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Entry
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- *609891 - RIPPLY TRANSCRIPTIONAL REPRESSOR 2; RIPPLY2
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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">*609891</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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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="#cloning">Cloning and Expression</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="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/609891">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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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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</ul>
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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 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=ENSG00000203877;t=ENST00000369689" 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=134701" 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=609891" 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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<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=ENSG00000203877;t=ENST00000369689" 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_001009994,NM_001400899,NM_001400900,NR_103525,NR_174622" 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_001009994" 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=609891" 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=16658&isoform_id=16658_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/RIPPLY2" 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/58000465,74745808,119569036,120659884,124376230,2185419464,2185421460" 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/Q5TAB7" 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=134701" 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=ENSG00000203877;t=ENST00000369689" 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=RIPPLY2" 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=RIPPLY2" 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+134701" 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/RIPPLY2" 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:134701" 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/134701" 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=chr6&hgg_gene=ENST00000369689.6&hgg_start=83853229&hgg_end=83857515&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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=609891[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>
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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=609891[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://gnomad.broadinstitute.org/gene/ENSG00000203877" 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.gwascentral.org/search?q=RIPPLY2" 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=RIPPLY2" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=RIPPLY2&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/PA162401349" 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:21390" 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://www.mousephenotype.org/data/genes/MGI:2685968" 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/RIPPLY2#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:2685968" 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/134701/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=134701" 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://zfin.org/ZDB-GENE-060113-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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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://reactome.org/content/query?q=RIPPLY2&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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</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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609891
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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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RIPPLY TRANSCRIPTIONAL REPRESSOR 2; RIPPLY2
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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">
|
|
CHROMOSOME 6 OPEN READING FRAME 59; C6ORF59
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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=RIPPLY2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">RIPPLY2</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/6/678?start=-3&limit=10&highlight=678">6q14.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:83853229-83857515&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'})">6:83,853,229-83,857,515</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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</th>
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<th>
|
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
|
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<th>
|
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
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<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/6/678?start=-3&limit=10&highlight=678">
|
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6q14.2
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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?Spondylocostal dysostosis 6
|
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<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
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</span>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/616566"> 616566 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</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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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/609891" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/609891" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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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="text" class="mim-anchor"></a>
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<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
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</h4>
|
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<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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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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<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
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<span class="mim-text-font">
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<p>By searching for sequences similar to that of zebrafish Ripply1 (<a href="/entry/300575">300575</a>), <a href="#4" class="mim-tip-reference" title="Kawamura, A., Koshida, S., Hijikata, H., Ohbayashi, A., Kondoh, H., Takada, S. <strong>Groucho-associated transcriptional repressor Ripply1 is required for proper transition from the presomitic mesoderm to somites.</strong> Dev. Cell 9: 735-744, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16326386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16326386</a>] [<a href="https://doi.org/10.1016/j.devcel.2005.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16326386">Kawamura et al. (2005)</a> identified human RIPPLY2. The deduced 128-amino acid protein contains a WRPW tetrapeptide near its N terminus and a conserved domain of about 50 amino acids found in other Ripply proteins. In zebrafish embryos, Ripply2 was expressed in the paraxial mesoderm and was subsequently confined to the presomitic mesoderm. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16326386" 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="Chan, T., Kondow, A., Hosoya, A., Hitachi, K., Yukita, A., Okabayashi, K., Nakamura, H., Ozawa, H., Kiyonari, H., Michiue, T., Ito, Y., Asashima, M. <strong>Ripply2 is essential for precise somite formation during mouse early development.</strong> FEBS Lett. 581: 2691-2696, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17531978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17531978</a>] [<a href="https://doi.org/10.1016/j.febslet.2007.05.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17531978">Chan et al. (2007)</a> found that Ripply2 was expressed in presomitic mesoderm in day-9.0 and -11.5 mouse embryos, concomitant with somite formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17531978" 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="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 9/22/2015."None>Gross (2015)</a> mapped the RIPPLY2 gene to chromosome 6q14.2 based on an alignment of the RIPPLY2 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC130460" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC130460</a>) with the genomic sequence (GRCh38).</p>
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In 2 brothers with segmentation defects of the vertebrae (SCDO6; <a href="/entry/616566">616566</a>), <a href="#5" class="mim-tip-reference" title="McInerney-Leo, A. M., Sparrow, D. B., Harris, J. E., Gardiner, B. B., Marshall, M. S., O'Reilly, V. C., Shi, H., Brown, M. A., Leo, P. J., Zankl, A., Dunwoodie, S. L., Duncan, E. L. <strong>Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects.</strong> Hum. Molec. Genet. 24: 1234-1242, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25343988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25343988</a>] [<a href="https://doi.org/10.1093/hmg/ddu534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25343988">McInerney-Leo et al. (2015)</a> identified compound heterozygosity for a nonsense mutation (R80X; <a href="#0001">609891.0001</a>) and a splice site mutation (c.240-4T-G; <a href="#0002">609891.0002</a>) in the RIPPLY2 gene that segregated with disease in the family. Analysis of in-house sequencing data from 991 individuals with unrelated disorders did not detect any with compound heterozygous variants in RIPPLY2. <a href="#5" class="mim-tip-reference" title="McInerney-Leo, A. M., Sparrow, D. B., Harris, J. E., Gardiner, B. B., Marshall, M. S., O'Reilly, V. C., Shi, H., Brown, M. A., Leo, P. J., Zankl, A., Dunwoodie, S. L., Duncan, E. L. <strong>Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects.</strong> Hum. Molec. Genet. 24: 1234-1242, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25343988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25343988</a>] [<a href="https://doi.org/10.1093/hmg/ddu534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25343988">McInerney-Leo et al. (2015)</a> noted that a rare variant (minor allele frequency less than 0.01) was detected in 1 of 1,982 alleles, thus the probability of 2 rare variants occurring by chance would be 2.54 x 10(-7), and the probability of both segregating appropriately within the family would be even lower. In addition, functional analysis demonstrated significantly reduced transcriptional repression activity with the R80X mutant compared to wildtype RIPPLY2. The authors stated that they were unable to demonstrate a functional consequence of the c.240-4T-G mutation because of its location in the terminal exon splice site consensus sequence and the likely restriction of RIPPLY2 expression to embryogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25343988" 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>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between mutation in the RIPPLY2 gene and Klippel-Feil syndrome (see <a href="/entry/214300">214300</a>), see <a href="#0003">609891.0003</a>.</p>
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<p><a href="#1" class="mim-tip-reference" title="Chan, T., Kondow, A., Hosoya, A., Hitachi, K., Yukita, A., Okabayashi, K., Nakamura, H., Ozawa, H., Kiyonari, H., Michiue, T., Ito, Y., Asashima, M. <strong>Ripply2 is essential for precise somite formation during mouse early development.</strong> FEBS Lett. 581: 2691-2696, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17531978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17531978</a>] [<a href="https://doi.org/10.1016/j.febslet.2007.05.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17531978">Chan et al. (2007)</a> obtained Ripply2 -/- mice at the expected mendelian ratio, but all died soon after birth without breathing. At embryonic day 18, Ripply2 -/- mice had shortened tails, truncated body axis, and defects in vertebral bodies, intervertebral discs, and neural arches. Pedicles of neural arches were fused or missing. Ribs in Ripply2 -/- mice were fused and bifurcated and showed loss of symmetry about the left-right axis, and they were reduced in number. Skull and limbs appeared normal. Skeletal malformations observed in Ripply2 -/- mice appeared to be due to defective somite segmentation. Expression of Notch2 (<a href="/entry/600275">600275</a>) and Uncx4.1 was disrupted in Ripply2 -/- mice. <a href="#1" class="mim-tip-reference" title="Chan, T., Kondow, A., Hosoya, A., Hitachi, K., Yukita, A., Okabayashi, K., Nakamura, H., Ozawa, H., Kiyonari, H., Michiue, T., Ito, Y., Asashima, M. <strong>Ripply2 is essential for precise somite formation during mouse early development.</strong> FEBS Lett. 581: 2691-2696, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17531978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17531978</a>] [<a href="https://doi.org/10.1016/j.febslet.2007.05.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17531978">Chan et al. (2007)</a> concluded that RIPPLY2 is involved in somite segmentation and establishment of rostrocaudal polarity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17531978" 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="#5" class="mim-tip-reference" title="McInerney-Leo, A. M., Sparrow, D. B., Harris, J. E., Gardiner, B. B., Marshall, M. S., O'Reilly, V. C., Shi, H., Brown, M. A., Leo, P. J., Zankl, A., Dunwoodie, S. L., Duncan, E. L. <strong>Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects.</strong> Hum. Molec. Genet. 24: 1234-1242, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25343988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25343988</a>] [<a href="https://doi.org/10.1093/hmg/ddu534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25343988">McInerney-Leo et al. (2015)</a> analyzed the skeletal development of Ripply2 +/- mice at embryonic day 14.5 and observed that 1 of 33 embryos exhibited a slight vertebral defect (unilateral interruption of the lamina of S1), whereas all 40 wildtype embryos were normal. The authors concluded that loss of 1 Ripply1 allele did not cause vertebral defects with significant penetrance. Analysis of similar embryos exposed to short-term mild hypoxia during pregnancy revealed that 4 of 30 heterozygous embryos had mild defects, each involving a single vertebra, compared to 1 of 35 wildtype embryos; thus, hypoxia did not significantly increase the penetrance or severity of vertebral defects in Ripply2 +/- embryos. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25343988" 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=609891[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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs201419367 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs201419367;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs201419367?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs201419367" 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=rs201419367" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 brothers (family SKDP-10) with segmentation defects of the vertebrae (SCDO6; <a href="/entry/616566">616566</a>), <a href="#5" class="mim-tip-reference" title="McInerney-Leo, A. M., Sparrow, D. B., Harris, J. E., Gardiner, B. B., Marshall, M. S., O'Reilly, V. C., Shi, H., Brown, M. A., Leo, P. J., Zankl, A., Dunwoodie, S. L., Duncan, E. L. <strong>Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects.</strong> Hum. Molec. Genet. 24: 1234-1242, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25343988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25343988</a>] [<a href="https://doi.org/10.1093/hmg/ddu534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25343988">McInerney-Leo et al. (2015)</a> identified compound heterozygosity for 2 mutations in the RIPPLY2 gene: a c.238A-T transversion (c.238A-T, NM_001009994) in exon 3 of the RIPPLY2 gene, resulting in an arg80-to-ter (R80X) substitution, and a c.240-4T-G transversion in intron 3 (<a href="#0002">609891.0002</a>) at the 5-prime predicted splice acceptor site for exon 4. Their unaffected parents were each heterozygous for 1 of the mutations, as was the unaffected maternal grandmother, whereas their unaffected sister did not carry either of the mutations. <a href="#5" class="mim-tip-reference" title="McInerney-Leo, A. M., Sparrow, D. B., Harris, J. E., Gardiner, B. B., Marshall, M. S., O'Reilly, V. C., Shi, H., Brown, M. A., Leo, P. J., Zankl, A., Dunwoodie, S. L., Duncan, E. L. <strong>Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects.</strong> Hum. Molec. Genet. 24: 1234-1242, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25343988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25343988</a>] [<a href="https://doi.org/10.1093/hmg/ddu534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25343988">McInerney-Leo et al. (2015)</a> noted that the R80X mutation causes loss of 49 C-terminal amino acids, including the highly conserved Ripply homology domain required for direct protein-protein interaction with the T-box domain of TBX6 (<a href="/entry/602427">602427</a>). Functional analysis in transiently transfected C2C12 mouse myoblasts demonstrated significantly reduced transcriptional repression activity with the R80X mutant compared to wildtype RIPPLY2. The authors stated that they were unable to demonstrate a functional consequence of the c.240-4T-G mutation because of its location in the terminal exon splice site consensus sequence and the likely restriction of RIPPLY2 expression to embryogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25343988" 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=RCV000207041 OR RCV000888795 OR RCV002270022 OR RCV003390955" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000207041, RCV000888795, RCV002270022, RCV003390955" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000207041...</a>
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<p>For discussion of the c.240-4T-G transversion (c.240-4T-G, NM_001009994) in intron 3 of the RIPPLY2 gene that was found in compound heterozygous state in 2 brothers with spondylocostal dysostosis-6 (SCDO6; <a href="/entry/616566">616566</a>) by <a href="#5" class="mim-tip-reference" title="McInerney-Leo, A. M., Sparrow, D. B., Harris, J. E., Gardiner, B. B., Marshall, M. S., O'Reilly, V. C., Shi, H., Brown, M. A., Leo, P. J., Zankl, A., Dunwoodie, S. L., Duncan, E. L. <strong>Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects.</strong> Hum. Molec. Genet. 24: 1234-1242, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25343988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25343988</a>] [<a href="https://doi.org/10.1093/hmg/ddu534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25343988">McInerney-Leo et al. (2015)</a>, see <a href="#0001">609891.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25343988" 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>.0003 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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RIPPLY2, 1-BP DEL, 299T
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs864309489 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs864309489;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=rs864309489" 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=rs864309489" 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=RCV000202450 OR RCV000207167" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000202450, RCV000207167" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000202450...</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to Klippel-Feil syndrome (KFS; see <a href="/entry/214300">214300</a>) has not been confirmed.</p><p>In a 13.75-year-old Turkish boy with features of Klippel-Feil syndrome and situs inversus totalis, who was negative for mutation in genes associated with KFS, disorders of primary ciliary dyskinesia, heterotaxy, or segmentation defects of the vertebrae, <a href="#3" class="mim-tip-reference" title="Karaca, E., Yuregir, O. O., Bozdogen, S. T., Aslan, H., Pehlivan, D., Jhangiani, S. N., Akdemir, Z. C., Gambin, T., Bayram, Y., Atik, M. M., Erdin, S., Muzny, D., Gibbs, R. A., Lupski, J. R., The Baylor-Hopkins Center for Mendelian Genomics. <strong>Rare variants in the Notch signaling pathway describe a novel type of autosomal recessive Klippel-Feil syndrome.</strong> Am. J. Med. Genet. 167A: 2795-2799, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26238661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26238661</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26238661[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.37263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26238661">Karaca et al. (2015)</a> identified homozygosity for a 1-bp deletion (c.299delT, NM_001009994) in the RIPPLY2 gene, causing a frameshift within the conserved segment of the RIPPLY protein domain (Leu100fs). His unaffected first-cousin parents and an unaffected sib were heterozygous for the deletion. The proband had short stature, scoliosis, short neck with decreased mobility, and low posterior hairline, and imaging studies revealed fusion of the cervical vertebrae as well as situs inversus totalis. Other features included upward displacement of the scapula (Sprengel deformity), pectus excavatum of the upper sternum and pectus carinatum of the lower sternum, patent foramen ovale, and solitary kidney. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26238661" 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 id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Chan2007" class="mim-anchor"></a>
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Chan, T., Kondow, A., Hosoya, A., Hitachi, K., Yukita, A., Okabayashi, K., Nakamura, H., Ozawa, H., Kiyonari, H., Michiue, T., Ito, Y., Asashima, M.
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<strong>Ripply2 is essential for precise somite formation during mouse early development.</strong>
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FEBS Lett. 581: 2691-2696, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17531978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17531978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17531978" 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/j.febslet.2007.05.017" target="_blank">Full Text</a>]
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<a id="Gross2015" class="mim-anchor"></a>
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 9/22/2015.
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<a id="Karaca2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Karaca, E., Yuregir, O. O., Bozdogen, S. T., Aslan, H., Pehlivan, D., Jhangiani, S. N., Akdemir, Z. C., Gambin, T., Bayram, Y., Atik, M. M., Erdin, S., Muzny, D., Gibbs, R. A., Lupski, J. R., The Baylor-Hopkins Center for Mendelian Genomics.
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<strong>Rare variants in the Notch signaling pathway describe a novel type of autosomal recessive Klippel-Feil syndrome.</strong>
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Am. J. Med. Genet. 167A: 2795-2799, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26238661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26238661</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26238661[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=26238661" 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/ajmg.a.37263" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
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<a id="Kawamura2005" class="mim-anchor"></a>
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Kawamura, A., Koshida, S., Hijikata, H., Ohbayashi, A., Kondoh, H., Takada, S.
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<strong>Groucho-associated transcriptional repressor Ripply1 is required for proper transition from the presomitic mesoderm to somites.</strong>
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Dev. Cell 9: 735-744, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16326386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16326386</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16326386" 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/j.devcel.2005.09.021" target="_blank">Full Text</a>]
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<a id="McInerney-Leo2015" class="mim-anchor"></a>
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McInerney-Leo, A. M., Sparrow, D. B., Harris, J. E., Gardiner, B. B., Marshall, M. S., O'Reilly, V. C., Shi, H., Brown, M. A., Leo, P. J., Zankl, A., Dunwoodie, S. L., Duncan, E. L.
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<strong>Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects.</strong>
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Hum. Molec. Genet. 24: 1234-1242, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25343988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25343988</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25343988" 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/ddu534" target="_blank">Full Text</a>]
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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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Marla J. F. O'Neill - updated : 02/02/2016
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 9/25/2015<br>Matthew B. Gross - updated : 9/22/2015<br>Marla J. F. O'Neill - updated : 9/22/2015
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Creation Date:
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Patricia A. Hartz : 2/16/2006
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carol : 02/02/2016
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mgross : 9/25/2015<br>mgross : 9/22/2015<br>mgross : 9/22/2015<br>carol : 9/22/2015<br>alopez : 2/16/2006
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<strong>*</strong> 609891
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RIPPLY TRANSCRIPTIONAL REPRESSOR 2; RIPPLY2
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CHROMOSOME 6 OPEN READING FRAME 59; C6ORF59
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<strong><em>HGNC Approved Gene Symbol: RIPPLY2</em></strong>
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Cytogenetic location: 6q14.2
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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6q14.2
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</span>
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</td>
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<td>
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<span class="mim-font">
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?Spondylocostal dysostosis 6
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</span>
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</td>
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<td>
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<span class="mim-font">
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616566
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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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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<span class="mim-text-font">
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<p>By searching for sequences similar to that of zebrafish Ripply1 (300575), Kawamura et al. (2005) identified human RIPPLY2. The deduced 128-amino acid protein contains a WRPW tetrapeptide near its N terminus and a conserved domain of about 50 amino acids found in other Ripply proteins. In zebrafish embryos, Ripply2 was expressed in the paraxial mesoderm and was subsequently confined to the presomitic mesoderm. </p><p>Chan et al. (2007) found that Ripply2 was expressed in presomitic mesoderm in day-9.0 and -11.5 mouse embryos, concomitant with somite formation. </p>
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</span>
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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>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>Gross (2015) mapped the RIPPLY2 gene to chromosome 6q14.2 based on an alignment of the RIPPLY2 sequence (GenBank BC130460) with the genomic sequence (GRCh38).</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>Molecular Genetics</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><strong><em>Spondylocostal Dysostosis 6</em></strong></p><p>
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In 2 brothers with segmentation defects of the vertebrae (SCDO6; 616566), McInerney-Leo et al. (2015) identified compound heterozygosity for a nonsense mutation (R80X; 609891.0001) and a splice site mutation (c.240-4T-G; 609891.0002) in the RIPPLY2 gene that segregated with disease in the family. Analysis of in-house sequencing data from 991 individuals with unrelated disorders did not detect any with compound heterozygous variants in RIPPLY2. McInerney-Leo et al. (2015) noted that a rare variant (minor allele frequency less than 0.01) was detected in 1 of 1,982 alleles, thus the probability of 2 rare variants occurring by chance would be 2.54 x 10(-7), and the probability of both segregating appropriately within the family would be even lower. In addition, functional analysis demonstrated significantly reduced transcriptional repression activity with the R80X mutant compared to wildtype RIPPLY2. The authors stated that they were unable to demonstrate a functional consequence of the c.240-4T-G mutation because of its location in the terminal exon splice site consensus sequence and the likely restriction of RIPPLY2 expression to embryogenesis. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between mutation in the RIPPLY2 gene and Klippel-Feil syndrome (see 214300), see 609891.0003.</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>Chan et al. (2007) obtained Ripply2 -/- mice at the expected mendelian ratio, but all died soon after birth without breathing. At embryonic day 18, Ripply2 -/- mice had shortened tails, truncated body axis, and defects in vertebral bodies, intervertebral discs, and neural arches. Pedicles of neural arches were fused or missing. Ribs in Ripply2 -/- mice were fused and bifurcated and showed loss of symmetry about the left-right axis, and they were reduced in number. Skull and limbs appeared normal. Skeletal malformations observed in Ripply2 -/- mice appeared to be due to defective somite segmentation. Expression of Notch2 (600275) and Uncx4.1 was disrupted in Ripply2 -/- mice. Chan et al. (2007) concluded that RIPPLY2 is involved in somite segmentation and establishment of rostrocaudal polarity. </p><p>McInerney-Leo et al. (2015) analyzed the skeletal development of Ripply2 +/- mice at embryonic day 14.5 and observed that 1 of 33 embryos exhibited a slight vertebral defect (unilateral interruption of the lamina of S1), whereas all 40 wildtype embryos were normal. The authors concluded that loss of 1 Ripply1 allele did not cause vertebral defects with significant penetrance. Analysis of similar embryos exposed to short-term mild hypoxia during pregnancy revealed that 4 of 30 heterozygous embryos had mild defects, each involving a single vertebra, compared to 1 of 35 wildtype embryos; thus, hypoxia did not significantly increase the penetrance or severity of vertebral defects in Ripply2 +/- embryos. </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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<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>3 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 SPONDYLOCOSTAL DYSOSTOSIS 6, AUTOSOMAL RECESSIVE (1 family)</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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RIPPLY2, ARG80TER
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<br />
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SNP: rs201419367,
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gnomAD: rs201419367,
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ClinVar: RCV000207268, RCV000275086, RCV002270021
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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 2 brothers (family SKDP-10) with segmentation defects of the vertebrae (SCDO6; 616566), McInerney-Leo et al. (2015) identified compound heterozygosity for 2 mutations in the RIPPLY2 gene: a c.238A-T transversion (c.238A-T, NM_001009994) in exon 3 of the RIPPLY2 gene, resulting in an arg80-to-ter (R80X) substitution, and a c.240-4T-G transversion in intron 3 (609891.0002) at the 5-prime predicted splice acceptor site for exon 4. Their unaffected parents were each heterozygous for 1 of the mutations, as was the unaffected maternal grandmother, whereas their unaffected sister did not carry either of the mutations. McInerney-Leo et al. (2015) noted that the R80X mutation causes loss of 49 C-terminal amino acids, including the highly conserved Ripply homology domain required for direct protein-protein interaction with the T-box domain of TBX6 (602427). Functional analysis in transiently transfected C2C12 mouse myoblasts demonstrated significantly reduced transcriptional repression activity with the R80X mutant compared to wildtype RIPPLY2. The authors stated that they were unable to demonstrate a functional consequence of the c.240-4T-G mutation because of its location in the terminal exon splice site consensus sequence and the likely restriction of RIPPLY2 expression to embryogenesis. </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 SPONDYLOCOSTAL DYSOSTOSIS 6, AUTOSOMAL RECESSIVE (1 family)</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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RIPPLY2, IVS3AS, T-G, -4
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<br />
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SNP: rs370933531,
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gnomAD: rs370933531,
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ClinVar: RCV000207041, RCV000888795, RCV002270022, RCV003390955
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>For discussion of the c.240-4T-G transversion (c.240-4T-G, NM_001009994) in intron 3 of the RIPPLY2 gene that was found in compound heterozygous state in 2 brothers with spondylocostal dysostosis-6 (SCDO6; 616566) by McInerney-Leo et al. (2015), see 609891.0001. </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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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</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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RIPPLY2, 1-BP DEL, 299T
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<br />
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SNP: rs864309489,
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ClinVar: RCV000202450, RCV000207167
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>This variant is classified as a variant of unknown significance because its contribution to Klippel-Feil syndrome (KFS; see 214300) has not been confirmed.</p><p>In a 13.75-year-old Turkish boy with features of Klippel-Feil syndrome and situs inversus totalis, who was negative for mutation in genes associated with KFS, disorders of primary ciliary dyskinesia, heterotaxy, or segmentation defects of the vertebrae, Karaca et al. (2015) identified homozygosity for a 1-bp deletion (c.299delT, NM_001009994) in the RIPPLY2 gene, causing a frameshift within the conserved segment of the RIPPLY protein domain (Leu100fs). His unaffected first-cousin parents and an unaffected sib were heterozygous for the deletion. The proband had short stature, scoliosis, short neck with decreased mobility, and low posterior hairline, and imaging studies revealed fusion of the cervical vertebrae as well as situs inversus totalis. Other features included upward displacement of the scapula (Sprengel deformity), pectus excavatum of the upper sternum and pectus carinatum of the lower sternum, patent foramen ovale, and solitary kidney. </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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Chan, T., Kondow, A., Hosoya, A., Hitachi, K., Yukita, A., Okabayashi, K., Nakamura, H., Ozawa, H., Kiyonari, H., Michiue, T., Ito, Y., Asashima, M.
|
|
<strong>Ripply2 is essential for precise somite formation during mouse early development.</strong>
|
|
FEBS Lett. 581: 2691-2696, 2007.
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[PubMed: 17531978]
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[Full Text: https://doi.org/10.1016/j.febslet.2007.05.017]
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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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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 9/22/2015.
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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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Karaca, E., Yuregir, O. O., Bozdogen, S. T., Aslan, H., Pehlivan, D., Jhangiani, S. N., Akdemir, Z. C., Gambin, T., Bayram, Y., Atik, M. M., Erdin, S., Muzny, D., Gibbs, R. A., Lupski, J. R., The Baylor-Hopkins Center for Mendelian Genomics.
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<strong>Rare variants in the Notch signaling pathway describe a novel type of autosomal recessive Klippel-Feil syndrome.</strong>
|
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Am. J. Med. Genet. 167A: 2795-2799, 2015.
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[PubMed: 26238661]
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[Full Text: https://doi.org/10.1002/ajmg.a.37263]
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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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Kawamura, A., Koshida, S., Hijikata, H., Ohbayashi, A., Kondoh, H., Takada, S.
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<strong>Groucho-associated transcriptional repressor Ripply1 is required for proper transition from the presomitic mesoderm to somites.</strong>
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Dev. Cell 9: 735-744, 2005.
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[PubMed: 16326386]
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[Full Text: https://doi.org/10.1016/j.devcel.2005.09.021]
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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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McInerney-Leo, A. M., Sparrow, D. B., Harris, J. E., Gardiner, B. B., Marshall, M. S., O'Reilly, V. C., Shi, H., Brown, M. A., Leo, P. J., Zankl, A., Dunwoodie, S. L., Duncan, E. L.
|
|
<strong>Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects.</strong>
|
|
Hum. Molec. Genet. 24: 1234-1242, 2015.
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[PubMed: 25343988]
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[Full Text: https://doi.org/10.1093/hmg/ddu534]
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</p>
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</li>
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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 class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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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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Marla J. F. O'Neill - updated : 02/02/2016<br>Patricia A. Hartz - updated : 9/25/2015<br>Matthew B. Gross - updated : 9/22/2015<br>Marla J. F. O'Neill - updated : 9/22/2015
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</span>
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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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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Patricia A. Hartz : 2/16/2006
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<span class="text-nowrap mim-text-font">
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Edit History:
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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 : 02/02/2016<br>mgross : 9/25/2015<br>mgross : 9/22/2015<br>mgross : 9/22/2015<br>carol : 9/22/2015<br>alopez : 2/16/2006
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OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
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Thank you in advance for your generous support, <br />
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