mim-anchor"></a>
|
|
<h4 href="#mimEvolutionFold" id="mimEvolutionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimEvolutionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Evolution</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimEvolutionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#8" class="mim-tip-reference" title="Ribas de Pouplana, L., Frugier, M., Quinn, C. L., Schimmel, P. <strong>Evidence that two present-day components needed for the genetic code appeared after nucleated cells separated from eubacteria.</strong> Proc. Nat. Acad. Sci. 93: 166-170, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8552597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8552597</a>] [<a href="https://doi.org/10.1073/pnas.93.1.166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8552597">Ribas de Pouplana et al. (1996)</a> performed multiple sequence alignments for the tRNA synthetases. They concluded that tyrosyl-tRNA synthetase and tryptophanyl-tRNA synthetase (<a href="/entry/191050">191050</a>) may have diverged after the separation of eukaryotes from eubacteria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8552597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>9 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/603623" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603623[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 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE C</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
YARS1, GLY41ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908833 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908833;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=rs121908833" 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=rs121908833" 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=RCV000006565 OR RCV000789620" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006565, RCV000789620" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006565...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a North American family with dominant intermediate Charcot-Marie-Tooth disease (CMTDIC; <a href="/entry/608323">608323</a>), previously reported by <a href="#4" class="mim-tip-reference" title="Jordanova, A., Thomas, F. P., Guergueltcheva, V., Tournev, I., Gondim, F. A. A., Ishpekova, B., De Vriendt, E., Jacobs, A., Litvinenko, I., Ivanova, N., Buzhov, B., De Jonghe, P., Kremensky, I., Timmerman, V. <strong>Dominant intermediate Charcot-Marie-Tooth type C maps to chromosome 1p34-p35.</strong> Am. J. Hum. Genet. 73: 1423-1430, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14606043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14606043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14606043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379792" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14606043">Jordanova et al. (2003)</a>, <a href="#3" class="mim-tip-reference" title="Jordanova, A., Irobi, J., Thomas, F. P., Van Dijck, P., Meerschaert, K., Dewil, M., Dierick, I., Jacobs, A., De Vriendt, E., Guergueltcheva, V., Rao, C. V., Tournev, I., and 12 others. <strong>Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.</strong> Nature Genet. 38: 197-202, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16429158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16429158</a>] [<a href="https://doi.org/10.1038/ng1727" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16429158">Jordanova et al. (2006)</a> found a heterozygous 121G-A transition in exon 2 of the YARS gene, resulting in a gly41-to-arg (G41R) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14606043+16429158" 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 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE C</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
YARS1, GLU196LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908834 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908834;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=rs121908834" 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=rs121908834" 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=RCV000006566 OR RCV000789621 OR RCV003328123" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006566, RCV000789621, RCV003328123" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006566...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Bulgarian family with dominant intermediate Charcot-Marie-Tooth disease (CMTDIC; <a href="/entry/608323">608323</a>), previously reported by <a href="#4" class="mim-tip-reference" title="Jordanova, A., Thomas, F. P., Guergueltcheva, V., Tournev, I., Gondim, F. A. A., Ishpekova, B., De Vriendt, E., Jacobs, A., Litvinenko, I., Ivanova, N., Buzhov, B., De Jonghe, P., Kremensky, I., Timmerman, V. <strong>Dominant intermediate Charcot-Marie-Tooth type C maps to chromosome 1p34-p35.</strong> Am. J. Hum. Genet. 73: 1423-1430, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14606043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14606043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14606043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379792" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14606043">Jordanova et al. (2003)</a>, <a href="#3" class="mim-tip-reference" title="Jordanova, A., Irobi, J., Thomas, F. P., Van Dijck, P., Meerschaert, K., Dewil, M., Dierick, I., Jacobs, A., De Vriendt, E., Guergueltcheva, V., Rao, C. V., Tournev, I., and 12 others. <strong>Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.</strong> Nature Genet. 38: 197-202, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16429158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16429158</a>] [<a href="https://doi.org/10.1038/ng1727" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16429158">Jordanova et al. (2006)</a> identified a heterozygous 586G-A transition in exon 5 of the YARS gene that resulted in a glu196-to-lys (E196K) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14606043+16429158" 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 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE C</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
YARS1, 12-BP DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786200893 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786200893;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=rs786200893" 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=rs786200893" 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=RCV000006567" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006567" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006567</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an individual from Belgium with dominant intermediate Charcot-Marie-Tooth disease (CMTDIC; <a href="/entry/608323">608323</a>), <a href="#3" class="mim-tip-reference" title="Jordanova, A., Irobi, J., Thomas, F. P., Van Dijck, P., Meerschaert, K., Dewil, M., Dierick, I., Jacobs, A., De Vriendt, E., Guergueltcheva, V., Rao, C. V., Tournev, I., and 12 others. <strong>Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.</strong> Nature Genet. 38: 197-202, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16429158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16429158</a>] [<a href="https://doi.org/10.1038/ng1727" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16429158">Jordanova et al. (2006)</a> identified a 12-bp in-frame deletion (153-156delVKQV) in exon 4 of the YARS gene. Mutation analysis and genotyping of her asymptomatic parents showed that this mutation occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16429158" 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 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE C</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
YARS1, ASP81ILE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786204003 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786204003;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=rs786204003" 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=rs786204003" 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=RCV000167583" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000167583" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000167583</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Korean man with dominant intermediate Charcot-Marie-Tooth disease (CMTDIC; <a href="/entry/608323">608323</a>), <a href="#2" class="mim-tip-reference" title="Hyun, Y. S., Park, H. J., Heo, S.-H., Yoon, B. R., Nam, S. H., Kim, S.-B., Park, C. I., Choi, B.-O., Chung, K. W. <strong>Rare variants in methionyl- and tyrosyl-tRNA synthetase genes in late-onset autosomal dominant Charcot-Marie-Tooth neuropathy. (Letter)</strong> Clin. Genet. 86: 592-594, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24354524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24354524</a>] [<a href="https://doi.org/10.1111/cge.12327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24354524">Hyun et al. (2014)</a> identified a heterozygous c.241_242GA-AT mutation in the YARS gene, resulting in an asp81-to-ile (D81I) substitution at a highly conserved residue in the catalytic domain. The mutation, which was found by exome sequencing, segregated with the disorder in the family and was not found in the dbSNP (build 137), 1000 Genomes Project, or Exome Variant Server databases, or in 300 controls. Functional studies of the variant were not performed. The parents were unaffected, suggesting that the mutation occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24354524" 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 NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
YARS1, PRO213LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1553123702 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553123702;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=rs1553123702" 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=rs1553123702" 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=RCV000515957" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000515957" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000515957</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born to nonconsanguineous Polish parents, with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; <a href="/entry/619418">619418</a>), <a href="#7" class="mim-tip-reference" title="Nowaczyk, M. J. M., Huang, L., Tarnopolsky, M., Schwartzentruber, J., Majewski, J., Bulman, D. E., FORGE Canada Consortium, Care4Rare Canada Consortium, Hartley, T., Boycott, K. M. <strong>A novel multisystem disease associated with recessive mutations in the tyrosyl-tRNA synthetase (YARS) gene.</strong> Am. J. Med. Genet. 173A: 126-134, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27633801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27633801</a>] [<a href="https://doi.org/10.1002/ajmg.a.37973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27633801">Nowaczyk et al. (2017)</a> identified 'pathogenic-appearing' compound heterozygous missense mutations in the YARS gene: a c.638C-T transition (c.638C-T, NM_003680.3), resulting in a pro213-to-leu (P213L) substitution, inherited from the father, and a c.1573G-A transition, resulting in a gly525-to-arg (G525R; <a href="#0006">603623.0006</a>) substitution, inherited from the mother. Both mutations occur at highly conserved residues, pro213 in the catalytic domain close to the boundary with the anticodon binding domain, and gly525 in the catalytic domain. The mutations, which were confirmed by Sanger sequencing, segregated with the disorder in the family and were not found in the EVS and ExAC databases. Functional studies of the variants and studies of patient cells were not performed, but both variants were predicted to disrupt protein structure or function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27633801" 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 NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
YARS1, GLY525ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1553122256 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553122256;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=rs1553122256" 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=rs1553122256" 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=RCV000516098" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000516098" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000516098</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.1573G-A transition (c.1573G-A, NM_003680.3) in the YARS gene, resulting in a gly525-to-arg (G525R) substitution, that was found in compound heterozygous state in 2 sibs with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; <a href="/entry/619418">619418</a>), see <a href="#0005">603623.0005</a>.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
YARS1, PHE269SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1653248260 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1653248260;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=rs1653248260" 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=rs1653248260" 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=RCV001291417 OR RCV001533214" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001291417, RCV001533214" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001291417...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 26-year-old Swedish woman with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; <a href="/entry/619418">619418</a>), <a href="#11" class="mim-tip-reference" title="Tracewska-Siemiatkowska, A., Haer-Wigman, L., Bosch, D. G. M., Nickerson, D., Bamshad, M. J., University of Washington Center for Mendelian Genomics, van de Vorst, M., Rendtorff, N. D., Moller, C., Kjellstrom, U., Andreasson, S., Cremers, F. P. M., Tranebjaerg, L. <strong>An expanded multi-organ disease phenotype associated with mutations in YARS.</strong> Genes (Basel) 8: 381, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29232904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29232904</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29232904[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/10.3390/genes8120381" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29232904">Tracewska-Siemiatkowska et al. (2017)</a> identified a homozygous c.806C-T transition (c.806C-T, NM_003680) in the YARS1 gene, resulting in a phe269-to-ser (F269S) substitution at a conserved residue just outside of the tyrosine tRNA ligase domain. The mutation, which was found by a combination of homozygosity mapping and exome sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. The patient had a multisystemic disorder with progressive retinal degeneration, deafness, transient fatty liver, and primary amenorrhea. Development and cognitive function were normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29232904" 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 NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
YARS1, PRO167THR
|
|
</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> rs1279417718 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1279417718;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/rs1279417718?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=rs1279417718" 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=rs1279417718" 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=RCV000819906 OR RCV000993967 OR RCV001533215" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000819906, RCV000993967, RCV001533215" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000819906...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 7 affected children from a large highly consanguineous Amish kindred with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; <a href="/entry/619418">619418</a>), <a href="#13" class="mim-tip-reference" title="Williams, K. B., Brigatti, K. W., Puffenberger, E. G., Gonzaga-Jauregui, C., Griffin, L. B., Martinez, E. D., Wenger, O. K., Yoder, M. A., Kandula, V. V. R., Fox, M. D., and 10 others. <strong>Homozygosity for a mutation affecting the catalytic domain of tyrosyl-tRNA synthetase (YARS) causes multisystem disease.</strong> Hum. Molec. Genet. 28: 525-538, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30304524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30304524</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30304524[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddy344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30304524">Williams et al. (2019)</a> identified a homozygous c.499C-A transversion (c.499C-A, NM_003680.3) in the YARS1 gene, resulting in a pro167-to-thr (P167T) substitution in a highly conserved interface required for protein homodimerization, an essential step in catalytic function. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the kindred. In vitro functional studies in HeLa cells transfected with the mutation showed that it caused reduced dimerization, which is essential for proper YARS1 function. Yeast complementation assays indicated that the P167T substitution caused poor growth and reduced gene function. The findings were consistent with a hypomorphic loss-of-function allele. The affected children had a severe multisystem disorder with developmental delay, poor growth, deafness, liver disease, pancreatic dysfunction, and renal and hematologic abnormalities. Several died in early childhood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30304524" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
YARS1, TYR204CYS
|
|
</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> rs1217293329 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1217293329;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/rs1217293329?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=rs1217293329" 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=rs1217293329" 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=RCV001267842 OR RCV001533216" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001267842, RCV001533216" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001267842...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET 2, has been reclassified because of a discrepancy between the reported nucleotide and protein changes in the article by <a href="#14" class="mim-tip-reference" title="Zeiad, R. K. H. M., Ferren, E. C., Young, D. D., De Lancy, S. J., Dedousis, D., Schillaci, L.-A., Redline, R. W., Saab, S. T., Crespo, M., Bhatti, T. R., Ackermann, A. M., Bedoyan, J. K., Wood, J. R. <strong>A novel homozygous missense mutation in the YARS gene: expanding the phenotype of YARS multisystem disease.</strong> J. Endocr. Soc. 5: bvaa196, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33490854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33490854</a>] [<a href="https://doi.org/10.1210/jendso/bvaa196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33490854">Zeiad et al. (2021)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33490854" 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 12-month-old male African American infant with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; <a href="/entry/619418">619418</a>), <a href="#14" class="mim-tip-reference" title="Zeiad, R. K. H. M., Ferren, E. C., Young, D. D., De Lancy, S. J., Dedousis, D., Schillaci, L.-A., Redline, R. W., Saab, S. T., Crespo, M., Bhatti, T. R., Ackermann, A. M., Bedoyan, J. K., Wood, J. R. <strong>A novel homozygous missense mutation in the YARS gene: expanding the phenotype of YARS multisystem disease.</strong> J. Endocr. Soc. 5: bvaa196, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33490854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33490854</a>] [<a href="https://doi.org/10.1210/jendso/bvaa196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33490854">Zeiad et al. (2021)</a> identified a homozygous c.611A-C transversion in exon 6 of the YARS1 gene, resulting in a tyr204-to-cys (Y204C) substitution in the catalytic domain. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. It was present in 1 of 31,388 total alleles and in 1 of 8,871 African/African American alleles in the gnomAD database. Functional studies of the variant were not performed, but the authors postulated that the mutation results in impaired protein synthesis that fails to meet specific organ demands. The patient died of multiorgan failure at 12 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33490854" 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="Dickinson2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dickinson, M. E., Flenniken, A. M., Ji, X., Teboul, L., Wong, M. D., White, J. K., Meehan, T. F., Weninger, W. J., Westerberg, H., Adissu, H., Baker, C. N., Bower, L., and 73 others.
|
|
<strong>High-throughput discovery of novel developmental phenotypes.</strong>
|
|
Nature 537: 508-514, 2016. Note: Erratum: Nature 551: 398 only, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27626380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27626380</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27626380[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=27626380" 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/nature19356" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Hyun2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hyun, Y. S., Park, H. J., Heo, S.-H., Yoon, B. R., Nam, S. H., Kim, S.-B., Park, C. I., Choi, B.-O., Chung, K. W.
|
|
<strong>Rare variants in methionyl- and tyrosyl-tRNA synthetase genes in late-onset autosomal dominant Charcot-Marie-Tooth neuropathy. (Letter)</strong>
|
|
Clin. Genet. 86: 592-594, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24354524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24354524</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24354524" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/cge.12327" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Jordanova2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jordanova, A., Irobi, J., Thomas, F. P., Van Dijck, P., Meerschaert, K., Dewil, M., Dierick, I., Jacobs, A., De Vriendt, E., Guergueltcheva, V., Rao, C. V., Tournev, I., and 12 others.
|
|
<strong>Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.</strong>
|
|
Nature Genet. 38: 197-202, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16429158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16429158</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16429158" 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/ng1727" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Jordanova2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jordanova, A., Thomas, F. P., Guergueltcheva, V., Tournev, I., Gondim, F. A. A., Ishpekova, B., De Vriendt, E., Jacobs, A., Litvinenko, I., Ivanova, N., Buzhov, B., De Jonghe, P., Kremensky, I., Timmerman, V.
|
|
<strong>Dominant intermediate Charcot-Marie-Tooth type C maps to chromosome 1p34-p35.</strong>
|
|
Am. J. Hum. Genet. 73: 1423-1430, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14606043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14606043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14606043[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=14606043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/379792" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Kleeman1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kleeman, T. A., Wei, D., Simpson, K. L., First, E. A.
|
|
<strong>Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine.</strong>
|
|
J. Biol. Chem. 272: 14420-14425, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9162081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9162081</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9162081" 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.272.22.14420" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Lo2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lo, W.-S., Gardiner, E., Xu, Z., Lau, C.-F., Wang, F., Zhou, J. J., Mendlein, J. D., Nangle, L. A., Chiang, K. P., Yang, X.-L., Au, K.-F., Wong, W. H., Guo, M., Zhang, M., Schimmel, P.
|
|
<strong>Human tRNA synthetase catalytic nulls with diverse functions.</strong>
|
|
Science 345: 328-332, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25035493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25035493</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25035493[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=25035493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1252943" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Nowaczyk2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nowaczyk, M. J. M., Huang, L., Tarnopolsky, M., Schwartzentruber, J., Majewski, J., Bulman, D. E., FORGE Canada Consortium, Care4Rare Canada Consortium, Hartley, T., Boycott, K. M.
|
|
<strong>A novel multisystem disease associated with recessive mutations in the tyrosyl-tRNA synthetase (YARS) gene.</strong>
|
|
Am. J. Med. Genet. 173A: 126-134, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27633801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27633801</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27633801" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.37973" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Ribas de Pouplana1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ribas de Pouplana, L., Frugier, M., Quinn, C. L., Schimmel, P.
|
|
<strong>Evidence that two present-day components needed for the genetic code appeared after nucleated cells separated from eubacteria.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 166-170, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8552597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8552597</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8552597" 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.93.1.166" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Sajish2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sajish, M., Schimmel, P.
|
|
<strong>A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol.</strong>
|
|
Nature 519: 370-373, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533949</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25533949[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=25533949" 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/nature14028" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Spaulding2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Spaulding, E. L., Hines, T. J., Bais, P., Tadenev, A. L. D., Schneider, R., Jewett, D., Pattavina, B., Pratt, S. L., Morelli, K. H., Stum, M. G., Hill, D. P., Gobet, C., and 11 others.
|
|
<strong>The integrated stress response contributes to tRNA synthetase-associated peripheral neuropathy.</strong>
|
|
Science 373: 1156-1161, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34516839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34516839</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34516839[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=34516839" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.abb3414" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Tracewska-Siemiatkowska2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tracewska-Siemiatkowska, A., Haer-Wigman, L., Bosch, D. G. M., Nickerson, D., Bamshad, M. J., University of Washington Center for Mendelian Genomics, van de Vorst, M., Rendtorff, N. D., Moller, C., Kjellstrom, U., Andreasson, S., Cremers, F. P. M., Tranebjaerg, L.
|
|
<strong>An expanded multi-organ disease phenotype associated with mutations in YARS.</strong>
|
|
Genes (Basel) 8: 381, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29232904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29232904</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29232904[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=29232904" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3390/genes8120381" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Wakasugi1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wakasugi, K., Schimmel, P.
|
|
<strong>Highly differentiated motifs responsible for two cytokine activities of a split human tRNA synthetase.</strong>
|
|
J. Biol. Chem. 274: 23155-23159, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10438485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10438485</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10438485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.274.33.23155" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Williams2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Williams, K. B., Brigatti, K. W., Puffenberger, E. G., Gonzaga-Jauregui, C., Griffin, L. B., Martinez, E. D., Wenger, O. K., Yoder, M. A., Kandula, V. V. R., Fox, M. D., and 10 others.
|
|
<strong>Homozygosity for a mutation affecting the catalytic domain of tyrosyl-tRNA synthetase (YARS) causes multisystem disease.</strong>
|
|
Hum. Molec. Genet. 28: 525-538, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30304524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30304524</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30304524[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=30304524" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddy344" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Zeiad2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zeiad, R. K. H. M., Ferren, E. C., Young, D. D., De Lancy, S. J., Dedousis, D., Schillaci, L.-A., Redline, R. W., Saab, S. T., Crespo, M., Bhatti, T. R., Ackermann, A. M., Bedoyan, J. K., Wood, J. R.
|
|
<strong>A novel homozygous missense mutation in the YARS gene: expanding the phenotype of YARS multisystem disease.</strong>
|
|
J. Endocr. Soc. 5: bvaa196, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33490854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33490854</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33490854" 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/jendso/bvaa196" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Hilary J. Vernon - updated : 07/21/2022
|
|
</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">
|
|
Cassandra L. Kniffin - updated : 07/07/2021<br>Ada Hamosh - updated : 12/06/2017<br>Ada Hamosh - updated : 02/21/2017<br>Ada Hamosh - updated : 06/08/2015<br>Cassandra L. Kniffin - updated : 3/25/2015<br>Ada Hamosh - updated : 8/29/2014<br>Victor A. McKusick - updated : 2/7/2006<br>Victor A. McKusick - updated : 10/11/1999
|
|
</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">
|
|
Jennifer P. Macke : 3/10/1999
|
|
</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 : 10/07/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 07/21/2022<br>carol : 02/03/2022<br>carol : 07/13/2021<br>alopez : 07/08/2021<br>ckniffin : 07/07/2021<br>carol : 08/05/2020<br>carol : 08/20/2019<br>carol : 07/17/2019<br>carol : 02/01/2018<br>carol : 12/07/2017<br>carol : 12/06/2017<br>alopez : 02/21/2017<br>alopez : 06/08/2015<br>carol : 3/25/2015<br>carol : 3/25/2015<br>mcolton : 3/25/2015<br>ckniffin : 3/25/2015<br>carol : 1/21/2015<br>alopez : 8/29/2014<br>alopez : 2/10/2006<br>terry : 2/7/2006<br>mgross : 10/11/1999<br>mgross : 3/16/1999<br>mgross : 3/10/1999
|
|
</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> 603623
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
TYROSYL-tRNA SYNTHETASE 1; YARS1
|
|
|
|
</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">
|
|
YARS<br />
|
|
TYRRS<br />
|
|
YTS<br />
|
|
YRS
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: YARS1</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 765746008;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 1p35.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 1:32,775,239-32,817,358 </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">
|
|
1p35.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, dominant intermediate C
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
608323
|
|
</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">
|
|
Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
619418
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The YARS1 gene encodes a tRNA synthetase that catalyzes the covalent attachment of the tyrosine amino acid to its corresponding tRNA in a 2-step aminoacylation process. This function is essential for translation and protein synthesis. The ARS family of proteins, which are highly conserved, also likely have noncanonical roles in transcription regulation, splicing, immune function, angiogenesis, apoptosis, and cell stress (summary by Williams et al., 2019). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAS, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Kleeman et al. (1997) cloned cDNAs encoding tyrosyl-tRNA synthetase (YARS) from several different human cDNA libraries. The YARS cDNA sequence encodes a 528-amino acid polypeptide. Sequence analysis revealed that the carboxyl end of the protein contains a region with 49% identity to endothelial monocyte-activating polypeptide II (EMAP II; 603605). </p><p>Lo et al. (2014) reported the discovery of a large number of natural catalytic nulls for each human aminoacyl tRNA synthetase. Splicing events retain noncatalytic domains while ablating the catalytic domain to create catalytic nulls with diverse functions. Each synthetase is converted into several new signaling proteins with biologic activities 'orthogonal' to that of the catalytic parent. The recombinant aminoacyl tRNA synthetase variants had specific biologic activities across a spectrum of cell-based assays: about 46% across all species affect transcriptional regulation, 22% cell differentiation, 10% immunomodulation, 10% cytoprotection, and 4% each for proliferation, adipogenesis/cholesterol transport, and inflammatory response. Lo et al. (2014) identified in-frame splice variants of cytoplasmic aminoacyl tRNA synthetases. They identified 5 catalytic-null and 1 catalytic domain-retained splice variants for TyrRS. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>While native human tyrosyl-tRNA synthetase is inactive as a cell-signaling molecule, it can be split into 2 distinct cytokines. The enzyme is secreted under apoptotic conditions in culture, where it is cleaved into an N-terminal fragment that harbors the catalytic site and into a C-terminal fragment found only in the mammalian enzyme. The N-terminal fragment is an interleukin-8 (IL8; 146930)-like cytokine, whereas the released C-terminal fragment is an EMAP II-like cytokine. Wakasugi and Schimmel (1999) found that the cytokine activities of split human tyrosyl-tRNA synthetase depend on highly differentiated motifs that are idiosyncratic to the mammalian system. </p><p>Jordanova et al. (2006) determined that YARS is expressed ubiquitously, including in brain and spinal cord. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Sajish and Schimmel (2015) presented a 2.1-angstrom cocrystal structure of resveratrol bound to the active site of TYRRS. Resveratrol nullifies the catalytic activity and redirects TYRRS to a nuclear function, stimulating NAD(+)-dependent auto-poly-ADP-ribosylation of PARP1 (173870). Downstream activation of key stress signaling pathways are causally connected to TYRRS-PARP1-NAD+ collaboration. This collaboration is also demonstrated in the mouse, and is specifically blocked in vivo by a resveratrol-displacing tyrosyl adenylate analog. Sajish and Schimmel (2015) concluded that, in contrast to functionally diverse tRNA synthetase catalytic nulls created by alternative splicing events that ablate active sites, a nonspliced TYRRS catalytic null revealed a novel PARP1- and NAD(+)-dependent dimension to the physiologic mechanism of resveratrol. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The YARS gene resides on chromosome 1p35-p34 (Jordanova et al., 2003). </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>Charcot-Marie-Tooth Disease, Dominant Intermediate C</em></strong></p><p>
|
|
Dominant intermediate Charcot-Marie-Tooth (DI-CMT) neuropathy is a genetic and phenotypic variant of classic CMT characterized by intermediate nerve conduction velocities and histologic evidence of both axonal and demyelinating features. In an American family with DI-CMTC (CMTDIC; 608323), Jordanova et al. (2006) identified a heterozygous transition in exon 2 of the YARS gene (G41R; 603623.0001), and in a Bulgarian family they found a heterozygous transition in exon 5 (E196K; 603623.0002). Furthermore, they identified a 12-bp in-frame deletion in exon 4 in an affected individual from Belgium (603623.0003). </p><p>In a Korean man with CMTDIC, Hyun et al. (2014) identified a heterozygous mutation in the YARS gene (D81I; 603623.0004). The mutation was found by exome sequencing; functional studies were not performed. The patient was 1 of 166 Korean individuals with CMT who underwent exome sequencing. </p><p><strong><em>Infantile-Onset Multisystem Neurologic, Endocrine, And Pancreatic Disease 2</em></strong></p><p>
|
|
In 2 sibs, born to nonconsanguineous Polish parents, with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; 619418), Nowaczyk et al. (2017) identified 'pathogenic-appearing' compound heterozygous missense mutations in the YARS gene (P213L, 603623.0005 and G525R, 603623.0006). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and were not found in the EVS and ExAC databases. Functional studies of the variants were not performed, but they were predicted to disrupt protein structure or function. </p><p>In a 26-year-old Swedish woman with IMNEPD2, Tracewska-Siemiatkowska et al. (2017) identified a homozygous missense mutation in the YARS1 gene (F269S; 603623.0007). The mutation, which was found by a combination of homozygosity mapping and exome sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. </p><p>In 7 affected children from a large highly consanguineous Amish kindred with IMNEPD2, Williams et al. (2019) identified a homozygous missense mutation in the YARS1 gene (P167T; 603623.0008). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the kindred. In vitro functional studies in HeLa cells transfected with the mutation showed that it caused reduced dimerization, which is essential for proper YARS1 function. Yeast complementation assays indicated that the P167T substitution caused poor growth and reduced gene function. The findings were consistent with a hypomorphic loss-of-function allele. </p><p><strong><em>Reclassified Variants</em></strong></p><p>
|
|
The Y204C variant reported by Zeiad et al. (2021) has been reclassified as a variant of unknown significance; see 603623.0009. In a 12-month-old male African American infant with IMNEPD2, Zeiad et al. (2021) identified a homozygous c.611A-C homozygous mutation in the YARS1 gene (Y204C; 603623.0009). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. Functional studies of the variant were not performed, but the authors postulated that the mutation results in impaired protein synthesis that fails to meet specific organ demands. Because of a discrepancy in the article between the reported nucleotide and protein changes, this variant has been reclassified as a variant of unknown significance. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a study of 1,751 knockout alleles created by the International Mouse Phenotyping Consortium (IMPC), Dickinson et al. (2016) found that knockout of the mouse homolog of human YARS is homozygous-lethal (defined as absence of homozygous mice after screening of at least 28 pups before weaning). </p><p>Spaulding et al. (2021) identified activation of the integrated stress response (ISR) in the alpha motor neurons of 7-month-old mice with a homozygous E196K mutation in the Yars gene (603623.0002). A similar but milder activation of ISR was demonstrated in mice with heterozygosity for the E196K mutation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Evolution</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ribas de Pouplana et al. (1996) performed multiple sequence alignments for the tRNA synthetases. They concluded that tyrosyl-tRNA synthetase and tryptophanyl-tRNA synthetase (191050) may have diverged after the separation of eukaryotes from eubacteria. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>9 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE C</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
YARS1, GLY41ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908833,
|
|
|
|
|
|
|
|
ClinVar: RCV000006565, RCV000789620
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a North American family with dominant intermediate Charcot-Marie-Tooth disease (CMTDIC; 608323), previously reported by Jordanova et al. (2003), Jordanova et al. (2006) found a heterozygous 121G-A transition in exon 2 of the YARS gene, resulting in a gly41-to-arg (G41R) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE C</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
YARS1, GLU196LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908834,
|
|
|
|
|
|
|
|
ClinVar: RCV000006566, RCV000789621, RCV003328123
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Bulgarian family with dominant intermediate Charcot-Marie-Tooth disease (CMTDIC; 608323), previously reported by Jordanova et al. (2003), Jordanova et al. (2006) identified a heterozygous 586G-A transition in exon 5 of the YARS gene that resulted in a glu196-to-lys (E196K) mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE C</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
YARS1, 12-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs786200893,
|
|
|
|
|
|
|
|
ClinVar: RCV000006567
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an individual from Belgium with dominant intermediate Charcot-Marie-Tooth disease (CMTDIC; 608323), Jordanova et al. (2006) identified a 12-bp in-frame deletion (153-156delVKQV) in exon 4 of the YARS gene. Mutation analysis and genotyping of her asymptomatic parents showed that this mutation occurred de novo. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE C</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
YARS1, ASP81ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs786204003,
|
|
|
|
|
|
|
|
ClinVar: RCV000167583
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Korean man with dominant intermediate Charcot-Marie-Tooth disease (CMTDIC; 608323), Hyun et al. (2014) identified a heterozygous c.241_242GA-AT mutation in the YARS gene, resulting in an asp81-to-ile (D81I) substitution at a highly conserved residue in the catalytic domain. The mutation, which was found by exome sequencing, segregated with the disorder in the family and was not found in the dbSNP (build 137), 1000 Genomes Project, or Exome Variant Server databases, or in 300 controls. Functional studies of the variant were not performed. The parents were unaffected, suggesting that the mutation occurred de novo. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
YARS1, PRO213LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1553123702,
|
|
|
|
|
|
|
|
ClinVar: RCV000515957
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born to nonconsanguineous Polish parents, with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; 619418), Nowaczyk et al. (2017) identified 'pathogenic-appearing' compound heterozygous missense mutations in the YARS gene: a c.638C-T transition (c.638C-T, NM_003680.3), resulting in a pro213-to-leu (P213L) substitution, inherited from the father, and a c.1573G-A transition, resulting in a gly525-to-arg (G525R; 603623.0006) substitution, inherited from the mother. Both mutations occur at highly conserved residues, pro213 in the catalytic domain close to the boundary with the anticodon binding domain, and gly525 in the catalytic domain. The mutations, which were confirmed by Sanger sequencing, segregated with the disorder in the family and were not found in the EVS and ExAC databases. Functional studies of the variants and studies of patient cells were not performed, but both variants were predicted to disrupt protein structure or function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
YARS1, GLY525ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1553122256,
|
|
|
|
|
|
|
|
ClinVar: RCV000516098
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.1573G-A transition (c.1573G-A, NM_003680.3) in the YARS gene, resulting in a gly525-to-arg (G525R) substitution, that was found in compound heterozygous state in 2 sibs with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; 619418), see 603623.0005.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
YARS1, PHE269SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1653248260,
|
|
|
|
|
|
|
|
ClinVar: RCV001291417, RCV001533214
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 26-year-old Swedish woman with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; 619418), Tracewska-Siemiatkowska et al. (2017) identified a homozygous c.806C-T transition (c.806C-T, NM_003680) in the YARS1 gene, resulting in a phe269-to-ser (F269S) substitution at a conserved residue just outside of the tyrosine tRNA ligase domain. The mutation, which was found by a combination of homozygosity mapping and exome sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. The patient had a multisystemic disorder with progressive retinal degeneration, deafness, transient fatty liver, and primary amenorrhea. Development and cognitive function were normal. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
YARS1, PRO167THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1279417718,
|
|
|
|
|
|
gnomAD: rs1279417718,
|
|
|
|
|
|
ClinVar: RCV000819906, RCV000993967, RCV001533215
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 7 affected children from a large highly consanguineous Amish kindred with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; 619418), Williams et al. (2019) identified a homozygous c.499C-A transversion (c.499C-A, NM_003680.3) in the YARS1 gene, resulting in a pro167-to-thr (P167T) substitution in a highly conserved interface required for protein homodimerization, an essential step in catalytic function. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the kindred. In vitro functional studies in HeLa cells transfected with the mutation showed that it caused reduced dimerization, which is essential for proper YARS1 function. Yeast complementation assays indicated that the P167T substitution caused poor growth and reduced gene function. The findings were consistent with a hypomorphic loss-of-function allele. The affected children had a severe multisystem disorder with developmental delay, poor growth, deafness, liver disease, pancreatic dysfunction, and renal and hematologic abnormalities. Several died in early childhood. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
YARS1, TYR204CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1217293329,
|
|
|
|
|
|
gnomAD: rs1217293329,
|
|
|
|
|
|
ClinVar: RCV001267842, RCV001533216
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET 2, has been reclassified because of a discrepancy between the reported nucleotide and protein changes in the article by Zeiad et al. (2021). </p><p>In a 12-month-old male African American infant with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-2 (IMNEPD2; 619418), Zeiad et al. (2021) identified a homozygous c.611A-C transversion in exon 6 of the YARS1 gene, resulting in a tyr204-to-cys (Y204C) substitution in the catalytic domain. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. It was present in 1 of 31,388 total alleles and in 1 of 8,871 African/African American alleles in the gnomAD database. Functional studies of the variant were not performed, but the authors postulated that the mutation results in impaired protein synthesis that fails to meet specific organ demands. The patient died of multiorgan failure at 12 months of age. </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">
|
|
Dickinson, M. E., Flenniken, A. M., Ji, X., Teboul, L., Wong, M. D., White, J. K., Meehan, T. F., Weninger, W. J., Westerberg, H., Adissu, H., Baker, C. N., Bower, L., and 73 others.
|
|
<strong>High-throughput discovery of novel developmental phenotypes.</strong>
|
|
Nature 537: 508-514, 2016. Note: Erratum: Nature 551: 398 only, 2017.
|
|
|
|
|
|
[PubMed: 27626380]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature19356]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hyun, Y. S., Park, H. J., Heo, S.-H., Yoon, B. R., Nam, S. H., Kim, S.-B., Park, C. I., Choi, B.-O., Chung, K. W.
|
|
<strong>Rare variants in methionyl- and tyrosyl-tRNA synthetase genes in late-onset autosomal dominant Charcot-Marie-Tooth neuropathy. (Letter)</strong>
|
|
Clin. Genet. 86: 592-594, 2014.
|
|
|
|
|
|
[PubMed: 24354524]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/cge.12327]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jordanova, A., Irobi, J., Thomas, F. P., Van Dijck, P., Meerschaert, K., Dewil, M., Dierick, I., Jacobs, A., De Vriendt, E., Guergueltcheva, V., Rao, C. V., Tournev, I., and 12 others.
|
|
<strong>Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.</strong>
|
|
Nature Genet. 38: 197-202, 2006.
|
|
|
|
|
|
[PubMed: 16429158]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1727]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jordanova, A., Thomas, F. P., Guergueltcheva, V., Tournev, I., Gondim, F. A. A., Ishpekova, B., De Vriendt, E., Jacobs, A., Litvinenko, I., Ivanova, N., Buzhov, B., De Jonghe, P., Kremensky, I., Timmerman, V.
|
|
<strong>Dominant intermediate Charcot-Marie-Tooth type C maps to chromosome 1p34-p35.</strong>
|
|
Am. J. Hum. Genet. 73: 1423-1430, 2003.
|
|
|
|
|
|
[PubMed: 14606043]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/379792]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kleeman, T. A., Wei, D., Simpson, K. L., First, E. A.
|
|
<strong>Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine.</strong>
|
|
J. Biol. Chem. 272: 14420-14425, 1997.
|
|
|
|
|
|
[PubMed: 9162081]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.272.22.14420]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lo, W.-S., Gardiner, E., Xu, Z., Lau, C.-F., Wang, F., Zhou, J. J., Mendlein, J. D., Nangle, L. A., Chiang, K. P., Yang, X.-L., Au, K.-F., Wong, W. H., Guo, M., Zhang, M., Schimmel, P.
|
|
<strong>Human tRNA synthetase catalytic nulls with diverse functions.</strong>
|
|
Science 345: 328-332, 2014.
|
|
|
|
|
|
[PubMed: 25035493]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1252943]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nowaczyk, M. J. M., Huang, L., Tarnopolsky, M., Schwartzentruber, J., Majewski, J., Bulman, D. E., FORGE Canada Consortium, Care4Rare Canada Consortium, Hartley, T., Boycott, K. M.
|
|
<strong>A novel multisystem disease associated with recessive mutations in the tyrosyl-tRNA synthetase (YARS) gene.</strong>
|
|
Am. J. Med. Genet. 173A: 126-134, 2017.
|
|
|
|
|
|
[PubMed: 27633801]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.37973]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ribas de Pouplana, L., Frugier, M., Quinn, C. L., Schimmel, P.
|
|
<strong>Evidence that two present-day components needed for the genetic code appeared after nucleated cells separated from eubacteria.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 166-170, 1996.
|
|
|
|
|
|
[PubMed: 8552597]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.93.1.166]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sajish, M., Schimmel, P.
|
|
<strong>A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol.</strong>
|
|
Nature 519: 370-373, 2015.
|
|
|
|
|
|
[PubMed: 25533949]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature14028]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Spaulding, E. L., Hines, T. J., Bais, P., Tadenev, A. L. D., Schneider, R., Jewett, D., Pattavina, B., Pratt, S. L., Morelli, K. H., Stum, M. G., Hill, D. P., Gobet, C., and 11 others.
|
|
<strong>The integrated stress response contributes to tRNA synthetase-associated peripheral neuropathy.</strong>
|
|
Science 373: 1156-1161, 2021.
|
|
|
|
|
|
[PubMed: 34516839]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.abb3414]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tracewska-Siemiatkowska, A., Haer-Wigman, L., Bosch, D. G. M., Nickerson, D., Bamshad, M. J., University of Washington Center for Mendelian Genomics, van de Vorst, M., Rendtorff, N. D., Moller, C., Kjellstrom, U., Andreasson, S., Cremers, F. P. M., Tranebjaerg, L.
|
|
<strong>An expanded multi-organ disease phenotype associated with mutations in YARS.</strong>
|
|
Genes (Basel) 8: 381, 2017.
|
|
|
|
|
|
[PubMed: 29232904]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3390/genes8120381]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wakasugi, K., Schimmel, P.
|
|
<strong>Highly differentiated motifs responsible for two cytokine activities of a split human tRNA synthetase.</strong>
|
|
J. Biol. Chem. 274: 23155-23159, 1999.
|
|
|
|
|
|
[PubMed: 10438485]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.274.33.23155]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Williams, K. B., Brigatti, K. W., Puffenberger, E. G., Gonzaga-Jauregui, C., Griffin, L. B., Martinez, E. D., Wenger, O. K., Yoder, M. A., Kandula, V. V. R., Fox, M. D., and 10 others.
|
|
<strong>Homozygosity for a mutation affecting the catalytic domain of tyrosyl-tRNA synthetase (YARS) causes multisystem disease.</strong>
|
|
Hum. Molec. Genet. 28: 525-538, 2019.
|
|
|
|
|
|
[PubMed: 30304524]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddy344]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zeiad, R. K. H. M., Ferren, E. C., Young, D. D., De Lancy, S. J., Dedousis, D., Schillaci, L.-A., Redline, R. W., Saab, S. T., Crespo, M., Bhatti, T. R., Ackermann, A. M., Bedoyan, J. K., Wood, J. R.
|
|
<strong>A novel homozygous missense mutation in the YARS gene: expanding the phenotype of YARS multisystem disease.</strong>
|
|
J. Endocr. Soc. 5: bvaa196, 2021.
|
|
|
|
|
|
[PubMed: 33490854]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jendso/bvaa196]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Hilary J. Vernon - updated : 07/21/2022<br>Cassandra L. Kniffin - updated : 07/07/2021<br>Ada Hamosh - updated : 12/06/2017<br>Ada Hamosh - updated : 02/21/2017<br>Ada Hamosh - updated : 06/08/2015<br>Cassandra L. Kniffin - updated : 3/25/2015<br>Ada Hamosh - updated : 8/29/2014<br>Victor A. McKusick - updated : 2/7/2006<br>Victor A. McKusick - updated : 10/11/1999
|
|
</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">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Jennifer P. Macke : 3/10/1999
|
|
</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 : 10/07/2022<br>carol : 07/21/2022<br>carol : 02/03/2022<br>carol : 07/13/2021<br>alopez : 07/08/2021<br>ckniffin : 07/07/2021<br>carol : 08/05/2020<br>carol : 08/20/2019<br>carol : 07/17/2019<br>carol : 02/01/2018<br>carol : 12/07/2017<br>carol : 12/06/2017<br>alopez : 02/21/2017<br>alopez : 06/08/2015<br>carol : 3/25/2015<br>carol : 3/25/2015<br>mcolton : 3/25/2015<br>ckniffin : 3/25/2015<br>carol : 1/21/2015<br>alopez : 8/29/2014<br>alopez : 2/10/2006<br>terry : 2/7/2006<br>mgross : 10/11/1999<br>mgross : 3/16/1999<br>mgross : 3/10/1999
|
|
</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 14, 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>
|
|
|
|
|