5921 lines
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Entry
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- *300075 - RIBOSOMAL PROTEIN S6 KINASE A3; RPS6KA3
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*300075</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/300075">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<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">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000177189;t=ENST00000379565" 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>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=6197" 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>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=300075" 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>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000177189;t=ENST00000379565" 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>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_004586,XM_005274573,XM_005274577,XM_011545555,XM_011545556,XM_011545557,XM_011545560,XM_011545561,XM_011545562,XM_017029717,XM_017029718,XM_017029719,XM_047442332,XM_047442333,XM_047442334,XM_047442335,XM_047442336" 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>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_004586" 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>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=300075" 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>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=02092&isoform_id=02092_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>
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<div><a href="https://www.proteinatlas.org/search/RPS6KA3" 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>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/401774,475588,1730070,4759050,19421917,33353423,33353425,33353427,33353429,33353431,33353433,33353435,33353437,33353439,33353441,33353443,33353445,33353447,33353449,33353451,33353453,33353455,33353457,33353459,33353461,33353483,33353485,33353487,33353489,33353491,33353493,33353495,33353497,33353499,33353501,33353503,33353505,33353507,33353509,33353511,33353513,33353515,33353517,33353519,33353521,33353543,33353545,33353547,33353549,33353551,33353553,33353555,33353557,33353559,33353561,33353563,33353565,33353567,33353569,33353571,33353573,33353575,33353577,33353579,33353581,33354095,62087446,64653293,64654466,64654862,189054131,194377370,194383992,221046352,308219974,530421219,530421227,768032625,768032629,768032635,768032646,768032651,768032654,1034674905,1034674907,1034674910,2217393515,2217393518,2217393525,2217393527,2217393531,2462630414,2462630416,2462630418,2462630420,2462630422,2462630424,2462630426,2462630428,2462630430,2462630432,2462630434,2462630436,2462630438,2462630440,2462630442,2462630444,2462630446" 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>
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<div><a href="https://www.uniprot.org/uniprotkb/P51812" 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>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=6197" 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>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000177189;t=ENST00000379565" 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>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=RPS6KA3" 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>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=RPS6KA3" 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>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+6197" 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>
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<dd><a href="http://v1.marrvel.org/search/gene/RPS6KA3" 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>
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<dd><a href="https://monarchinitiative.org/NCBIGene:6197" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/6197" 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>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chrX&hgg_gene=ENST00000379565.9&hgg_start=20149911&hgg_end=20267097&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>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:10432" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:10432" 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>
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<div><a href="https://medlineplus.gov/genetics/gene/rps6ka3" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=300075[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>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300075[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>
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<div><a href="https://www.deciphergenomics.org/gene/RPS6KA3/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000177189" 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>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=RPS6KA3" 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>
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<div><a href="https://www.gwascentral.org/search?q=RPS6KA3" 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>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=RPS6KA3" 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>
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<div><a href="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://alsace.u-strasbg.fr/chimbio/diag/coffin/index.html" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Coffin-Lowry Syndrome</a></div><div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/RPS6KA3" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">RPS6KA3 database at LOVD</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=RPS6KA3&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>
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<div><a href="https://www.pharmgkb.org/gene/PA34847" 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>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:10432" 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>
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<div><a href="https://flybase.org/reports/FBgn0262866.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>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:104557" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/RPS6KA3#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>
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<div><a href="http://www.informatics.jax.org/marker/MGI:104557" 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>
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<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>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/6197/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>
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<div><a href="https://www.orthodb.org/?ncbi=6197" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00011352;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>
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<div><a href="https://zfin.org/ZDB-GENE-030219-119" 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>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:6197" 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>
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<div><a href="https://reactome.org/content/query?q=RPS6KA3&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>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<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.">
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</span>
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</span>
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</div>
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<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">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 15182000<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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300075
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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RIBOSOMAL PROTEIN S6 KINASE A3; RPS6KA3
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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RIBOSOMAL PROTEIN S6 KINASE, 90-KD, 3<br />
|
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RIBOSOMAL S6 KINASE 2; RSK2<br />
|
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MITOGEN-ACTIVATED PROTEIN KINASE-ACTIVATED PROTEIN KINASE 1B; MAPKAPK1B<br />
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MAPKAP KINASE 1B<br />
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ISPK1
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=RPS6KA3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">RPS6KA3</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
|
Cytogenetic location: <a href="/geneMap/X/109?start=-3&limit=10&highlight=109">Xp22.12</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:20149911-20267097&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'})">X:20,149,911-20,267,097</a> </span>
|
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</em>
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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Intellectual developmental disorder, X-linked 19
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PheneGene Graphics <span class="caret"></span>
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<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>
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<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.">
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<p>The RPS6KA3 gene encodes a member of the RSK (ribosomal S6 kinase) family of growth factor-regulated serine/threonine kinases, known also as p90(rsk). RSK proteins contain 2 functional kinase catalytic domains: the N-terminal kinase domain belongs to the AGC kinase family (see <a href="/entry/188830">188830</a>), and the C-terminal kinase domain belongs to the CamK family (see <a href="/entry/604998">604998</a>). The kinase domains are connected by a 100-amino acid linker region containing a PDK (PDPK1; <a href="/entry/605213">605213</a>) docking site. RSK proteins are directly phosphorylated and activated by MAPK proteins (e.g., ERK1; <a href="/entry/601795">601795</a>) in response to growth factors, polypeptide hormones, and neurotransmitters, and then subsequently phosphorylate many substrates. RSKs appear to have important roles in cell cycle progression, differentiation, and cell survival (review by <a href="#17" class="mim-tip-reference" title="Marques Pereira, P., Schneider, A., Pannetier, S., Heron, D., Hanauer, A. <strong>Coffin-Lowry syndrome.</strong> Europ. J. Hum. Genet. 18: 627-633, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19888300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19888300</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19888300[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2009.189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19888300">Marques Pereira et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19888300" 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>
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<p><a href="#2" class="mim-tip-reference" title="Bjorbaek, C., Vik, T. A., Echwald, S. M., Yang, P.-Y., Vestergaard, H., Wang, J. P., Webb, G. C., Richmond, K., Hansen, T., Erikson, R. L., Gabor Miklos, G. L., Cohen, P. T. W., Pederson, O. <strong>Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients.</strong> Diabetes 44: 90-97, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7813820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7813820</a>] [<a href="https://doi.org/10.2337/diab.44.1.90" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7813820">Bjorbaek et al. (1995)</a> showed that the cDNA encoding RPS6KA3, which they called ISPK1, encodes a predicted protein of 740 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7813820" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Zeniou, M., Ding, T., Trivier, E., Hanauer, A. <strong>Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning.</strong> Hum. Molec. Genet. 11: 2929-2940, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393804</a>] [<a href="https://doi.org/10.1093/hmg/11.23.2929" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393804">Zeniou et al. (2002)</a> determined the expression of the RSK1 (RPS6KA1; <a href="/entry/601684">601684</a>), RSK2, and RSK3 (RPS6KA2; <a href="/entry/601685">601685</a>) genes in various human tissues, during mouse embryogenesis, and in mouse brain. The 3 RSK mRNAs were expressed in all human tissues and brain regions tested, supporting functional redundancy. However, tissue-specific variations in levels suggested that the proteins may also serve specific roles. The mouse Rsk3 gene was prominently expressed in the developing neural and sensory tissues, whereas Rsk1 gene expression was the strongest in various other tissues with high proliferative activity, suggesting distinct roles during development. In adult mouse brain, the highest levels of Rsk2 expression were observed in regions with high synaptic activity, including the neocortex, the hippocampus, and Purkinje cells. The authors suggested that in these areas, which are essential to cognitive function and learning, the RSK1 and RSK3 genes may not be able to fully compensate for a lack of RSK2 function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393804" 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>
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<strong>Gene Structure</strong>
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<p><a href="#11" class="mim-tip-reference" title="Jacquot, S., Merienne, K., De Cesare, D., Pannetier, S., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A. <strong>Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations.</strong> Am. J. Hum. Genet. 63: 1631-1640, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837815</a>] [<a href="https://doi.org/10.1086/302153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837815">Jacquot et al. (1998)</a> found that the open reading frame of the RPS6KA3 coding region contains 22 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837815" 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>
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<strong>Mapping</strong>
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<p>In a study of the region of the X chromosome (Xp22.2) within which the Coffin-Lowry syndrome (CLS; <a href="/entry/303600">303600</a>) maps, <a href="#27" class="mim-tip-reference" title="Trivier, E., De Cesare, D., Jacquot, S., Pannetier, S., Zackai, E., Young, I., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A. <strong>Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.</strong> Nature 384: 567-570, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8955270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8955270</a>] [<a href="https://doi.org/10.1038/384567a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8955270">Trivier et al. (1996)</a> identified an expressed sequence tag (EST) that showed 100% homology with a cDNA coding for RPS6KA3. Its localization was independently confirmed by <a href="#2" class="mim-tip-reference" title="Bjorbaek, C., Vik, T. A., Echwald, S. M., Yang, P.-Y., Vestergaard, H., Wang, J. P., Webb, G. C., Richmond, K., Hansen, T., Erikson, R. L., Gabor Miklos, G. L., Cohen, P. T. W., Pederson, O. <strong>Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients.</strong> Diabetes 44: 90-97, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7813820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7813820</a>] [<a href="https://doi.org/10.2337/diab.44.1.90" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7813820">Bjorbaek et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8955270+7813820" 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>
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<p>During the immediate-early response of mammalian cells to mitogens, histone H3 (see <a href="/entry/602810">602810</a>) is rapidly and transiently phosphorylated by one or more kinases. <a href="#25" class="mim-tip-reference" title="Sassone-Corsi, P., Mizzen, C. A., Cheung, P., Crosjo, C., Monaco, L., Jacquot, S., Hanauer, A., Allis, C. D. <strong>Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3.</strong> Science 285: 886-891, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10436156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10436156</a>] [<a href="https://doi.org/10.1126/science.285.5429.886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10436156">Sassone-Corsi et al. (1999)</a> demonstrated that RSK2 was required for epidermal growth factor (EGF; <a href="/entry/131530">131530</a>)-stimulated phosphorylation of H3. Fibroblasts derived from a CLS patient failed to exhibit EGF-stimulated phosphorylation of H3, although H3 was phosphorylated during mitosis. Introduction of the wildtype RSK2 gene restored EGF-stimulated phosphorylation of H3 in the CLS cells. In addition, disruption of the RSK2 gene by homologous recombination in murine embryonic stem cells abolished EGF-stimulated phosphorylation of H3. H3 appears to be a direct or indirect target of RSK2, suggesting to <a href="#25" class="mim-tip-reference" title="Sassone-Corsi, P., Mizzen, C. A., Cheung, P., Crosjo, C., Monaco, L., Jacquot, S., Hanauer, A., Allis, C. D. <strong>Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3.</strong> Science 285: 886-891, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10436156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10436156</a>] [<a href="https://doi.org/10.1126/science.285.5429.886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10436156">Sassone-Corsi et al. (1999)</a> that chromatin remodeling might contribute to mitogen-activated protein kinase-regulated gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10436156" 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="#26" class="mim-tip-reference" title="Thomas, G. M., Rumbaugh, G. R., Harrar, D. B., Huganir, R. L. <strong>Ribosomal S6 kinase 2 interacts with and phosphorylates PDZ domain-containing proteins and regulates AMPA receptor transmission.</strong> Proc. Nat. Acad. Sci. 102: 15006-15011, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16217014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16217014</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16217014[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0507476102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16217014">Thomas et al. (2005)</a> presented evidence suggesting that RSK2 is involved in regulation of excitatory AMPA receptor synaptic transmission by interacting with and phosphorylating PDZ domain-containing proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16217014" 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>Spindle assembly checkpoint (SAC) prevents anaphase onset until all chromosomes have successfully attached to spindle microtubules. Using Xenopus egg extracts and HeLa cells, <a href="#28" class="mim-tip-reference" title="Vigneron, S., Brioudes, E., Burgess, A., Labbe, J.-C., Lorca, T., Castro, A. <strong>RSK2 is a kinetochore-associated protein that participates in the spindle assembly checkpoint.</strong> Oncogene 29: 3566-3574, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20383198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20383198</a>] [<a href="https://doi.org/10.1038/onc.2010.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20383198">Vigneron et al. (2010)</a> found that RSK2 had a role in spindle assembly checkpoint. RSK2 localized to kinetochores during SAC. Immunofluorescence analysis and knockdown studies revealed that RSK2 and Aurora B (AURKB; <a href="/entry/604970">604970</a>) depended upon each other for kinetochore localization. Association of RSK2 at kinetochores was required to maintain SAC activation and localization of MAD1 (MXD1; <a href="/entry/600021">600021</a>), MAD2 (MAD2L1; <a href="/entry/601467">601467</a>), and CENPE (<a href="/entry/117143">117143</a>) at kinetochores. Expression of Xenopus Rsk2 rescued the effects of RSK2 knockdown in HeLa cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20383198" 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="#33" class="mim-tip-reference" title="Zhou, W., Cao, H., Yang, X., Cong, K., Wang, W., Chen, T., Yin, H., Wu, Z., Cai, X., Liu, T., Xiao, J. <strong>Characterization of nuclear localization signal in the N terminus of integrin-linked kinase-associated phosphatase (ILKAP) and its essential role in the down-regulation of RSK2 protein signaling.</strong> J. Biol. Chem. 288: 6259-6271, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23329845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23329845</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23329845[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M112.432195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23329845">Zhou et al. (2013)</a> found that ILKAP (<a href="/entry/618909">618909</a>) interacted with RSK2 in the nucleus and inhibited its activity. Inhibition of RSK2 kinase activity induced apoptosis by reducing expression of the RSK2 downstream factor cyclin D1 (CCND1; <a href="/entry/168461">168461</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23329845" 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>
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<p><strong><em>Coffin-Lowry Syndrome</em></strong></p><p>
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The localization of the RSK2 gene within the Coffin-Lowry syndrome (CLS; <a href="/entry/303600">303600</a>) interval, together with its role in signaling pathways, prompted <a href="#27" class="mim-tip-reference" title="Trivier, E., De Cesare, D., Jacquot, S., Pannetier, S., Zackai, E., Young, I., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A. <strong>Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.</strong> Nature 384: 567-570, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8955270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8955270</a>] [<a href="https://doi.org/10.1038/384567a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8955270">Trivier et al. (1996)</a> to investigate its possible implication in CLS. Patient samples from 76 families were screened, and 1 patient was found to have a genomic deletion of approximately 2 kb. Amplification by RT-PCR of cDNA from the patient and direct sequencing showed a deletion of 187 bp between nucleotide positions 406 and 593 (<a href="#0001">300075.0001</a>). The deletion produced a frameshift, generating a TAA termination codon 33 bp downstream of the deletion junction. The mutation cosegregated with CLS in 2 affected males and 1 female with discrete manifestations in this family. <a href="#27" class="mim-tip-reference" title="Trivier, E., De Cesare, D., Jacquot, S., Pannetier, S., Zackai, E., Young, I., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A. <strong>Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.</strong> Nature 384: 567-570, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8955270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8955270</a>] [<a href="https://doi.org/10.1038/384567a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8955270">Trivier et al. (1996)</a> then searched for point mutations and found both nonsense and missense mutations. Tissue-specific differences in gene expression suggested distinct physiologic roles for the various members of the RSK family (<a href="#22" class="mim-tip-reference" title="Moller, D. E., Xia, C. H., Tang, W., Zhu, A. X., Jakubowski, M. <strong>Human rsk isoforms: cloning and characterization of tissue-specific expression.</strong> Am. J. Physiol. 266: C351-C359, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8141249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8141249</a>] [<a href="https://doi.org/10.1152/ajpcell.1994.266.2.C351" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8141249">Moller et al., 1994</a>; <a href="#32" class="mim-tip-reference" title="Zhao, Y., Bjorbaek, C., Weremowicz, S., Morton, C. C., Moller, D. E. <strong>RSK3 encodes a novel pp90rsk isoform with a unique N-terminal sequence: growth factor-stimulated kinase function and nuclear translocation.</strong> Molec. Cell. Biol. 15: 4353-4363, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7623830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7623830</a>] [<a href="https://doi.org/10.1128/MCB.15.8.4353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7623830">Zhao et al., 1995</a>). RSK3 differs with respect to substrate specificity from other RSKs and may also have distinct upstream activators. <a href="#27" class="mim-tip-reference" title="Trivier, E., De Cesare, D., Jacquot, S., Pannetier, S., Zackai, E., Young, I., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A. <strong>Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.</strong> Nature 384: 567-570, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8955270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8955270</a>] [<a href="https://doi.org/10.1038/384567a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8955270">Trivier et al. (1996)</a> noted that in CLS, RSK1 and RSK3 are expressed at levels equivalent to those in normal individuals, indicating that they are not capable of overcoming the RSK2 deficiency. However, no abnormality of glycogen metabolism was found in CLS patients, although RSK2 was shown to be responsible for the activation of glycogen synthesis (<a href="#6" class="mim-tip-reference" title="Dent, P., Lavoinne, A., Nekielny, S., Caudwell, F. B., Watt, P., Cohen, P. <strong>The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle.</strong> Nature 348: 302-308, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2123524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2123524</a>] [<a href="https://doi.org/10.1038/348302a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2123524">Dent et al., 1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2123524+8141249+8955270+7623830" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Jacquot, S., Merienne, K., De Cesare, D., Pannetier, S., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A. <strong>Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations.</strong> Am. J. Hum. Genet. 63: 1631-1640, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837815</a>] [<a href="https://doi.org/10.1086/302153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837815">Jacquot et al. (1998)</a> designed primers for PCR amplification of single exons from genomic DNA and subsequent SSCP analysis. They screened 37 patients with clinical features suggestive of CLS; 25 nucleotide changes predicted to be disease-causing mutations were identified, including 8 splice site alterations, 7 nonsense mutations, 5 frameshift mutations, and 5 missense mutations. Of the 25 mutations, 23 were novel. Coupled with previously reported mutations, these findings brought the total of different RSK2 mutations to 34. These were distributed throughout the RSK2 gene, with no clustering, and all but 2, which were found in 2 independent patients, were unique. A very high (68%) rate of de novo mutations was observed. Three mutations were found in female probands with no affected male relatives; these patients were ascertained through learning disability and mild but suggestive facial and digital dysmorphisms. No obvious correlation was observed between the position or type of the RSK2 mutations and the severity or particular clinical features of CLS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Abidi, F., Jacquot, S., Lassiter, C., Trivier, E., Hanauer, A., Schwartz, C. E. <strong>Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).</strong> Europ. J. Hum. Genet. 7: 20-26, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094187</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094187">Abidi et al. (1999)</a> tested 5 unrelated individuals with CLS for mutations in 9 exons of the RSK2 gene using SSCP analysis. Two patients had the same missense mutation, 340C-T, predicted to cause an arg114-to-trp amino acid change (<a href="#0006">300075.0006</a>). This mutation falls just outside the N-terminal ATP-binding site in a highly conserved region of the protein and may lead to structural changes since tryptophan has an aromatic side chain whereas arginine is a 5-carbon basic amino acid. The third patient had a 2186G-A nucleotide change, resulting in an arg729-to-gln missense mutation (<a href="#0009">300075.0009</a>). The fourth patient had a 2-bp deletion (AG) of bases 451 and 452 (<a href="#0007">300075.0007</a>). This created a frameshift that resulted in a stop codon 25 amino acids downstream, thereby producing a truncated protein. This deletion also falls within the highly conserved amino-catalytic domain of the protein. The fifth patient had a 2065C-T nucleotide change that resulted in a premature stop codon, thereby producing a truncated protein (<a href="#0008">300075.0008</a>). Three of the patients in whom RSK2 mutations were identified by <a href="#1" class="mim-tip-reference" title="Abidi, F., Jacquot, S., Lassiter, C., Trivier, E., Hanauer, A., Schwartz, C. E. <strong>Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).</strong> Europ. J. Hum. Genet. 7: 20-26, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094187</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094187">Abidi et al. (1999)</a> had at least 1 brother who also carried the diagnosis of CLS. One of the 5 patients had a family history of mental retardation in male relatives, and his mother and aunt had been assessed as having intellectual impairment. All of the probands had large, soft hands with tapering fingers, severe to moderate mental retardation, short stature below the 5th centile, weight below the 5th centile, microcephaly, telecanthus or hypertelorism, and prominent eyes. Two were Caucasian; in these probands large mouth and prominent lower lips were observed. For the 3 African American probands this was difficult to evaluate because of the ethnic background. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094187" 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="Harum, K. H., Alemi, L., Johnston, M. V. <strong>Cognitive impairment in Coffin-Lowry syndrome correlates with reduced RSK2 activation.</strong> Neurology 56: 207-214, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11160957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11160957</a>] [<a href="https://doi.org/10.1212/wnl.56.2.207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11160957">Harum et al. (2001)</a> noted that, based on evidence from experimental models, the transcription factor cAMP response element-binding protein (CREB; <a href="/entry/123810">123810</a>) is thought to be involved in memory formation. RSK2 activates CREB through phosphorylation at serine-133. In 7 patients with CLS (5 boys and 2 girls), <a href="#10" class="mim-tip-reference" title="Harum, K. H., Alemi, L., Johnston, M. V. <strong>Cognitive impairment in Coffin-Lowry syndrome correlates with reduced RSK2 activation.</strong> Neurology 56: 207-214, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11160957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11160957</a>] [<a href="https://doi.org/10.1212/wnl.56.2.207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11160957">Harum et al. (2001)</a> found a diminished activity of RSK2 to phosphorylate a CREB-like peptide in vitro in all cells lines. The authors noted a linear correlation between RSK2 activation of CREB and cognitive levels of the patients, consistent with the hypothesis that CREB is involved in human learning and memory. Other characteristics of the syndrome, including facial and bony abnormalities, may be due to impaired expression of various CREB-responsive genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11160957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By screening 250 patients with clinical features suggestive of Coffin-Lowry syndrome, <a href="#5" class="mim-tip-reference" title="Delaunoy, J.-P., Abidi, F., Zeniou, M., Jacquot, S., Merienne, K., Pannetier, S., Schmitt, M., Schwartz, C. E., Hanauer, A. <strong>Mutations in the X-linked RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome.</strong> Hum. Mutat. 17: 103-116, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11180593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11180593</a>] [<a href="https://doi.org/10.1002/1098-1004(200102)17:2<103::AID-HUMU2>3.0.CO;2-N" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11180593">Delaunoy et al. (2001)</a> identified 71 distinct disease-associated RSK2 mutations in 86 unrelated families; 38% of the mutations were missense mutations, 20% were nonsense mutations, 18% were splicing errors, and 21% were short deletions or insertions. About 57% of the mutations resulted in premature translation termination, and most predicted loss of function of the mutant allele. The changes were distributed throughout the RSK2 gene and showed no obvious clustering or phenotypic association. However, some missense mutations were associated with milder phenotypes; in 1 family, 1 such mutation was associated solely with mild mental retardation. Nine mutations were found in female probands, with no affected male relatives, who had learning disability and mild facial and digital dysmorphism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11180593" 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="#31" class="mim-tip-reference" title="Zeniou, M., Pannetier, S., Fryns, J.-P., Hanauer, A. <strong>Unusual splice-site mutations in the RSK2 gene and suggestion of genetic heterogeneity in Coffin-Lowry syndrome.</strong> Am. J. Hum. Genet. 70: 1421-1433, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992250</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992250[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/10.1086/340607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11992250">Zeniou et al. (2002)</a> pointed out that in a series of 250 patients screened by SSCP analysis in whom the clinical diagnosis of CLS was made (<a href="#5" class="mim-tip-reference" title="Delaunoy, J.-P., Abidi, F., Zeniou, M., Jacquot, S., Merienne, K., Pannetier, S., Schmitt, M., Schwartz, C. E., Hanauer, A. <strong>Mutations in the X-linked RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome.</strong> Hum. Mutat. 17: 103-116, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11180593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11180593</a>] [<a href="https://doi.org/10.1002/1098-1004(200102)17:2<103::AID-HUMU2>3.0.CO;2-N" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11180593">Delaunoy et al., 2001</a>), no mutations were detected in 165 (66%). To determine what proportion of these latter patients had an RSK2 mutation that had not been detected and what proportion have different disorders that are phenotypically similar to CLS, <a href="#31" class="mim-tip-reference" title="Zeniou, M., Pannetier, S., Fryns, J.-P., Hanauer, A. <strong>Unusual splice-site mutations in the RSK2 gene and suggestion of genetic heterogeneity in Coffin-Lowry syndrome.</strong> Am. J. Hum. Genet. 70: 1421-1433, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992250</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992250[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/10.1086/340607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11992250">Zeniou et al. (2002)</a> investigated, by Western blot analysis and in vitro kinase assay, cell lines from 26 patients in whom no mutation was previously identified by SSCP analysis. This approach allowed them to identify 7 novel RSK2 mutations: 2 changes in the coding sequence of RSK2, 1 intragenic deletion, and 4 unusual intronic nucleotide substitutions that did not affect the consensus GT or AG splice sites. No disease-causing nucleotide change was identified in the promoter region of the RSK2 gene. The results suggested that some patients have a disorder that is phenotypically very similar to CLS but is not caused by RSK2 defects. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11180593+11992250" 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="#4" class="mim-tip-reference" title="Delaunoy, J. P., Dubos, A., Marques Pereira, P., Hanauer, A. <strong>Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome.</strong> Clin. Genet. 70: 161-166, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16879200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16879200</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00660.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16879200">Delaunoy et al. (2006)</a> analyzed the RPS6KA3 gene in 120 patients with CLS and identified 45 mutations, of which 44 were novel, confirming the high rate of new mutations at the RSK2 locus. The authors noted that no mutation was found in over 60% of the patients referred to them for screening. <a href="#4" class="mim-tip-reference" title="Delaunoy, J. P., Dubos, A., Marques Pereira, P., Hanauer, A. <strong>Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome.</strong> Clin. Genet. 70: 161-166, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16879200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16879200</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00660.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16879200">Delaunoy et al. (2006)</a> stated that of the 128 CLS mutations reported to date, 33% are missense mutations, 15% nonsense mutations, 20% splicing errors, and 29% short deletion or insertion events; and 4 large deletions have been reported. The mutations are distributed throughout the RPS6KA3 gene, and most mutations are private. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16879200" 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 patient with a clinical phenotype highly suggestive of CLS in whom no mutation had been identified by sequencing PCR-amplified exons of RPS6KA3 from genomic DNA, <a href="#16" class="mim-tip-reference" title="Marques Pereira, P., Heron, D., Hanauer, A. <strong>The first large duplication of the RSK2 gene identified in a Coffin-Lowry syndrome patient.</strong> Hum. Genet. 122: 541-543, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17717706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17717706</a>] [<a href="https://doi.org/10.1007/s00439-007-0424-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17717706">Marques Pereira et al. (2007)</a> analyzed the gene by direct sequencing of overlapping RT-PCR products and identified a direct tandem duplication spanning exactly exons 17 to 20 (<a href="#0019">300075.0019</a>). The authors stated that this was the first reported large duplication in the RPS6KA3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17717706" 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>X-Linked Intellectual Developmental Disorder 19</em></strong></p><p>
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In affected members of a family with nonsyndromic X-linked intellectual developmental disorder-19 (XLID19; <a href="/entry/300844">300844</a>), <a href="#21" class="mim-tip-reference" title="Merienne, K., Jacquot, S., Pannetier, S., Zeniou, M., Bankier, A., Gecz, J., Mandel, J.-L., Mulley, J., Sassone-Corsi, P., Hanauer, A. <strong>A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation. (Letter)</strong> Nature Genet. 22: 13-14, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10319851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10319851</a>] [<a href="https://doi.org/10.1038/8719" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10319851">Merienne et al. (1999)</a> identified a missense mutation (<a href="#0010">300075.0010</a>) in the RPS6KA3 gene. Patients exhibited none of the facial, digital, or skeletal features or the abnormal posture or gait typical of Coffin-Lowry syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10319851" 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="#8" class="mim-tip-reference" title="Field, M., Tarpey, P., Boyle, J., Edkins, S., Goodship, J., Luo, Y., Moon, J., Teague, J., Stratton, M. R., Futreal, P. A., Wooster, R., Raymond, F. L., Turner, G. <strong>Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.</strong> Clin. Genet. 70: 509-515, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17100996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17100996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17100996[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/10.1111/j.1399-0004.2006.00723.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17100996">Field et al. (2006)</a> identified 3 different mutations in the RPS6KA3 gene (see, e.g., <a href="#0020">300075.0020</a>-<a href="#0021">300075.0021</a>) in affected members of 3 unrelated families with nonsyndromic X-linked mental retardation. The patients had some variable features reminiscent of Coffin-Lowry syndrome, such as coarse facial features, kyphoscoliosis, short stature, and some redundancy of palmar skin with horizontal creases, but these additional features were considered to be too mild or atypical for a diagnosis of CLS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17100996" 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>
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<p>The level of residual RPS6KA3 activity seems to be related to the severity of the phenotype. <a href="#21" class="mim-tip-reference" title="Merienne, K., Jacquot, S., Pannetier, S., Zeniou, M., Bankier, A., Gecz, J., Mandel, J.-L., Mulley, J., Sassone-Corsi, P., Hanauer, A. <strong>A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation. (Letter)</strong> Nature Genet. 22: 13-14, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10319851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10319851</a>] [<a href="https://doi.org/10.1038/8719" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10319851">Merienne et al. (1999)</a> demonstrated 10 to 20% residual enzymatic activity in patients with nonsyndromic MRX19, which was postulated to result in the relatively mild phenotype without skeletal anomalies (<a href="#0010">300075.0010</a>). The patients reported by <a href="#8" class="mim-tip-reference" title="Field, M., Tarpey, P., Boyle, J., Edkins, S., Goodship, J., Luo, Y., Moon, J., Teague, J., Stratton, M. R., Futreal, P. A., Wooster, R., Raymond, F. L., Turner, G. <strong>Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.</strong> Clin. Genet. 70: 509-515, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17100996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17100996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17100996[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/10.1111/j.1399-0004.2006.00723.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17100996">Field et al. (2006)</a> with nonsyndromic X-linked mental retardation also had a milder phenotype, which the authors thought likely resulted from residual protein activity. <a href="#8" class="mim-tip-reference" title="Field, M., Tarpey, P., Boyle, J., Edkins, S., Goodship, J., Luo, Y., Moon, J., Teague, J., Stratton, M. R., Futreal, P. A., Wooster, R., Raymond, F. L., Turner, G. <strong>Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.</strong> Clin. Genet. 70: 509-515, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17100996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17100996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17100996[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/10.1111/j.1399-0004.2006.00723.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17100996">Field et al. (2006)</a> noted that the mutations in their report and the mutation (<a href="#0011">300075.0011</a>) reported by <a href="#14" class="mim-tip-reference" title="Manouvrier-Hanu, S., Amiel, J., Jacquot, S., Merienne, K., Moerman, A., Coeslier, A., Labarriere, F., Vallee, L., Croquette, M. F., Hanauer, A. <strong>Unreported RSK2 missense mutation in two male sibs with an unusually mild form of Coffin-Lowry syndrome.</strong> J. Med. Genet. 36: 775-778, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10528858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10528858</a>] [<a href="https://doi.org/10.1136/jmg.36.10.775" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10528858">Manouvrier-Hanu et al. (1999)</a> in a family with mild Coffin-Lowry syndrome were small in-frame deletions or missense mutations affecting the serine/threonine kinase domain. <a href="#8" class="mim-tip-reference" title="Field, M., Tarpey, P., Boyle, J., Edkins, S., Goodship, J., Luo, Y., Moon, J., Teague, J., Stratton, M. R., Futreal, P. A., Wooster, R., Raymond, F. L., Turner, G. <strong>Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.</strong> Clin. Genet. 70: 509-515, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17100996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17100996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17100996[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/10.1111/j.1399-0004.2006.00723.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17100996">Field et al. (2006)</a> hypothesized that the presence of a small amount of residual enzymatic activity may be sufficient to maintain normal osteoblast differentiation and ameliorate the skeletal phenotype associated with CLS. The level of residual enzymatic activity has also been linked to cognitive performance, with higher levels being associated with a higher level of intellectual function (<a href="#10" class="mim-tip-reference" title="Harum, K. H., Alemi, L., Johnston, M. V. <strong>Cognitive impairment in Coffin-Lowry syndrome correlates with reduced RSK2 activation.</strong> Neurology 56: 207-214, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11160957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11160957</a>] [<a href="https://doi.org/10.1212/wnl.56.2.207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11160957">Harum et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17100996+11160957+10319851+10528858" 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>
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<p>Using Rsk2 -/- mice, <a href="#29" class="mim-tip-reference" title="Yang, X., Matsuda, K., Bialek, P., Jacquot, S., Masuoka, H. C., Schinke, T., Li, L., Brancorsini, S., Sassone-Corsi, P., Townes, T. M., Hanauer, A., Karsenty, G. <strong>ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology: implication for Coffin-Lowry Syndrome.</strong> Cell 117: 387-398, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15109498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15109498</a>] [<a href="https://doi.org/10.1016/s0092-8674(04)00344-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15109498">Yang et al. (2004)</a> showed that RSK2 is required for osteoblast differentiation and function. They identified the transcription factor ATF4 (<a href="/entry/604064">604064</a>) as a critical substrate of RSK2 that is required for the timely onset of osteoblast differentiation, for terminal differentiation of osteoblasts, and for osteoblast-specific gene expression. Additionally, RSK2 and ATF4 were found to posttranscriptionally regulate the synthesis of type I collagen (see <a href="/entry/120150">120150</a>), the main constituent of the bone matrix. Accordingly, Atf4 deficiency in mice resulted in delayed bone formation during embryonic development and low bone mass throughout postnatal life. <a href="#29" class="mim-tip-reference" title="Yang, X., Matsuda, K., Bialek, P., Jacquot, S., Masuoka, H. C., Schinke, T., Li, L., Brancorsini, S., Sassone-Corsi, P., Townes, T. M., Hanauer, A., Karsenty, G. <strong>ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology: implication for Coffin-Lowry Syndrome.</strong> Cell 117: 387-398, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15109498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15109498</a>] [<a href="https://doi.org/10.1016/s0092-8674(04)00344-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15109498">Yang et al. (2004)</a> concluded that ATF4 is a critical regulator of osteoblast differentiation and function and that lack of ATF4 phosphorylation by RSK2 may contribute to the skeletal phenotype of Coffin-Lowry syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15109498" 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="David, J.-P., Mehic, D., Bakiri, L., Schilling, A. F., Mandic, V., Priemel, M., Idarraga, M. H., Reschke, M. O., Hoffmann, O., Amling, M., Wagner, E. F. <strong>Essential role of RSK2 in c-Fos-dependent osteosarcoma development.</strong> J. Clin. Invest. 115: 664-672, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15719069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15719069</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15719069[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/10.1172/JCI22877" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15719069">David et al. (2005)</a> demonstrated that Rsk2-null mice develop progressive osteopenia due to impaired osteoblast function and normal osteoclast differentiation. They also observed that c-fos (<a href="/entry/164810">164810</a>)-dependent osteosarcoma formation was impaired in the absence of Rsk2; the lack of c-fos phosphorylation led to reduced c-fos protein levels, which were thought to be responsible for the observed decreased proliferation and increased apoptosis of transformed osteoblasts. <a href="#3" class="mim-tip-reference" title="David, J.-P., Mehic, D., Bakiri, L., Schilling, A. F., Mandic, V., Priemel, M., Idarraga, M. H., Reschke, M. O., Hoffmann, O., Amling, M., Wagner, E. F. <strong>Essential role of RSK2 in c-Fos-dependent osteosarcoma development.</strong> J. Clin. Invest. 115: 664-672, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15719069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15719069</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15719069[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/10.1172/JCI22877" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15719069">David et al. (2005)</a> concluded that Rsk2-dependent stabilization of c-fos is essential for osteosarcoma formation in mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15719069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Poirier, R., Jacquot, S., Vaillend, C., Soutthiphong, A. A., Libbey, M., Davis, S., Laroche, S., Hanauer, A., Welzl, H., Lipp, H.-P., Wolfer, D. P. <strong>Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior.</strong> Behav. Genet. 37: 31-50, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033934</a>] [<a href="https://doi.org/10.1007/s10519-006-9116-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033934">Poirier et al. (2007)</a> found that Rsk2-null mice showed a mild impairment in spatial working memory, delayed acquisition of a spatial reference memory task, and long-term spatial memory deficits. In contrast, associative and recognition memory, as well as the habituation of exploratory activity were normal. The studies also revealed mild signs of disinhibition in exploratory activity, as well as a difficulty to adapt to new test environments, which likely contributed to the learning impairments displayed by Rsk2-null mice. There were no obvious brain abnormalities at the anatomic and histologic level. The behavioral changes observed supported a role for Rsk2 in cognitive functions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033934" 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="#15" class="mim-tip-reference" title="Marques Pereira, P., Gruss, M., Braun, K., Foos, N., Pannetier, S., Hanauer, A. <strong>Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin-Lowry syndrome.</strong> J. Neurochem. 107: 1325-1334, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18823370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18823370</a>] [<a href="https://doi.org/10.1111/j.1471-4159.2008.05703.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18823370">Marques Pereira et al. (2008)</a> found that Rsk2-null mice had increased cortical dopamine levels and overexpression of the DRD2 receptor (<a href="/entry/126450">126450</a>) and dopamine transporter (SLC6A3; <a href="/entry/126455">126455</a>). Evidence also suggested that the dopaminergic dysregulation may have been caused, at least in part, by increased tyrosine hydroxylase (TH; <a href="/entry/191290">191290</a>) hyperactivity. The authors suggested that these neurotransmitters changes may explain some of the cognitive alterations in Rsk2-null mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18823370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using microarray analysis, <a href="#20" class="mim-tip-reference" title="Mehmood, T., Schneider, A., Sibille, J., Pereira, P. M., Pannetier, S., Ammar, M. R., Dembele, D., Thibault-Carpentier, C., Rouach, N., Hanauer, A. <strong>Transcriptome profile reveals AMPA receptor dysfunction in the hippocampus of the Rsk2-knockout mice, an animal model of Coffin-Lowry syndrome.</strong> Hum. Genet. 129: 255-269, 2011. Note: Erratum: Hum. Genet. 129: 271 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21116650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21116650</a>] [<a href="https://doi.org/10.1007/s00439-010-0918-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21116650">Mehmood et al. (2011)</a> identified 100 genes that were differentially expressed in Rsk2 -/- mice compared with wildtype, and they confirmed differential expression of 24 of these genes using quantitative RT-PCR. Genes that were affected by Rsk2 deletion had roles in cell differentiation, proliferation, apoptosis, cell cycle, free radical scavenging, and nervous system development and function. <a href="#20" class="mim-tip-reference" title="Mehmood, T., Schneider, A., Sibille, J., Pereira, P. M., Pannetier, S., Ammar, M. R., Dembele, D., Thibault-Carpentier, C., Rouach, N., Hanauer, A. <strong>Transcriptome profile reveals AMPA receptor dysfunction in the hippocampus of the Rsk2-knockout mice, an animal model of Coffin-Lowry syndrome.</strong> Hum. Genet. 129: 255-269, 2011. Note: Erratum: Hum. Genet. 129: 271 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21116650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21116650</a>] [<a href="https://doi.org/10.1007/s00439-010-0918-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21116650">Mehmood et al. (2011)</a> characterized the consequences of 2-fold upregulation of the Gria2 gene (<a href="/entry/138247">138247</a>), which encodes a subunit of the AMPA glutamate receptor. Immunohistochemical analysis revealed significantly increased surface expression of Gria2 protein in Rsk2 -/- neurons. However, patch-clamp analysis showed significantly decreased basal AMPA receptor-mediated transmission in Rsk2 -/- hippocampal neurons. These changes in Gria2 protein expression and function appeared to be due to altered Gria2 mRNA editing and splicing in Rsk2 -/- mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21116650" 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>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>22 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300075[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>
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<p>Of 76 families segregating for CLS (<a href="/entry/303600">303600</a>), <a href="#27" class="mim-tip-reference" title="Trivier, E., De Cesare, D., Jacquot, S., Pannetier, S., Zackai, E., Young, I., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A. <strong>Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.</strong> Nature 384: 567-570, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8955270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8955270</a>] [<a href="https://doi.org/10.1038/384567a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8955270">Trivier et al. (1996)</a> identified one in which affected members had an approximately 2-kb deletion of the RPS6KA3 gene. By RT-PCR followed by direct sequencing, they demonstrated a deletion of 187 bp between nucleotides 406 and 593. The deletion produced a frameshift, generating a TAA termination codon 33 bp downstream of the deletion junction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8955270" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122454124 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122454124;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=rs122454124" 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=rs122454124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012417" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012417" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012417</a>
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<p>In a patient with CLS (<a href="/entry/303600">303600</a>), <a href="#27" class="mim-tip-reference" title="Trivier, E., De Cesare, D., Jacquot, S., Pannetier, S., Zackai, E., Young, I., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A. <strong>Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.</strong> Nature 384: 567-570, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8955270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8955270</a>] [<a href="https://doi.org/10.1038/384567a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8955270">Trivier et al. (1996)</a> demonstrated a G-to-T transition at nucleotide 224 in the RSK2 gene, resulting in a gly75-to-val substitution. Gly75 is a conserved residue located within the putative ATP-binding site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8955270" 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>
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RPS6KA3, SER227ALA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122454125 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122454125;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=rs122454125" 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=rs122454125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012418" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012418" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012418</a>
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<p>In a patient with CLS (<a href="/entry/303600">303600</a>), <a href="#27" class="mim-tip-reference" title="Trivier, E., De Cesare, D., Jacquot, S., Pannetier, S., Zackai, E., Young, I., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A. <strong>Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.</strong> Nature 384: 567-570, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8955270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8955270</a>] [<a href="https://doi.org/10.1038/384567a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8955270">Trivier et al. (1996)</a> demonstrated a T-to-G transition at nucleotide 679 in the RSK2 gene, resulting in a ser227-to-ala substitution. Ser227 is a conserved residue, and is believed to be a phosphorylation site of the kinase domain of the N terminus, which is essential for catalytic function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8955270" 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>
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<strong>.0004 COFFIN-LOWRY SYNDROME</strong>
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RPS6KA3, VAL82PHE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122454126 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122454126;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=rs122454126" 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=rs122454126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012419" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012419" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012419</a>
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<p>In a familial case of CLS (<a href="/entry/303600">303600</a>), <a href="#11" class="mim-tip-reference" title="Jacquot, S., Merienne, K., De Cesare, D., Pannetier, S., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A. <strong>Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations.</strong> Am. J. Hum. Genet. 63: 1631-1640, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837815</a>] [<a href="https://doi.org/10.1086/302153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837815">Jacquot et al. (1998)</a> found a 244G-T transversion in exon 4, resulting in a val82-to-phe amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837815" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776755 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776755;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=rs587776755" 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=rs587776755" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012420" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012420" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012420</a>
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<p><a href="#12" class="mim-tip-reference" title="Jacquot, S., Merienne, K., Pannetier, S., Blumenfeld, S., Schinzel, A., Hanauer, A. <strong>Germline mosaicism in Coffin-Lowry syndrome.</strong> Europ. J. Hum. Genet. 6: 578-582, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887375</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200230" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887375">Jacquot et al. (1998)</a> identified a Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>) pedigree in which the disorder was associated with a novel splice site mutation in the RSK2 gene, leading to in-frame skipping of exon 5: a G-to-C transition in the splice acceptor site (position -1) immediately upstream of exon 5. Western blot analysis, using an antibody directed against the C terminus of the RSK2 protein, failed to reveal RSK2 protein in this patient, suggesting strongly that the internally deleted protein was unstable. The mutation was present in the DNA of 1 affected son and 1 manifesting daughter but was absent in 2 asymptomatic daughters, who carried the at-risk haplotype, and in the mother's somatic cell (lymphocyte) DNA. The results were considered consistent with the mutation having arisen as a postzygotic event in the mother, who therefore was a germinal mosaic. The mother was clinically normal but, in addition to strong wildtype bands shown on SSCP analysis, there were very faint bands corresponding to a small proportion (less than 1%) of mutated DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887375" 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>
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<strong>.0006 COFFIN-LOWRY SYNDROME</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122454127 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122454127;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=rs122454127" 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=rs122454127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012421" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012421" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012421</a>
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<p>In 2 unrelated African American patients with CLS (<a href="/entry/303600">303600</a>), <a href="#1" class="mim-tip-reference" title="Abidi, F., Jacquot, S., Lassiter, C., Trivier, E., Hanauer, A., Schwartz, C. E. <strong>Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).</strong> Europ. J. Hum. Genet. 7: 20-26, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094187</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094187">Abidi et al. (1999)</a> observed an arg114-to-trp missense mutation resulting from a 340C-T nucleotide change in the RSK2 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094187" 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>
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<strong>.0007 COFFIN-LOWRY SYNDROME</strong>
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RPS6KA3, 2-BP DEL, 451AG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1603426295 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1603426295;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=rs1603426295" 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=rs1603426295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012422 OR RCV004760327" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012422, RCV004760327" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012422...</a>
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<p>In a patient with CLS (<a href="/entry/303600">303600</a>), <a href="#1" class="mim-tip-reference" title="Abidi, F., Jacquot, S., Lassiter, C., Trivier, E., Hanauer, A., Schwartz, C. E. <strong>Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).</strong> Europ. J. Hum. Genet. 7: 20-26, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094187</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094187">Abidi et al. (1999)</a> found that the RSK2 gene contained a 2-bp deletion of bases 451A and 452G, causing a frameshift that resulted in a stop codon 25 amino acids downstream and thereby producing a truncated protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094187" 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>
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<strong>.0008 COFFIN-LOWRY SYNDROME</strong>
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RPS6KA3, GLN689TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122454128 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122454128;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=rs122454128" 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=rs122454128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012423" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012423" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012423</a>
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<p>In an African American patient with CLS (<a href="/entry/303600">303600</a>), <a href="#1" class="mim-tip-reference" title="Abidi, F., Jacquot, S., Lassiter, C., Trivier, E., Hanauer, A., Schwartz, C. E. <strong>Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).</strong> Europ. J. Hum. Genet. 7: 20-26, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094187</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094187">Abidi et al. (1999)</a> found a 2065C-T transition that gave rise to a premature stop codon (gln689 to ter), and a truncated protein lacking the last 51 amino acids of the RSK2 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094187" 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>
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<span class="mim-font">
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<strong>.0009 COFFIN-LOWRY SYNDROME</strong>
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RPS6KA3, ARG729GLN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28935171 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28935171;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=rs28935171" 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=rs28935171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012424 OR RCV000413967 OR RCV001257622 OR RCV001266366" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012424, RCV000413967, RCV001257622, RCV001266366" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012424...</a>
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<p>In a patient with CLS (<a href="/entry/303600">303600</a>), <a href="#1" class="mim-tip-reference" title="Abidi, F., Jacquot, S., Lassiter, C., Trivier, E., Hanauer, A., Schwartz, C. E. <strong>Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).</strong> Europ. J. Hum. Genet. 7: 20-26, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094187</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094187">Abidi et al. (1999)</a> found a 2186G-A nucleotide change in the RSK2 gene, resulting in an arg729-to-gln missense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094187" 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>
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<a id="0010" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0010 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 19</strong>
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RPS6KA3, ARG383TRP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122454129 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122454129;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=rs122454129" 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=rs122454129" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012425" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012425" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012425</a>
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</span>
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<span class="mim-text-font">
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<p>In affected members of a family with nonsyndromic X-linked intellectual developmental disorder-19 (XLID19; <a href="/entry/300844">300844</a>), <a href="#21" class="mim-tip-reference" title="Merienne, K., Jacquot, S., Pannetier, S., Zeniou, M., Bankier, A., Gecz, J., Mandel, J.-L., Mulley, J., Sassone-Corsi, P., Hanauer, A. <strong>A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation. (Letter)</strong> Nature Genet. 22: 13-14, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10319851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10319851</a>] [<a href="https://doi.org/10.1038/8719" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10319851">Merienne et al. (1999)</a> identified a 1147C-T transition in exon 14 of the RPS6KA3 gene, resulting in an arg383-to-trp (R383W) substitution. This mutation occurred in a CpG dinucleotide motif. Reexamination of 2 of the affected individuals, then 38 and 29 years old, showed that they exhibited none of the facial, digital, or skeletal features or the abnormal posture or gait typical of Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>). Furthermore, both presented with very mild mental retardation, compatible with social autonomy. It had previously been found that most CLS-producing mutations inactivate RPS6KA3. The mutation in the family reported by <a href="#21" class="mim-tip-reference" title="Merienne, K., Jacquot, S., Pannetier, S., Zeniou, M., Bankier, A., Gecz, J., Mandel, J.-L., Mulley, J., Sassone-Corsi, P., Hanauer, A. <strong>A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation. (Letter)</strong> Nature Genet. 22: 13-14, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10319851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10319851</a>] [<a href="https://doi.org/10.1038/8719" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10319851">Merienne et al. (1999)</a> was notable in that the 5- to 6-fold decrease in kinase activity resulted in a mild phenotype. This demonstrated that 15 to 20% of RPS6KA3 activity is sufficient for normal signaling of the MAPK-RPS6KA3 pathway involved in skeletal development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10319851" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122454130 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122454130;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=rs122454130" 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=rs122454130" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012426" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012426" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012426</a>
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<p><a href="#14" class="mim-tip-reference" title="Manouvrier-Hanu, S., Amiel, J., Jacquot, S., Merienne, K., Moerman, A., Coeslier, A., Labarriere, F., Vallee, L., Croquette, M. F., Hanauer, A. <strong>Unreported RSK2 missense mutation in two male sibs with an unusually mild form of Coffin-Lowry syndrome.</strong> J. Med. Genet. 36: 775-778, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10528858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10528858</a>] [<a href="https://doi.org/10.1136/jmg.36.10.775" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10528858">Manouvrier-Hanu et al. (1999)</a> reported 2 male sibs with a mild form of CLS (<a href="/entry/303600">303600</a>) who had a T-to-A transversion in exon 7 of the RPS6KA3 gene leading to the substitution of a lysine residue in place of an isoleucine residue at position 189 (I189K). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10528858" 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>
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<strong>.0012 COFFIN-LOWRY SYNDROME</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1603426293 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1603426293;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=rs1603426293" 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=rs1603426293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012427" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012427" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012427</a>
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<p>In a patient with Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>), <a href="#31" class="mim-tip-reference" title="Zeniou, M., Pannetier, S., Fryns, J.-P., Hanauer, A. <strong>Unusual splice-site mutations in the RSK2 gene and suggestion of genetic heterogeneity in Coffin-Lowry syndrome.</strong> Am. J. Hum. Genet. 70: 1421-1433, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992250</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992250[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/10.1086/340607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11992250">Zeniou et al. (2002)</a> identified an IVS6+3A-G intronic mutation of the RPS6KA3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11992250" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555943503 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555943503;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=rs1555943503" 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=rs1555943503" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000623700 OR RCV001798931 OR RCV004702205" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000623700, RCV001798931, RCV004702205" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000623700...</a>
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<p>In a patient with Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>), <a href="#31" class="mim-tip-reference" title="Zeniou, M., Pannetier, S., Fryns, J.-P., Hanauer, A. <strong>Unusual splice-site mutations in the RSK2 gene and suggestion of genetic heterogeneity in Coffin-Lowry syndrome.</strong> Am. J. Hum. Genet. 70: 1421-1433, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992250</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992250[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/10.1086/340607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11992250">Zeniou et al. (2002)</a> identified an IVS5-11A-G intronic mutation of the RPS6KA3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11992250" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1603417213 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1603417213;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=rs1603417213" 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=rs1603417213" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012429" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012429" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012429</a>
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<p>In a male infant native to the Cook Islands with Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>), <a href="#19" class="mim-tip-reference" title="McGaughran, J., Delaunoy, J.-P. <strong>Coffin-Lowry syndrome in a patient from the Cook Islands confirmed by the presence of a unique mutation. (Letter)</strong> Am. J. Med. Genet. 113: 309-311, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12439904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12439904</a>] [<a href="https://doi.org/10.1002/ajmg.10786" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12439904">McGaughran and Delaunoy (2002)</a> identified a 1-bp deletion (2144delC) in the RPS6KA3 gene, resulting in a stop codon 21 amino acids before the normal termination codon. The proband was the sixth child of nonconsanguineous parents; the fifth child, also male, died at age 7 months, presumably of the same condition. The proband's inner canthal distance was greater than the 97th centile. He had large anterior and posterior fontanels, mild synophrys, and a long philtrum. His fingers were flattened and tapering. His mother's fingers had a similar but more marked appearance. Her facial appearance was consistent with the diagnosis of heterozygous carrier of CLS, but she did not undergo molecular testing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12439904" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2148664125 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2148664125;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=rs2148664125" 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=rs2148664125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012430" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012430" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012430</a>
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<p><a href="#9" class="mim-tip-reference" title="Fryssira, H., Kountoupi, S., Delaunoy, J. P., Thomaidis, L. <strong>A female with Coffin-Lowry syndrome and 'cataplexy'.</strong> Genet. Counsel. 13: 405-409, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12558110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12558110</a>]" pmid="12558110">Fryssira et al. (2002)</a> described a female patient with full-blown CLS (<a href="/entry/303600">303600</a>), manifested by facial dysmorphism, tapering fingers, and skeletal deformities (pectus excavatum and kyphoscoliosis), who was found to have an A-to-G transition in the RSK2 gene, creating a suppression of the splicing site between intron 12 and exon 13. Her overall IQ was 53. At the age of 9 years, there was onset of a cataplexy-like phenomenon characterized by a sudden and reversible loss of muscle tone without loss of consciousness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12558110" 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>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012431" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012431" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012431</a>
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<p>In a patient with Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>), <a href="#18" class="mim-tip-reference" title="Martinez-Garay, I., Ballesta, M. J., Oltra, S., Orellana, C., Palomeque, A., Molto, M. D., Prieto, F., Martinez, F. <strong>Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing Coffin-Lowry syndrome.</strong> Clin. Genet. 64: 491-496, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14986828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14986828</a>] [<a href="https://doi.org/10.1046/j.1399-0004.2003.00166.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14986828">Martinez-Garay et al. (2003)</a> identified a de novo insertion of a 5-prime truncated LINE-1 element at position -8 of intron 3 of the RPS6KA3, which led to skipping of exon 4, a shift of the reading frame, and a premature stop codon. The 2,800-bp L1 fragment showed a rearrangement with a small deletion and a partial inversion of ORF2, flanked by short direct repeats that duplicated the acceptor splice site. A cDNA analysis showed that both sites were apparently nonfunctional. The 30-year-old patient had mental retardation, hypotonia, sensorineural hearing deficit, downslanting palpebral fissures, broad nose, anteverted nares, large mouth, thick everted lips, large and everted ears, pectus carinatum, tapering fingers with drumstick terminal phalanges, forearm fullness, and flat feet. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14986828" 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>
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<strong>.0017 COFFIN-LOWRY SYNDROME</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122454131 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122454131;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=rs122454131" 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=rs122454131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012432" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012432" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012432</a>
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<p>In monozygotic twins with Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>) and in their mother, who was mildly affected, <a href="#18" class="mim-tip-reference" title="Martinez-Garay, I., Ballesta, M. J., Oltra, S., Orellana, C., Palomeque, A., Molto, M. D., Prieto, F., Martinez, F. <strong>Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing Coffin-Lowry syndrome.</strong> Clin. Genet. 64: 491-496, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14986828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14986828</a>] [<a href="https://doi.org/10.1046/j.1399-0004.2003.00166.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14986828">Martinez-Garay et al. (2003)</a> identified an 803T-C transition in exon 10 of the RPS6KA3 gene, which resulted in a phe268-to-ser (F268S) substitution. The mother showed tapering fingers, obesity, large mouth, and large and dysplastic ears. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14986828" 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>
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<strong>.0018 COFFIN-LOWRY SYNDROME</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1603420690 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1603420690;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=rs1603420690" 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=rs1603420690" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012433" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012433" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012433</a>
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<p>In a 14-year-old boy with physical and developmental findings consistent with Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>), <a href="#7" class="mim-tip-reference" title="Facher, J. J., Regier, E. J., Jacobs, G. H., Siwik, E., Delaunoy, J.-P., Robin, N. H. <strong>Cardiomyopathy in Coffin-Lowry syndrome.</strong> Am. J. Med. Genet. 128A: 176-178, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15214012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15214012</a>] [<a href="https://doi.org/10.1002/ajmg.a.30056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15214012">Facher et al. (2004)</a> identified a 3-bp deletion (TAT) at position 1428 of the RPS6KA3 gene, resulting in the loss of an isoleucine. The patient was unusual in that he had restrictive cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15214012" 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>
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<strong>.0019 COFFIN-LOWRY SYNDROME</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012434" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012434" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012434</a>
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<p>In an 1.5-year-old boy with Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>), <a href="#16" class="mim-tip-reference" title="Marques Pereira, P., Heron, D., Hanauer, A. <strong>The first large duplication of the RSK2 gene identified in a Coffin-Lowry syndrome patient.</strong> Hum. Genet. 122: 541-543, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17717706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17717706</a>] [<a href="https://doi.org/10.1007/s00439-007-0424-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17717706">Marques Pereira et al. (2007)</a> identified an in-frame tandem duplication of exons 17 to 20, resulting from insertion of 516 nucleotides at nucleotide 1959, that arose from a homologous unequal recombination between Alu sequences. In vitro kinase assay showed that mutant RSK2 was inactive. The patient's mother, who had childhood scoliosis and difficulties in school, was found to carry the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17717706" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs398122813 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122813;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=rs398122813" 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=rs398122813" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000022822" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022822" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022822</a>
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<p>In affected members of a family with nonsyndromic X-linked intellectual developmental disorder-19 (XLID19; <a href="/entry/300844">300844</a>), <a href="#8" class="mim-tip-reference" title="Field, M., Tarpey, P., Boyle, J., Edkins, S., Goodship, J., Luo, Y., Moon, J., Teague, J., Stratton, M. R., Futreal, P. A., Wooster, R., Raymond, F. L., Turner, G. <strong>Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.</strong> Clin. Genet. 70: 509-515, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17100996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17100996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17100996[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/10.1111/j.1399-0004.2006.00723.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17100996">Field et al. (2006)</a> identified an in-frame 3-bp deletion (454delGGA) in the RPS6KA3 gene, resulting in the deletion of gly152. This residue is highly conserved and located in the serine/threonine protein kinase domain. The patients had coarse facial features, kyphoscoliosis, and some redundancy of palmar skin with horizontal creases, but no digital tapering or short stature. These additional features were considered to be too mild for a diagnosis of Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>). <a href="#8" class="mim-tip-reference" title="Field, M., Tarpey, P., Boyle, J., Edkins, S., Goodship, J., Luo, Y., Moon, J., Teague, J., Stratton, M. R., Futreal, P. A., Wooster, R., Raymond, F. L., Turner, G. <strong>Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.</strong> Clin. Genet. 70: 509-515, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17100996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17100996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17100996[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/10.1111/j.1399-0004.2006.00723.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17100996">Field et al. (2006)</a> hypothesized that the mutant protein had a small amount of residual activity, which likely explained the relatively mild phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17100996" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906703 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906703;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=rs387906703" 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=rs387906703" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000022823" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022823" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022823</a>
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<p>In 3 brothers with nonsyndromic X-linked intellectual developmental disorder-19 (XLID19; <a href="/entry/300844">300844</a>), <a href="#8" class="mim-tip-reference" title="Field, M., Tarpey, P., Boyle, J., Edkins, S., Goodship, J., Luo, Y., Moon, J., Teague, J., Stratton, M. R., Futreal, P. A., Wooster, R., Raymond, F. L., Turner, G. <strong>Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.</strong> Clin. Genet. 70: 509-515, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17100996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17100996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17100996[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/10.1111/j.1399-0004.2006.00723.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17100996">Field et al. (2006)</a> identified a 343A-T transversion in the RPS6KA3 gene, resulting in a thr115-to-ser (T115S) substitution in a highly conserved region in the serine/threonine protein kinase domain. The patients had short stature, hypertelorism, and a slightly full lower lip, but these features were considered to be too subtle for a diagnosis of Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>). <a href="#8" class="mim-tip-reference" title="Field, M., Tarpey, P., Boyle, J., Edkins, S., Goodship, J., Luo, Y., Moon, J., Teague, J., Stratton, M. R., Futreal, P. A., Wooster, R., Raymond, F. L., Turner, G. <strong>Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.</strong> Clin. Genet. 70: 509-515, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17100996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17100996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17100996[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/10.1111/j.1399-0004.2006.00723.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17100996">Field et al. (2006)</a> hypothesized that the mutant protein had a small amount of residual activity, which likely explained the relatively mild phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17100996" 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>
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<strong>.0022 COFFIN-LOWRY SYNDROME</strong>
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RPS6KA3, 7.2-KB DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000170489" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170489" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170489</a>
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<p>In cells derived from an affected member of the original family with Coffin-Lowry syndrome (CLS; <a href="/entry/303600">303600</a>) reported by <a href="#13" class="mim-tip-reference" title="Lowry, R. B., Miller, J. R., Fraser, F. C. <strong>A new dominant gene mental retardation syndrome: associated with small stature, tapering fingers, characteristic facies, and possible hydrocephalus.</strong> Am. J. Dis. Child. 121: 496-500, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5581017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5581017</a>]" pmid="5581017">Lowry et al. (1971)</a>, <a href="#23" class="mim-tip-reference" title="Nishimoto, H. K., Ha, K., Jones, J. R., Dwivedi, A., Cho, H.-M., Layman, L. C., Kim, H.-G. <strong>The historical Coffin-Lowry syndrome family revisited: identification of two novel mutations of RPS6KA3 in three male patients.</strong> Am. J. Med. Genet. 164A: 2172-2179, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25044551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25044551</a>] [<a href="https://doi.org/10.1002/ajmg.a.36488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25044551">Nishimoto et al. (2014)</a> identified an in-frame deletion of exons 15 and 16 (r.1228_1443del216) in the RPS6KA3 gene, resulting in the deletion of 72 amino acids from 410 to 418 in the C-terminal kinase domain, predicting the loss of function of this domain. Microarray analysis indicated that the maximum size of the deletion was about 7.2 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25044551+5581017" 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>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>REFERENCES</strong>
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<strong>Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).</strong>
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[<a href="https://doi.org/10.1038/sj.ejhg.5200231" target="_blank">Full Text</a>]
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<strong>Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients.</strong>
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[<a href="https://doi.org/10.2337/diab.44.1.90" target="_blank">Full Text</a>]
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David, J.-P., Mehic, D., Bakiri, L., Schilling, A. F., Mandic, V., Priemel, M., Idarraga, M. H., Reschke, M. O., Hoffmann, O., Amling, M., Wagner, E. F.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15719069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15719069</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15719069[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=15719069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI22877" target="_blank">Full Text</a>]
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Delaunoy, J. P., Dubos, A., Marques Pereira, P., Hanauer, A.
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<strong>Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome.</strong>
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Clin. Genet. 70: 161-166, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16879200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16879200</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16879200" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2006.00660.x" target="_blank">Full Text</a>]
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Delaunoy, J.-P., Abidi, F., Zeniou, M., Jacquot, S., Merienne, K., Pannetier, S., Schmitt, M., Schwartz, C. E., Hanauer, A.
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<strong>Mutations in the X-linked RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome.</strong>
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Hum. Mutat. 17: 103-116, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11180593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11180593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11180593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/1098-1004(200102)17:2<103::AID-HUMU2>3.0.CO;2-N" target="_blank">Full Text</a>]
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Dent, P., Lavoinne, A., Nekielny, S., Caudwell, F. B., Watt, P., Cohen, P.
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<strong>The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle.</strong>
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Nature 348: 302-308, 1990.
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[<a href="https://doi.org/10.1038/348302a0" target="_blank">Full Text</a>]
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Facher, J. J., Regier, E. J., Jacobs, G. H., Siwik, E., Delaunoy, J.-P., Robin, N. H.
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<strong>Cardiomyopathy in Coffin-Lowry syndrome.</strong>
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[<a href="https://doi.org/10.1002/ajmg.a.30056" target="_blank">Full Text</a>]
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<a id="Field2006" class="mim-anchor"></a>
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Field, M., Tarpey, P., Boyle, J., Edkins, S., Goodship, J., Luo, Y., Moon, J., Teague, J., Stratton, M. R., Futreal, P. A., Wooster, R., Raymond, F. L., Turner, G.
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<strong>Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.</strong>
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Clin. Genet. 70: 509-515, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17100996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17100996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17100996[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=17100996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2006.00723.x" target="_blank">Full Text</a>]
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Fryssira, H., Kountoupi, S., Delaunoy, J. P., Thomaidis, L.
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<strong>A female with Coffin-Lowry syndrome and 'cataplexy'.</strong>
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Genet. Counsel. 13: 405-409, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12558110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12558110</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12558110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Harum, K. H., Alemi, L., Johnston, M. V.
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<strong>Cognitive impairment in Coffin-Lowry syndrome correlates with reduced RSK2 activation.</strong>
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Neurology 56: 207-214, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11160957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11160957</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11160957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.56.2.207" target="_blank">Full Text</a>]
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Jacquot, S., Merienne, K., De Cesare, D., Pannetier, S., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A.
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<strong>Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20383198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20383198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20383198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/onc.2010.105" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="29" class="mim-anchor"></a>
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<a id="Yang2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Yang, X., Matsuda, K., Bialek, P., Jacquot, S., Masuoka, H. C., Schinke, T., Li, L., Brancorsini, S., Sassone-Corsi, P., Townes, T. M., Hanauer, A., Karsenty, G.
|
|
<strong>ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology: implication for Coffin-Lowry Syndrome.</strong>
|
|
Cell 117: 387-398, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15109498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15109498</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15109498" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0092-8674(04)00344-7" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="30" class="mim-anchor"></a>
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<a id="Zeniou2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Zeniou, M., Ding, T., Trivier, E., Hanauer, A.
|
|
<strong>Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning.</strong>
|
|
Hum. Molec. Genet. 11: 2929-2940, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393804</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/11.23.2929" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="31" class="mim-anchor"></a>
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<a id="Zeniou2002" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Zeniou, M., Pannetier, S., Fryns, J.-P., Hanauer, A.
|
|
<strong>Unusual splice-site mutations in the RSK2 gene and suggestion of genetic heterogeneity in Coffin-Lowry syndrome.</strong>
|
|
Am. J. Hum. Genet. 70: 1421-1433, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992250</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992250[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=11992250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/340607" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="32" class="mim-anchor"></a>
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<a id="Zhao1995" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Zhao, Y., Bjorbaek, C., Weremowicz, S., Morton, C. C., Moller, D. E.
|
|
<strong>RSK3 encodes a novel pp90rsk isoform with a unique N-terminal sequence: growth factor-stimulated kinase function and nuclear translocation.</strong>
|
|
Molec. Cell. Biol. 15: 4353-4363, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7623830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7623830</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7623830" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1128/MCB.15.8.4353" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="33" class="mim-anchor"></a>
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<a id="Zhou2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhou, W., Cao, H., Yang, X., Cong, K., Wang, W., Chen, T., Yin, H., Wu, Z., Cai, X., Liu, T., Xiao, J.
|
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<strong>Characterization of nuclear localization signal in the N terminus of integrin-linked kinase-associated phosphatase (ILKAP) and its essential role in the down-regulation of RSK2 protein signaling.</strong>
|
|
J. Biol. Chem. 288: 6259-6271, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23329845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23329845</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23329845[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=23329845" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M112.432195" target="_blank">Full Text</a>]
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</p>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 06/10/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<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">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 5/6/2015<br>Patricia A. Hartz - updated : 5/15/2013<br>Cassandra L. Kniffin - updated : 5/19/2011<br>Patricia A. Hartz - updated : 5/12/2011<br>Cassandra L. Kniffin - updated : 8/20/2010<br>Marla J. F. O'Neill - updated : 3/18/2008<br>Marla J. F. O'Neill - updated : 9/22/2006<br>Patricia A. Hartz - updated : 1/27/2006<br>Marla J. F. O'Neill - updated : 4/11/2005<br>Marla J. F. O'Neill - updated : 7/20/2004<br>Stylianos E. Antonarakis - updated : 6/9/2004<br>George E. Tiller - updated : 3/31/2004<br>Victor A. McKusick - updated : 1/12/2004<br>Victor A. McKusick - updated : 11/27/2002<br>Cassandra L. Kniffin - updated : 7/26/2002<br>Victor A. McKusick - updated : 6/11/2002<br>Victor A. McKusick - updated : 2/21/2001<br>Michael J. Wright - updated : 2/4/2000<br>Ada Hamosh - updated : 8/5/1999<br>Victor A. McKusick - updated : 4/27/1999<br>Victor A. McKusick - updated : 4/21/1999<br>Victor A. McKusick - updated : 3/17/1999<br>Victor A. McKusick - updated : 1/11/1999
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 2/14/1997
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/25/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<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">
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<span class="mim-text-font">
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carol : 08/20/2021<br>carol : 03/31/2021<br>mgross : 06/10/2020<br>carol : 05/19/2015<br>carol : 5/14/2015<br>mcolton : 5/13/2015<br>ckniffin : 5/6/2015<br>carol : 4/13/2015<br>carol : 12/20/2013<br>carol : 8/13/2013<br>mgross : 5/15/2013<br>mgross : 2/5/2013<br>terry : 4/9/2012<br>wwang : 6/7/2011<br>ckniffin : 5/19/2011<br>mgross : 5/17/2011<br>mgross : 5/17/2011<br>terry : 5/12/2011<br>terry : 11/24/2010<br>wwang : 8/24/2010<br>ckniffin : 8/20/2010<br>joanna : 7/27/2010<br>carol : 12/2/2008<br>wwang : 3/26/2008<br>terry : 3/18/2008<br>mgross : 3/13/2007<br>wwang : 9/22/2006<br>carol : 2/17/2006<br>mgross : 2/1/2006<br>terry : 1/27/2006<br>tkritzer : 4/11/2005<br>terry : 4/11/2005<br>tkritzer : 1/20/2005<br>carol : 7/21/2004<br>terry : 7/20/2004<br>mgross : 6/9/2004<br>tkritzer : 3/31/2004<br>tkritzer : 3/31/2004<br>carol : 1/20/2004<br>terry : 1/12/2004<br>alopez : 3/26/2003<br>carol : 3/4/2003<br>carol : 12/4/2002<br>carol : 12/4/2002<br>tkritzer : 12/3/2002<br>terry : 11/27/2002<br>carol : 8/9/2002<br>ckniffin : 8/9/2002<br>ckniffin : 7/26/2002<br>alopez : 6/13/2002<br>terry : 6/11/2002<br>mcapotos : 3/1/2001<br>mcapotos : 2/27/2001<br>terry : 2/21/2001<br>alopez : 2/4/2000<br>alopez : 2/4/2000<br>alopez : 8/5/1999<br>alopez : 4/29/1999<br>terry : 4/27/1999<br>carol : 4/23/1999<br>terry : 4/21/1999<br>carol : 3/26/1999<br>terry : 3/17/1999<br>carol : 1/18/1999<br>terry : 1/11/1999<br>carol : 12/8/1998<br>psherman : 11/16/1998<br>psherman : 9/4/1998<br>dkim : 7/30/1998<br>alopez : 10/3/1997<br>alopez : 7/3/1997<br>mark : 2/14/1997<br>mark : 2/14/1997<br>mark : 2/14/1997
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
|
<strong>*</strong> 300075
|
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<h3>
|
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<span class="mim-font">
|
|
|
|
RIBOSOMAL PROTEIN S6 KINASE A3; RPS6KA3
|
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|
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</span>
|
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</h3>
|
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</div>
|
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<div>
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<br />
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</div>
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<div>
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<div >
|
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
RIBOSOMAL PROTEIN S6 KINASE, 90-KD, 3<br />
|
|
RIBOSOMAL S6 KINASE 2; RSK2<br />
|
|
MITOGEN-ACTIVATED PROTEIN KINASE-ACTIVATED PROTEIN KINASE 1B; MAPKAPK1B<br />
|
|
MAPKAP KINASE 1B<br />
|
|
ISPK1
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: RPS6KA3</em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
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|
|
<strong>SNOMEDCT:</strong> 15182000;
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
|
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<em>
|
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Cytogenetic location: Xp22.12
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : X:20,149,911-20,267,097 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
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</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
Xp22.12
|
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</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Coffin-Lowry syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
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<span class="mim-font">
|
|
303600
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
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|
|
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|
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</tr>
|
|
|
|
|
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|
|
|
|
|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Intellectual developmental disorder, X-linked 19
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
300844
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
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</span>
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</h4>
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<span class="mim-text-font">
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<p>The RPS6KA3 gene encodes a member of the RSK (ribosomal S6 kinase) family of growth factor-regulated serine/threonine kinases, known also as p90(rsk). RSK proteins contain 2 functional kinase catalytic domains: the N-terminal kinase domain belongs to the AGC kinase family (see 188830), and the C-terminal kinase domain belongs to the CamK family (see 604998). The kinase domains are connected by a 100-amino acid linker region containing a PDK (PDPK1; 605213) docking site. RSK proteins are directly phosphorylated and activated by MAPK proteins (e.g., ERK1; 601795) in response to growth factors, polypeptide hormones, and neurotransmitters, and then subsequently phosphorylate many substrates. RSKs appear to have important roles in cell cycle progression, differentiation, and cell survival (review by Marques Pereira et al., 2010). </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Bjorbaek et al. (1995) showed that the cDNA encoding RPS6KA3, which they called ISPK1, encodes a predicted protein of 740 amino acids. </p><p>Zeniou et al. (2002) determined the expression of the RSK1 (RPS6KA1; 601684), RSK2, and RSK3 (RPS6KA2; 601685) genes in various human tissues, during mouse embryogenesis, and in mouse brain. The 3 RSK mRNAs were expressed in all human tissues and brain regions tested, supporting functional redundancy. However, tissue-specific variations in levels suggested that the proteins may also serve specific roles. The mouse Rsk3 gene was prominently expressed in the developing neural and sensory tissues, whereas Rsk1 gene expression was the strongest in various other tissues with high proliferative activity, suggesting distinct roles during development. In adult mouse brain, the highest levels of Rsk2 expression were observed in regions with high synaptic activity, including the neocortex, the hippocampus, and Purkinje cells. The authors suggested that in these areas, which are essential to cognitive function and learning, the RSK1 and RSK3 genes may not be able to fully compensate for a lack of RSK2 function. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Jacquot et al. (1998) found that the open reading frame of the RPS6KA3 coding region contains 22 exons. </p>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a study of the region of the X chromosome (Xp22.2) within which the Coffin-Lowry syndrome (CLS; 303600) maps, Trivier et al. (1996) identified an expressed sequence tag (EST) that showed 100% homology with a cDNA coding for RPS6KA3. Its localization was independently confirmed by Bjorbaek et al. (1995). </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>During the immediate-early response of mammalian cells to mitogens, histone H3 (see 602810) is rapidly and transiently phosphorylated by one or more kinases. Sassone-Corsi et al. (1999) demonstrated that RSK2 was required for epidermal growth factor (EGF; 131530)-stimulated phosphorylation of H3. Fibroblasts derived from a CLS patient failed to exhibit EGF-stimulated phosphorylation of H3, although H3 was phosphorylated during mitosis. Introduction of the wildtype RSK2 gene restored EGF-stimulated phosphorylation of H3 in the CLS cells. In addition, disruption of the RSK2 gene by homologous recombination in murine embryonic stem cells abolished EGF-stimulated phosphorylation of H3. H3 appears to be a direct or indirect target of RSK2, suggesting to Sassone-Corsi et al. (1999) that chromatin remodeling might contribute to mitogen-activated protein kinase-regulated gene expression. </p><p>Thomas et al. (2005) presented evidence suggesting that RSK2 is involved in regulation of excitatory AMPA receptor synaptic transmission by interacting with and phosphorylating PDZ domain-containing proteins. </p><p>Spindle assembly checkpoint (SAC) prevents anaphase onset until all chromosomes have successfully attached to spindle microtubules. Using Xenopus egg extracts and HeLa cells, Vigneron et al. (2010) found that RSK2 had a role in spindle assembly checkpoint. RSK2 localized to kinetochores during SAC. Immunofluorescence analysis and knockdown studies revealed that RSK2 and Aurora B (AURKB; 604970) depended upon each other for kinetochore localization. Association of RSK2 at kinetochores was required to maintain SAC activation and localization of MAD1 (MXD1; 600021), MAD2 (MAD2L1; 601467), and CENPE (117143) at kinetochores. Expression of Xenopus Rsk2 rescued the effects of RSK2 knockdown in HeLa cells. </p><p>Zhou et al. (2013) found that ILKAP (618909) interacted with RSK2 in the nucleus and inhibited its activity. Inhibition of RSK2 kinase activity induced apoptosis by reducing expression of the RSK2 downstream factor cyclin D1 (CCND1; 168461). </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</h4>
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<span class="mim-text-font">
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<p><strong><em>Coffin-Lowry Syndrome</em></strong></p><p>
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The localization of the RSK2 gene within the Coffin-Lowry syndrome (CLS; 303600) interval, together with its role in signaling pathways, prompted Trivier et al. (1996) to investigate its possible implication in CLS. Patient samples from 76 families were screened, and 1 patient was found to have a genomic deletion of approximately 2 kb. Amplification by RT-PCR of cDNA from the patient and direct sequencing showed a deletion of 187 bp between nucleotide positions 406 and 593 (300075.0001). The deletion produced a frameshift, generating a TAA termination codon 33 bp downstream of the deletion junction. The mutation cosegregated with CLS in 2 affected males and 1 female with discrete manifestations in this family. Trivier et al. (1996) then searched for point mutations and found both nonsense and missense mutations. Tissue-specific differences in gene expression suggested distinct physiologic roles for the various members of the RSK family (Moller et al., 1994; Zhao et al., 1995). RSK3 differs with respect to substrate specificity from other RSKs and may also have distinct upstream activators. Trivier et al. (1996) noted that in CLS, RSK1 and RSK3 are expressed at levels equivalent to those in normal individuals, indicating that they are not capable of overcoming the RSK2 deficiency. However, no abnormality of glycogen metabolism was found in CLS patients, although RSK2 was shown to be responsible for the activation of glycogen synthesis (Dent et al., 1990). </p><p>Jacquot et al. (1998) designed primers for PCR amplification of single exons from genomic DNA and subsequent SSCP analysis. They screened 37 patients with clinical features suggestive of CLS; 25 nucleotide changes predicted to be disease-causing mutations were identified, including 8 splice site alterations, 7 nonsense mutations, 5 frameshift mutations, and 5 missense mutations. Of the 25 mutations, 23 were novel. Coupled with previously reported mutations, these findings brought the total of different RSK2 mutations to 34. These were distributed throughout the RSK2 gene, with no clustering, and all but 2, which were found in 2 independent patients, were unique. A very high (68%) rate of de novo mutations was observed. Three mutations were found in female probands with no affected male relatives; these patients were ascertained through learning disability and mild but suggestive facial and digital dysmorphisms. No obvious correlation was observed between the position or type of the RSK2 mutations and the severity or particular clinical features of CLS. </p><p>Abidi et al. (1999) tested 5 unrelated individuals with CLS for mutations in 9 exons of the RSK2 gene using SSCP analysis. Two patients had the same missense mutation, 340C-T, predicted to cause an arg114-to-trp amino acid change (300075.0006). This mutation falls just outside the N-terminal ATP-binding site in a highly conserved region of the protein and may lead to structural changes since tryptophan has an aromatic side chain whereas arginine is a 5-carbon basic amino acid. The third patient had a 2186G-A nucleotide change, resulting in an arg729-to-gln missense mutation (300075.0009). The fourth patient had a 2-bp deletion (AG) of bases 451 and 452 (300075.0007). This created a frameshift that resulted in a stop codon 25 amino acids downstream, thereby producing a truncated protein. This deletion also falls within the highly conserved amino-catalytic domain of the protein. The fifth patient had a 2065C-T nucleotide change that resulted in a premature stop codon, thereby producing a truncated protein (300075.0008). Three of the patients in whom RSK2 mutations were identified by Abidi et al. (1999) had at least 1 brother who also carried the diagnosis of CLS. One of the 5 patients had a family history of mental retardation in male relatives, and his mother and aunt had been assessed as having intellectual impairment. All of the probands had large, soft hands with tapering fingers, severe to moderate mental retardation, short stature below the 5th centile, weight below the 5th centile, microcephaly, telecanthus or hypertelorism, and prominent eyes. Two were Caucasian; in these probands large mouth and prominent lower lips were observed. For the 3 African American probands this was difficult to evaluate because of the ethnic background. </p><p>Harum et al. (2001) noted that, based on evidence from experimental models, the transcription factor cAMP response element-binding protein (CREB; 123810) is thought to be involved in memory formation. RSK2 activates CREB through phosphorylation at serine-133. In 7 patients with CLS (5 boys and 2 girls), Harum et al. (2001) found a diminished activity of RSK2 to phosphorylate a CREB-like peptide in vitro in all cells lines. The authors noted a linear correlation between RSK2 activation of CREB and cognitive levels of the patients, consistent with the hypothesis that CREB is involved in human learning and memory. Other characteristics of the syndrome, including facial and bony abnormalities, may be due to impaired expression of various CREB-responsive genes. </p><p>By screening 250 patients with clinical features suggestive of Coffin-Lowry syndrome, Delaunoy et al. (2001) identified 71 distinct disease-associated RSK2 mutations in 86 unrelated families; 38% of the mutations were missense mutations, 20% were nonsense mutations, 18% were splicing errors, and 21% were short deletions or insertions. About 57% of the mutations resulted in premature translation termination, and most predicted loss of function of the mutant allele. The changes were distributed throughout the RSK2 gene and showed no obvious clustering or phenotypic association. However, some missense mutations were associated with milder phenotypes; in 1 family, 1 such mutation was associated solely with mild mental retardation. Nine mutations were found in female probands, with no affected male relatives, who had learning disability and mild facial and digital dysmorphism. </p><p>Zeniou et al. (2002) pointed out that in a series of 250 patients screened by SSCP analysis in whom the clinical diagnosis of CLS was made (Delaunoy et al., 2001), no mutations were detected in 165 (66%). To determine what proportion of these latter patients had an RSK2 mutation that had not been detected and what proportion have different disorders that are phenotypically similar to CLS, Zeniou et al. (2002) investigated, by Western blot analysis and in vitro kinase assay, cell lines from 26 patients in whom no mutation was previously identified by SSCP analysis. This approach allowed them to identify 7 novel RSK2 mutations: 2 changes in the coding sequence of RSK2, 1 intragenic deletion, and 4 unusual intronic nucleotide substitutions that did not affect the consensus GT or AG splice sites. No disease-causing nucleotide change was identified in the promoter region of the RSK2 gene. The results suggested that some patients have a disorder that is phenotypically very similar to CLS but is not caused by RSK2 defects. </p><p>Delaunoy et al. (2006) analyzed the RPS6KA3 gene in 120 patients with CLS and identified 45 mutations, of which 44 were novel, confirming the high rate of new mutations at the RSK2 locus. The authors noted that no mutation was found in over 60% of the patients referred to them for screening. Delaunoy et al. (2006) stated that of the 128 CLS mutations reported to date, 33% are missense mutations, 15% nonsense mutations, 20% splicing errors, and 29% short deletion or insertion events; and 4 large deletions have been reported. The mutations are distributed throughout the RPS6KA3 gene, and most mutations are private. </p><p>In a patient with a clinical phenotype highly suggestive of CLS in whom no mutation had been identified by sequencing PCR-amplified exons of RPS6KA3 from genomic DNA, Marques Pereira et al. (2007) analyzed the gene by direct sequencing of overlapping RT-PCR products and identified a direct tandem duplication spanning exactly exons 17 to 20 (300075.0019). The authors stated that this was the first reported large duplication in the RPS6KA3 gene. </p><p><strong><em>X-Linked Intellectual Developmental Disorder 19</em></strong></p><p>
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In affected members of a family with nonsyndromic X-linked intellectual developmental disorder-19 (XLID19; 300844), Merienne et al. (1999) identified a missense mutation (300075.0010) in the RPS6KA3 gene. Patients exhibited none of the facial, digital, or skeletal features or the abnormal posture or gait typical of Coffin-Lowry syndrome. </p><p>Field et al. (2006) identified 3 different mutations in the RPS6KA3 gene (see, e.g., 300075.0020-300075.0021) in affected members of 3 unrelated families with nonsyndromic X-linked mental retardation. The patients had some variable features reminiscent of Coffin-Lowry syndrome, such as coarse facial features, kyphoscoliosis, short stature, and some redundancy of palmar skin with horizontal creases, but these additional features were considered to be too mild or atypical for a diagnosis of CLS. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The level of residual RPS6KA3 activity seems to be related to the severity of the phenotype. Merienne et al. (1999) demonstrated 10 to 20% residual enzymatic activity in patients with nonsyndromic MRX19, which was postulated to result in the relatively mild phenotype without skeletal anomalies (300075.0010). The patients reported by Field et al. (2006) with nonsyndromic X-linked mental retardation also had a milder phenotype, which the authors thought likely resulted from residual protein activity. Field et al. (2006) noted that the mutations in their report and the mutation (300075.0011) reported by Manouvrier-Hanu et al. (1999) in a family with mild Coffin-Lowry syndrome were small in-frame deletions or missense mutations affecting the serine/threonine kinase domain. Field et al. (2006) hypothesized that the presence of a small amount of residual enzymatic activity may be sufficient to maintain normal osteoblast differentiation and ameliorate the skeletal phenotype associated with CLS. The level of residual enzymatic activity has also been linked to cognitive performance, with higher levels being associated with a higher level of intellectual function (Harum et al., 2001). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using Rsk2 -/- mice, Yang et al. (2004) showed that RSK2 is required for osteoblast differentiation and function. They identified the transcription factor ATF4 (604064) as a critical substrate of RSK2 that is required for the timely onset of osteoblast differentiation, for terminal differentiation of osteoblasts, and for osteoblast-specific gene expression. Additionally, RSK2 and ATF4 were found to posttranscriptionally regulate the synthesis of type I collagen (see 120150), the main constituent of the bone matrix. Accordingly, Atf4 deficiency in mice resulted in delayed bone formation during embryonic development and low bone mass throughout postnatal life. Yang et al. (2004) concluded that ATF4 is a critical regulator of osteoblast differentiation and function and that lack of ATF4 phosphorylation by RSK2 may contribute to the skeletal phenotype of Coffin-Lowry syndrome. </p><p>David et al. (2005) demonstrated that Rsk2-null mice develop progressive osteopenia due to impaired osteoblast function and normal osteoclast differentiation. They also observed that c-fos (164810)-dependent osteosarcoma formation was impaired in the absence of Rsk2; the lack of c-fos phosphorylation led to reduced c-fos protein levels, which were thought to be responsible for the observed decreased proliferation and increased apoptosis of transformed osteoblasts. David et al. (2005) concluded that Rsk2-dependent stabilization of c-fos is essential for osteosarcoma formation in mice. </p><p>Poirier et al. (2007) found that Rsk2-null mice showed a mild impairment in spatial working memory, delayed acquisition of a spatial reference memory task, and long-term spatial memory deficits. In contrast, associative and recognition memory, as well as the habituation of exploratory activity were normal. The studies also revealed mild signs of disinhibition in exploratory activity, as well as a difficulty to adapt to new test environments, which likely contributed to the learning impairments displayed by Rsk2-null mice. There were no obvious brain abnormalities at the anatomic and histologic level. The behavioral changes observed supported a role for Rsk2 in cognitive functions. </p><p>Marques Pereira et al. (2008) found that Rsk2-null mice had increased cortical dopamine levels and overexpression of the DRD2 receptor (126450) and dopamine transporter (SLC6A3; 126455). Evidence also suggested that the dopaminergic dysregulation may have been caused, at least in part, by increased tyrosine hydroxylase (TH; 191290) hyperactivity. The authors suggested that these neurotransmitters changes may explain some of the cognitive alterations in Rsk2-null mice. </p><p>Using microarray analysis, Mehmood et al. (2011) identified 100 genes that were differentially expressed in Rsk2 -/- mice compared with wildtype, and they confirmed differential expression of 24 of these genes using quantitative RT-PCR. Genes that were affected by Rsk2 deletion had roles in cell differentiation, proliferation, apoptosis, cell cycle, free radical scavenging, and nervous system development and function. Mehmood et al. (2011) characterized the consequences of 2-fold upregulation of the Gria2 gene (138247), which encodes a subunit of the AMPA glutamate receptor. Immunohistochemical analysis revealed significantly increased surface expression of Gria2 protein in Rsk2 -/- neurons. However, patch-clamp analysis showed significantly decreased basal AMPA receptor-mediated transmission in Rsk2 -/- hippocampal neurons. These changes in Gria2 protein expression and function appeared to be due to altered Gria2 mRNA editing and splicing in Rsk2 -/- mice. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>22 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 COFFIN-LOWRY SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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RPS6KA3, 187-BP DEL, NT406
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<br />
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ClinVar: RCV000012416
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Of 76 families segregating for CLS (303600), Trivier et al. (1996) identified one in which affected members had an approximately 2-kb deletion of the RPS6KA3 gene. By RT-PCR followed by direct sequencing, they demonstrated a deletion of 187 bp between nucleotides 406 and 593. The deletion produced a frameshift, generating a TAA termination codon 33 bp downstream of the deletion junction. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 COFFIN-LOWRY SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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RPS6KA3, GLY75VAL
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<br />
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SNP: rs122454124,
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ClinVar: RCV000012417
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with CLS (303600), Trivier et al. (1996) demonstrated a G-to-T transition at nucleotide 224 in the RSK2 gene, resulting in a gly75-to-val substitution. Gly75 is a conserved residue located within the putative ATP-binding site. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 COFFIN-LOWRY SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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RPS6KA3, SER227ALA
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<br />
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SNP: rs122454125,
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ClinVar: RCV000012418
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with CLS (303600), Trivier et al. (1996) demonstrated a T-to-G transition at nucleotide 679 in the RSK2 gene, resulting in a ser227-to-ala substitution. Ser227 is a conserved residue, and is believed to be a phosphorylation site of the kinase domain of the N terminus, which is essential for catalytic function. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 COFFIN-LOWRY SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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RPS6KA3, VAL82PHE
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<br />
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SNP: rs122454126,
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ClinVar: RCV000012419
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a familial case of CLS (303600), Jacquot et al. (1998) found a 244G-T transversion in exon 4, resulting in a val82-to-phe amino acid substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 COFFIN-LOWRY SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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RPS6KA3, IVS4AS, G-C, -1
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|
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<br />
|
|
|
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SNP: rs587776755,
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|
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|
|
ClinVar: RCV000012420
|
|
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|
|
|
</span>
|
|
</div>
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|
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|
|
|
<div>
|
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<span class="mim-text-font">
|
|
<p>Jacquot et al. (1998) identified a Coffin-Lowry syndrome (303600) pedigree in which the disorder was associated with a novel splice site mutation in the RSK2 gene, leading to in-frame skipping of exon 5: a G-to-C transition in the splice acceptor site (position -1) immediately upstream of exon 5. Western blot analysis, using an antibody directed against the C terminus of the RSK2 protein, failed to reveal RSK2 protein in this patient, suggesting strongly that the internally deleted protein was unstable. The mutation was present in the DNA of 1 affected son and 1 manifesting daughter but was absent in 2 asymptomatic daughters, who carried the at-risk haplotype, and in the mother's somatic cell (lymphocyte) DNA. The results were considered consistent with the mutation having arisen as a postzygotic event in the mother, who therefore was a germinal mosaic. The mother was clinically normal but, in addition to strong wildtype bands shown on SSCP analysis, there were very faint bands corresponding to a small proportion (less than 1%) of mutated DNA. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
|
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 COFFIN-LOWRY SYNDROME</strong>
|
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</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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RPS6KA3, ARG114TRP
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<br />
|
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|
|
SNP: rs122454127,
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|
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ClinVar: RCV000012421
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|
|
|
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</span>
|
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</div>
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|
|
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<div>
|
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<span class="mim-text-font">
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<p>In 2 unrelated African American patients with CLS (303600), Abidi et al. (1999) observed an arg114-to-trp missense mutation resulting from a 340C-T nucleotide change in the RSK2 gene. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
|
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</div>
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</div>
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|
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, 2-BP DEL, 451AG
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<br />
|
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|
|
SNP: rs1603426295,
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|
|
|
|
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ClinVar: RCV000012422, RCV004760327
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with CLS (303600), Abidi et al. (1999) found that the RSK2 gene contained a 2-bp deletion of bases 451A and 452G, causing a frameshift that resulted in a stop codon 25 amino acids downstream and thereby producing a truncated protein. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
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|
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</div>
|
|
|
|
|
|
<div>
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, GLN689TER
|
|
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|
|
<br />
|
|
|
|
SNP: rs122454128,
|
|
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|
|
|
|
|
ClinVar: RCV000012423
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In an African American patient with CLS (303600), Abidi et al. (1999) found a 2065C-T transition that gave rise to a premature stop codon (gln689 to ter), and a truncated protein lacking the last 51 amino acids of the RSK2 gene. </p>
|
|
</span>
|
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</div>
|
|
|
|
|
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
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</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, ARG729GLN
|
|
|
|
|
|
<br />
|
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|
|
SNP: rs28935171,
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|
|
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ClinVar: RCV000012424, RCV000413967, RCV001257622, RCV001266366
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with CLS (303600), Abidi et al. (1999) found a 2186G-A nucleotide change in the RSK2 gene, resulting in an arg729-to-gln missense mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 19</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, ARG383TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs122454129,
|
|
|
|
|
|
|
|
ClinVar: RCV000012425
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with nonsyndromic X-linked intellectual developmental disorder-19 (XLID19; 300844), Merienne et al. (1999) identified a 1147C-T transition in exon 14 of the RPS6KA3 gene, resulting in an arg383-to-trp (R383W) substitution. This mutation occurred in a CpG dinucleotide motif. Reexamination of 2 of the affected individuals, then 38 and 29 years old, showed that they exhibited none of the facial, digital, or skeletal features or the abnormal posture or gait typical of Coffin-Lowry syndrome (303600). Furthermore, both presented with very mild mental retardation, compatible with social autonomy. It had previously been found that most CLS-producing mutations inactivate RPS6KA3. The mutation in the family reported by Merienne et al. (1999) was notable in that the 5- to 6-fold decrease in kinase activity resulted in a mild phenotype. This demonstrated that 15 to 20% of RPS6KA3 activity is sufficient for normal signaling of the MAPK-RPS6KA3 pathway involved in skeletal development. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 COFFIN-LOWRY SYNDROME, MILD</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, ILE189LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs122454130,
|
|
|
|
|
|
|
|
ClinVar: RCV000012426
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Manouvrier-Hanu et al. (1999) reported 2 male sibs with a mild form of CLS (303600) who had a T-to-A transversion in exon 7 of the RPS6KA3 gene leading to the substitution of a lysine residue in place of an isoleucine residue at position 189 (I189K). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, IVS6, A-G, +3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1603426293,
|
|
|
|
|
|
|
|
ClinVar: RCV000012427
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Coffin-Lowry syndrome (303600), Zeniou et al. (2002) identified an IVS6+3A-G intronic mutation of the RPS6KA3 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, IVS5, A-G, -11
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1555943503,
|
|
|
|
|
|
|
|
ClinVar: RCV000623700, RCV001798931, RCV004702205
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Coffin-Lowry syndrome (303600), Zeniou et al. (2002) identified an IVS5-11A-G intronic mutation of the RPS6KA3 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, 1-BP DEL, 2144C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1603417213,
|
|
|
|
|
|
|
|
ClinVar: RCV000012429
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male infant native to the Cook Islands with Coffin-Lowry syndrome (303600), McGaughran and Delaunoy (2002) identified a 1-bp deletion (2144delC) in the RPS6KA3 gene, resulting in a stop codon 21 amino acids before the normal termination codon. The proband was the sixth child of nonconsanguineous parents; the fifth child, also male, died at age 7 months, presumably of the same condition. The proband's inner canthal distance was greater than the 97th centile. He had large anterior and posterior fontanels, mild synophrys, and a long philtrum. His fingers were flattened and tapering. His mother's fingers had a similar but more marked appearance. Her facial appearance was consistent with the diagnosis of heterozygous carrier of CLS, but she did not undergo molecular testing. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, IVS12, A-G, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2148664125,
|
|
|
|
|
|
|
|
ClinVar: RCV000012430
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Fryssira et al. (2002) described a female patient with full-blown CLS (303600), manifested by facial dysmorphism, tapering fingers, and skeletal deformities (pectus excavatum and kyphoscoliosis), who was found to have an A-to-G transition in the RSK2 gene, creating a suppression of the splicing site between intron 12 and exon 13. Her overall IQ was 53. At the age of 9 years, there was onset of a cataplexy-like phenomenon characterized by a sudden and reversible loss of muscle tone without loss of consciousness. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, IVS3, L1 INS, -8
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000012431
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Coffin-Lowry syndrome (303600), Martinez-Garay et al. (2003) identified a de novo insertion of a 5-prime truncated LINE-1 element at position -8 of intron 3 of the RPS6KA3, which led to skipping of exon 4, a shift of the reading frame, and a premature stop codon. The 2,800-bp L1 fragment showed a rearrangement with a small deletion and a partial inversion of ORF2, flanked by short direct repeats that duplicated the acceptor splice site. A cDNA analysis showed that both sites were apparently nonfunctional. The 30-year-old patient had mental retardation, hypotonia, sensorineural hearing deficit, downslanting palpebral fissures, broad nose, anteverted nares, large mouth, thick everted lips, large and everted ears, pectus carinatum, tapering fingers with drumstick terminal phalanges, forearm fullness, and flat feet. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, PHE268SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs122454131,
|
|
|
|
|
|
|
|
ClinVar: RCV000012432
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In monozygotic twins with Coffin-Lowry syndrome (303600) and in their mother, who was mildly affected, Martinez-Garay et al. (2003) identified an 803T-C transition in exon 10 of the RPS6KA3 gene, which resulted in a phe268-to-ser (F268S) substitution. The mother showed tapering fingers, obesity, large mouth, and large and dysplastic ears. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, 3-BP DEL, 1428TAT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1603420690,
|
|
|
|
|
|
|
|
ClinVar: RCV000012433
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old boy with physical and developmental findings consistent with Coffin-Lowry syndrome (303600), Facher et al. (2004) identified a 3-bp deletion (TAT) at position 1428 of the RPS6KA3 gene, resulting in the loss of an isoleucine. The patient was unusual in that he had restrictive cardiomyopathy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 COFFIN-LOWRY SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RPS6KA3, DUP EXONS 17-20, NT1959
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<br />
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ClinVar: RCV000012434
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an 1.5-year-old boy with Coffin-Lowry syndrome (303600), Marques Pereira et al. (2007) identified an in-frame tandem duplication of exons 17 to 20, resulting from insertion of 516 nucleotides at nucleotide 1959, that arose from a homologous unequal recombination between Alu sequences. In vitro kinase assay showed that mutant RSK2 was inactive. The patient's mother, who had childhood scoliosis and difficulties in school, was found to carry the mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0020 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 19</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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RPS6KA3, 3-BP DEL, 454GGA
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<br />
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SNP: rs398122813,
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ClinVar: RCV000022822
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with nonsyndromic X-linked intellectual developmental disorder-19 (XLID19; 300844), Field et al. (2006) identified an in-frame 3-bp deletion (454delGGA) in the RPS6KA3 gene, resulting in the deletion of gly152. This residue is highly conserved and located in the serine/threonine protein kinase domain. The patients had coarse facial features, kyphoscoliosis, and some redundancy of palmar skin with horizontal creases, but no digital tapering or short stature. These additional features were considered to be too mild for a diagnosis of Coffin-Lowry syndrome (303600). Field et al. (2006) hypothesized that the mutant protein had a small amount of residual activity, which likely explained the relatively mild phenotype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0021 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 19</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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RPS6KA3, THR115SER
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<br />
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SNP: rs387906703,
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ClinVar: RCV000022823
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 brothers with nonsyndromic X-linked intellectual developmental disorder-19 (XLID19; 300844), Field et al. (2006) identified a 343A-T transversion in the RPS6KA3 gene, resulting in a thr115-to-ser (T115S) substitution in a highly conserved region in the serine/threonine protein kinase domain. The patients had short stature, hypertelorism, and a slightly full lower lip, but these features were considered to be too subtle for a diagnosis of Coffin-Lowry syndrome (303600). Field et al. (2006) hypothesized that the mutant protein had a small amount of residual activity, which likely explained the relatively mild phenotype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0022 COFFIN-LOWRY SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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RPS6KA3, 7.2-KB DEL
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<br />
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ClinVar: RCV000170489
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In cells derived from an affected member of the original family with Coffin-Lowry syndrome (CLS; 303600) reported by Lowry et al. (1971), Nishimoto et al. (2014) identified an in-frame deletion of exons 15 and 16 (r.1228_1443del216) in the RPS6KA3 gene, resulting in the deletion of 72 amino acids from 410 to 418 in the C-terminal kinase domain, predicting the loss of function of this domain. Microarray analysis indicated that the maximum size of the deletion was about 7.2 kb. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Abidi, F., Jacquot, S., Lassiter, C., Trivier, E., Hanauer, A., Schwartz, C. E.
|
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<strong>Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).</strong>
|
|
Europ. J. Hum. Genet. 7: 20-26, 1999.
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[PubMed: 10094187]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5200231]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Bjorbaek, C., Vik, T. A., Echwald, S. M., Yang, P.-Y., Vestergaard, H., Wang, J. P., Webb, G. C., Richmond, K., Hansen, T., Erikson, R. L., Gabor Miklos, G. L., Cohen, P. T. W., Pederson, O.
|
|
<strong>Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients.</strong>
|
|
Diabetes 44: 90-97, 1995.
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[PubMed: 7813820]
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[Full Text: https://doi.org/10.2337/diab.44.1.90]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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David, J.-P., Mehic, D., Bakiri, L., Schilling, A. F., Mandic, V., Priemel, M., Idarraga, M. H., Reschke, M. O., Hoffmann, O., Amling, M., Wagner, E. F.
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<strong>Essential role of RSK2 in c-Fos-dependent osteosarcoma development.</strong>
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|
J. Clin. Invest. 115: 664-672, 2005.
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[PubMed: 15719069]
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[Full Text: https://doi.org/10.1172/JCI22877]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Delaunoy, J. P., Dubos, A., Marques Pereira, P., Hanauer, A.
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<strong>Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome.</strong>
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Clin. Genet. 70: 161-166, 2006.
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[PubMed: 16879200]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2006.00660.x]
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</p>
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<li>
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<p class="mim-text-font">
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Delaunoy, J.-P., Abidi, F., Zeniou, M., Jacquot, S., Merienne, K., Pannetier, S., Schmitt, M., Schwartz, C. E., Hanauer, A.
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<strong>Mutations in the X-linked RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome.</strong>
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Hum. Mutat. 17: 103-116, 2001.
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[PubMed: 11180593]
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[Full Text: https://doi.org/10.1002/1098-1004(200102)17:2<103::AID-HUMU2>3.0.CO;2-N]
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<p class="mim-text-font">
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Dent, P., Lavoinne, A., Nekielny, S., Caudwell, F. B., Watt, P., Cohen, P.
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<strong>The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle.</strong>
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Nature 348: 302-308, 1990.
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[PubMed: 2123524]
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[Full Text: https://doi.org/10.1038/348302a0]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Facher, J. J., Regier, E. J., Jacobs, G. H., Siwik, E., Delaunoy, J.-P., Robin, N. H.
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<strong>Cardiomyopathy in Coffin-Lowry syndrome.</strong>
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Am. J. Med. Genet. 128A: 176-178, 2004.
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[PubMed: 15214012]
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[Full Text: https://doi.org/10.1002/ajmg.a.30056]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Field, M., Tarpey, P., Boyle, J., Edkins, S., Goodship, J., Luo, Y., Moon, J., Teague, J., Stratton, M. R., Futreal, P. A., Wooster, R., Raymond, F. L., Turner, G.
|
|
<strong>Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation.</strong>
|
|
Clin. Genet. 70: 509-515, 2006.
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[PubMed: 17100996]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2006.00723.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Fryssira, H., Kountoupi, S., Delaunoy, J. P., Thomaidis, L.
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<strong>A female with Coffin-Lowry syndrome and 'cataplexy'.</strong>
|
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Genet. Counsel. 13: 405-409, 2002.
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[PubMed: 12558110]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Harum, K. H., Alemi, L., Johnston, M. V.
|
|
<strong>Cognitive impairment in Coffin-Lowry syndrome correlates with reduced RSK2 activation.</strong>
|
|
Neurology 56: 207-214, 2001.
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[PubMed: 11160957]
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[Full Text: https://doi.org/10.1212/wnl.56.2.207]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Jacquot, S., Merienne, K., De Cesare, D., Pannetier, S., Mandel, J.-L., Sassone-Corsi, P., Hanauer, A.
|
|
<strong>Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations.</strong>
|
|
Am. J. Hum. Genet. 63: 1631-1640, 1998.
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[PubMed: 9837815]
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[Full Text: https://doi.org/10.1086/302153]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Jacquot, S., Merienne, K., Pannetier, S., Blumenfeld, S., Schinzel, A., Hanauer, A.
|
|
<strong>Germline mosaicism in Coffin-Lowry syndrome.</strong>
|
|
Europ. J. Hum. Genet. 6: 578-582, 1998.
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[PubMed: 9887375]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5200230]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Lowry, R. B., Miller, J. R., Fraser, F. C.
|
|
<strong>A new dominant gene mental retardation syndrome: associated with small stature, tapering fingers, characteristic facies, and possible hydrocephalus.</strong>
|
|
Am. J. Dis. Child. 121: 496-500, 1971.
|
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|
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[PubMed: 5581017]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Manouvrier-Hanu, S., Amiel, J., Jacquot, S., Merienne, K., Moerman, A., Coeslier, A., Labarriere, F., Vallee, L., Croquette, M. F., Hanauer, A.
|
|
<strong>Unreported RSK2 missense mutation in two male sibs with an unusually mild form of Coffin-Lowry syndrome.</strong>
|
|
J. Med. Genet. 36: 775-778, 1999.
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[PubMed: 10528858]
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[Full Text: https://doi.org/10.1136/jmg.36.10.775]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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|
Marques Pereira, P., Gruss, M., Braun, K., Foos, N., Pannetier, S., Hanauer, A.
|
|
<strong>Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin-Lowry syndrome.</strong>
|
|
J. Neurochem. 107: 1325-1334, 2008.
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[PubMed: 18823370]
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[Full Text: https://doi.org/10.1111/j.1471-4159.2008.05703.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Marques Pereira, P., Heron, D., Hanauer, A.
|
|
<strong>The first large duplication of the RSK2 gene identified in a Coffin-Lowry syndrome patient.</strong>
|
|
Hum. Genet. 122: 541-543, 2007.
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|
|
[PubMed: 17717706]
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[Full Text: https://doi.org/10.1007/s00439-007-0424-1]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Marques Pereira, P., Schneider, A., Pannetier, S., Heron, D., Hanauer, A.
|
|
<strong>Coffin-Lowry syndrome.</strong>
|
|
Europ. J. Hum. Genet. 18: 627-633, 2010.
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[PubMed: 19888300]
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[Full Text: https://doi.org/10.1038/ejhg.2009.189]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Martinez-Garay, I., Ballesta, M. J., Oltra, S., Orellana, C., Palomeque, A., Molto, M. D., Prieto, F., Martinez, F.
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<strong>Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing Coffin-Lowry syndrome.</strong>
|
|
Clin. Genet. 64: 491-496, 2003.
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|
[PubMed: 14986828]
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[Full Text: https://doi.org/10.1046/j.1399-0004.2003.00166.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
McGaughran, J., Delaunoy, J.-P.
|
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<strong>Coffin-Lowry syndrome in a patient from the Cook Islands confirmed by the presence of a unique mutation. (Letter)</strong>
|
|
Am. J. Med. Genet. 113: 309-311, 2002.
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[PubMed: 12439904]
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[Full Text: https://doi.org/10.1002/ajmg.10786]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Mehmood, T., Schneider, A., Sibille, J., Pereira, P. M., Pannetier, S., Ammar, M. R., Dembele, D., Thibault-Carpentier, C., Rouach, N., Hanauer, A.
|
|
<strong>Transcriptome profile reveals AMPA receptor dysfunction in the hippocampus of the Rsk2-knockout mice, an animal model of Coffin-Lowry syndrome.</strong>
|
|
Hum. Genet. 129: 255-269, 2011. Note: Erratum: Hum. Genet. 129: 271 only, 2011.
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[PubMed: 21116650]
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[Full Text: https://doi.org/10.1007/s00439-010-0918-0]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Merienne, K., Jacquot, S., Pannetier, S., Zeniou, M., Bankier, A., Gecz, J., Mandel, J.-L., Mulley, J., Sassone-Corsi, P., Hanauer, A.
|
|
<strong>A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation. (Letter)</strong>
|
|
Nature Genet. 22: 13-14, 1999.
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|
[PubMed: 10319851]
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[Full Text: https://doi.org/10.1038/8719]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Moller, D. E., Xia, C. H., Tang, W., Zhu, A. X., Jakubowski, M.
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|
<strong>Human rsk isoforms: cloning and characterization of tissue-specific expression.</strong>
|
|
Am. J. Physiol. 266: C351-C359, 1994.
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|
|
[PubMed: 8141249]
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[Full Text: https://doi.org/10.1152/ajpcell.1994.266.2.C351]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Nishimoto, H. K., Ha, K., Jones, J. R., Dwivedi, A., Cho, H.-M., Layman, L. C., Kim, H.-G.
|
|
<strong>The historical Coffin-Lowry syndrome family revisited: identification of two novel mutations of RPS6KA3 in three male patients.</strong>
|
|
Am. J. Med. Genet. 164A: 2172-2179, 2014.
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[PubMed: 25044551]
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[Full Text: https://doi.org/10.1002/ajmg.a.36488]
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</p>
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</li>
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Poirier, R., Jacquot, S., Vaillend, C., Soutthiphong, A. A., Libbey, M., Davis, S., Laroche, S., Hanauer, A., Welzl, H., Lipp, H.-P., Wolfer, D. P.
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Vigneron, S., Brioudes, E., Burgess, A., Labbe, J.-C., Lorca, T., Castro, A.
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Zhao, Y., Bjorbaek, C., Weremowicz, S., Morton, C. C., Moller, D. E.
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