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Entry
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- *609291 - SPROUTY-RELATED EVH1 DOMAIN-CONTAINING PROTEIN 1; SPRED1
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- OMIM
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<p>
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<span class="h4">*609291</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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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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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/609291">Table View</a>
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<a href="#references"><strong>References</strong></a>
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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 role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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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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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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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=ENSG00000166068;t=ENST00000299084" 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=161742" 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=609291" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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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=ENSG00000166068;t=ENST00000299084" 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_152594,XM_005254202,XM_047432199,XM_047432200,XM_047432201" 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_152594" 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=609291" 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 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 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=11601&isoform_id=11601_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/SPRED1" 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/21749543,22749221,31872019,57013078,116283592,119612774,187953573,187953575,444733325,530405473,2217300263,2217300265,2217300267,2462542949,2462542951,2462542953" 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/Q7Z699" 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 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=161742" 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=ENSG00000166068;t=ENST00000299084" 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=SPRED1" 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=SPRED1" 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+161742" 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/SPRED1" 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:161742" 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/161742" 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=chr15&hgg_gene=ENST00000299084.9&hgg_start=38252836&hgg_end=38357249&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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:20249" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:20249" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/spred1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=609291[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=609291[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/SPRED1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000166068" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=SPRED1" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=SPRED1" 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=SPRED1" 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="http://www.arup.utah.edu/database/SPRED1/SPRED1_welcome.php" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SPRED1&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/PA134897382" 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:20249" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0020767.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2150016" 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/SPRED1#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:2150016" 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/161742/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=161742" 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-040426-2338" 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=SPRED1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 703541007<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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609291
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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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SPROUTY-RELATED EVH1 DOMAIN-CONTAINING PROTEIN 1; SPRED1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<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=SPRED1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SPRED1</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>
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Cytogenetic location: <a href="/geneMap/15/83?start=-3&limit=10&highlight=83">15q14</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr15:38252836-38357249&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'})">15:38,252,836-38,357,249</a> </span>
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</em>
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</strong>
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<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">
|
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<span class="mim-font">
|
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<a href="/geneMap/15/83?start=-3&limit=10&highlight=83">
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15q14
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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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Legius syndrome
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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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<a href="/entry/611431"> 611431 </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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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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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<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">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/609291" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/609291" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</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>
|
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
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</span>
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</h4>
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<div>
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<p>SPRED1 is a member of the Sprouty (see SPRY1; <a href="/entry/602465">602465</a>)/SPRED family of proteins that regulate growth factor-induced activation of the MAP kinase cascade (see MAPK1, <a href="/entry/176948">176948</a>) (<a href="#8" class="mim-tip-reference" title="Nonami, A., Kato, R., Taniguchi, K., Yoshiga, D., Taketomi, T., Fukuyama, S., Harada, M., Sasaki, A., Yoshimura, A. <strong>Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells.</strong> J. Biol. Chem. 279: 52543-52551, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15465815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15465815</a>] [<a href="https://doi.org/10.1074/jbc.M405189200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15465815">Nonami et al., 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15465815" 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="#12" class="mim-tip-reference" title="Wakioka, T., Sasaki, A., Kato, R., Shouda, T., Matsumoto, A., Miyoshi, K., Tsuneoka, M., Komiya, S., Baron, R., Yoshimura, A. <strong>Spred is a Sprouty-related suppressor of Ras signalling.</strong> Nature 412: 647-651, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11493923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11493923</a>] [<a href="https://doi.org/10.1038/35088082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11493923">Wakioka et al. (2001)</a> cloned mouse Spred1 from an osteoclast cDNA library. The deduced 444-amino acid protein contains an N-terminal Enabled (ENA; <a href="/entry/609061">609061</a>)/VASP (<a href="/entry/601703">601703</a>) homology-1 (EVH1) domain, a central KIT (<a href="/entry/164920">164920</a>)-binding domain (KBD), and a C-terminal SPRY domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11493923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using Northern blot analysis, <a href="#6" class="mim-tip-reference" title="Kato, R., Nonami, A., Taketomi, T., Wakioka, T., Kuroiwa, A., Matsuda, Y., Yoshimura, A. <strong>Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation.</strong> Biochem. Biophys. Res. Commun. 302: 767-772, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12646235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12646235</a>] [<a href="https://doi.org/10.1016/s0006-291x(03)00259-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12646235">Kato et al. (2003)</a> detected Spred1 expression in mouse brain, kidney, and colon, but not in any other tissues examined. <a href="#8" class="mim-tip-reference" title="Nonami, A., Kato, R., Taniguchi, K., Yoshiga, D., Taketomi, T., Fukuyama, S., Harada, M., Sasaki, A., Yoshimura, A. <strong>Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells.</strong> J. Biol. Chem. 279: 52543-52551, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15465815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15465815</a>] [<a href="https://doi.org/10.1074/jbc.M405189200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15465815">Nonami et al. (2004)</a> found Spred1 highly expressed in interleukin-3 (IL3; <a href="/entry/147740">147740</a>)-dependent mouse hematopoietic cell lines and bone marrow-derived mast cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12646235+15465815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The SPRED1 protein has a molecular mass of 50 kD and contains 444 amino acids (review by <a href="#3" class="mim-tip-reference" title="Brems, H., Pasmant, E., Van Minkelen, R., Wimmer, K., Upadhyaya, M., Legius, E., Messiaen, L. <strong>Review and update of SPRED1 mutations causing Legius syndrome.</strong> Hum. Mutat. 33: 1538-1546, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22753041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22753041</a>] [<a href="https://doi.org/10.1002/humu.22152" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22753041">Brems et al., 2012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22753041" 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="Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K. Kato, R., Somers, R., Messiaen, L., De Schepper, S., Fryns, J.-P., Cools, J., Marynen, P., Thomas, G., Yoshimura, A., Legius, E. <strong>Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. (Letter)</strong> Nature Genet. 39: 1120-1126, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704776</a>] [<a href="https://doi.org/10.1038/ng2113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17704776">Brems et al. (2007)</a> noted that the SPRED1 gene contains 8 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17704776" 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>By genomic sequence analysis, <a href="#6" class="mim-tip-reference" title="Kato, R., Nonami, A., Taketomi, T., Wakioka, T., Kuroiwa, A., Matsuda, Y., Yoshimura, A. <strong>Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation.</strong> Biochem. Biophys. Res. Commun. 302: 767-772, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12646235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12646235</a>] [<a href="https://doi.org/10.1016/s0006-291x(03)00259-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12646235">Kato et al. (2003)</a> mapped the SPRED1 gene to chromosome 15q13.2. They mapped the mouse Spred1 gene to chromosome 2E5 using FISH. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12646235" 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="#12" class="mim-tip-reference" title="Wakioka, T., Sasaki, A., Kato, R., Shouda, T., Matsumoto, A., Miyoshi, K., Tsuneoka, M., Komiya, S., Baron, R., Yoshimura, A. <strong>Spred is a Sprouty-related suppressor of Ras signalling.</strong> Nature 412: 647-651, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11493923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11493923</a>] [<a href="https://doi.org/10.1038/35088082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11493923">Wakioka et al. (2001)</a> found that mammalian Spred1 was phosphorylated in response to several growth factors, and efficient phosphorylation required the KBD domain. Overexpression of Spred1 inhibited NGF (<a href="/entry/162030">162030</a>)-induced neurite differentiation in rat PC12 cells, and both the EVH1 and SPRY domains were essential for the suppression. <a href="#12" class="mim-tip-reference" title="Wakioka, T., Sasaki, A., Kato, R., Shouda, T., Matsumoto, A., Miyoshi, K., Tsuneoka, M., Komiya, S., Baron, R., Yoshimura, A. <strong>Spred is a Sprouty-related suppressor of Ras signalling.</strong> Nature 412: 647-651, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11493923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11493923</a>] [<a href="https://doi.org/10.1038/35088082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11493923">Wakioka et al. (2001)</a> presented evidence that Spred1 and Spred2 (<a href="/entry/609292">609292</a>) could regulate differentiation in rat neuronal cells and mouse myocytes by inhibiting activation of MAP kinase. Inhibition appeared to occur through the formation of a Spred-Ras (<a href="/entry/190020">190020</a>) complex that inhibited activation of MAP kinase by suppressing phosphorylation and activation of Raf (see RAF1; <a href="/entry/164760">164760</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11493923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Kato, R., Nonami, A., Taketomi, T., Wakioka, T., Kuroiwa, A., Matsuda, Y., Yoshimura, A. <strong>Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation.</strong> Biochem. Biophys. Res. Commun. 302: 767-772, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12646235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12646235</a>] [<a href="https://doi.org/10.1016/s0006-291x(03)00259-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12646235">Kato et al. (2003)</a> found that mouse Spred1 coprecipitated with and was phosphorylated by a constitutively activated Kit mutant. The KBD was required for Kit binding, but suppression of growth factor-induced MAP kinase required the SPRY domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12646235" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Nonami, A., Kato, R., Taniguchi, K., Yoshiga, D., Taketomi, T., Fukuyama, S., Harada, M., Sasaki, A., Yoshimura, A. <strong>Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells.</strong> J. Biol. Chem. 279: 52543-52551, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15465815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15465815</a>] [<a href="https://doi.org/10.1074/jbc.M405189200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15465815">Nonami et al. (2004)</a> found that mouse Spred1 negatively regulated hematopoiesis by suppressing stem cell factor (KITLG; <a href="/entry/184745">184745</a>)- and IL3-induced ERK (see MAPK3; <a href="/entry/601795">601795</a>) activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15465815" 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>MicroRNAs, such as MIR126 (<a href="/entry/611767">611767</a>), downregulate mRNA expression by binding to short complementary sequences in the 3-prime UTRs of target mRNAs. <a href="#13" class="mim-tip-reference" title="Wang, S., Aurora, A. B., Johnson, B. A., Qi, X., McAnally, J., Hill, J. A., Richardson, J. A., Bassel-Duby, R., Olson, E. N. <strong>The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis.</strong> Dev. Cell 15: 261-271, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18694565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18694565</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18694565[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.devcel.2008.07.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18694565">Wang et al. (2008)</a> found that knockout of Mir126 in mice caused severe defects in vascularization. Using microarray analysis, they showed that endothelial cells from Mir126 -/- kidneys had elevated levels of Spred1, as well as numerous other genes involved in angiogenesis, cell adhesion, inflammatory/cytokine signaling, and cell cycle control. Real-time PCR and Western blot analysis confirmed upregulation of Spred1 in Mir126 -/- endothelial cells. <a href="#13" class="mim-tip-reference" title="Wang, S., Aurora, A. B., Johnson, B. A., Qi, X., McAnally, J., Hill, J. A., Richardson, J. A., Bassel-Duby, R., Olson, E. N. <strong>The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis.</strong> Dev. Cell 15: 261-271, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18694565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18694565</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18694565[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.devcel.2008.07.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18694565">Wang et al. (2008)</a> identified a sequence complementary to the seed sequence of Mir126 in the 3-prime UTR of Spred1 mRNA, and they confirmed that Mir126 downregulated expression of a reporter gene that included the Spred1 3-prime UTR. Further experiments revealed that Mir126 augmented angiogenesis by diminishing the inhibitory influence of Spred1 on the MAP kinase pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18694565" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Hollander, J. A., Im, H.-I., Amelio, A. L., Kocerha, J., Bali, P., Lu, Q., Willoughby, D., Wahlestedt, C., Conkright, M. D., Kenny, P. J. <strong>Striatal microRNA controls cocaine intake through CREB signalling.</strong> Nature 466: 197-202, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20613834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20613834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20613834[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20613834">Hollander et al. (2010)</a> found that miR212 (<a href="/entry/613487">613487</a>) was upregulated in the dorsal striatum of rats with a history of extended access to cocaine. Striatal miR212 decreased responsiveness to the motivational properties of cocaine by markedly amplifying the stimulatory effects of the drug on Creb (<a href="/entry/123810">123810</a>) signaling. Studies in rats and HEK cells showed that amplification of CREB signaling occurred through miR212-enhanced RAF1 activity, resulting in adenylyl cyclase sensitization and increased expression of the essential Creb coactivator TORC (see CRTC1; <a href="/entry/607536">607536</a>). miR212 activated RAF1, at least in part, through repression of SPRED1. <a href="#4" class="mim-tip-reference" title="Hollander, J. A., Im, H.-I., Amelio, A. L., Kocerha, J., Bali, P., Lu, Q., Willoughby, D., Wahlestedt, C., Conkright, M. D., Kenny, P. J. <strong>Striatal microRNA controls cocaine intake through CREB signalling.</strong> Nature 466: 197-202, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20613834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20613834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20613834[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20613834">Hollander et al. (2010)</a> concluded that striatal miR212 signaling has a key role in determining vulnerability to cocaine addiction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20613834" 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>To identify driver genes in mucosal melanoma, <a href="#1" class="mim-tip-reference" title="Ablain, J., Xu, M., Rothschild, H., Jordan, R. C., Mito, J. K., Daniels, B. H., Bell, C. F., Joseph, N. M., Wu, H., Bastian, B. C., Zon, L. I., Yeh, I. <strong>Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma.</strong> Science 362: 1055-1060, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30385465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30385465</a>] [<a href="https://doi.org/10.1126/science.aau6509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30385465">Ablain et al. (2018)</a> sequenced hundreds of cancer-related genes in 43 human mucosal melanomas (see <a href="/entry/155600">155600</a>), cataloging point mutations, amplifications, and deletions. The SPRED1 gene, which encodes a negative regulator of mitogen-activated protein kinase (MAPK) signaling, was inactivated in 37% of the tumors. Four distinct genotypes were associated with SPRED1 loss. Using a rapid, tissue-specific CRISPR technique to model these genotypes in zebrafish, <a href="#1" class="mim-tip-reference" title="Ablain, J., Xu, M., Rothschild, H., Jordan, R. C., Mito, J. K., Daniels, B. H., Bell, C. F., Joseph, N. M., Wu, H., Bastian, B. C., Zon, L. I., Yeh, I. <strong>Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma.</strong> Science 362: 1055-1060, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30385465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30385465</a>] [<a href="https://doi.org/10.1126/science.aau6509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30385465">Ablain et al. (2018)</a> found that SPRED1 functions as a tumor suppressor, particularly in the context of KIT (<a href="/entry/164920">164920</a>) mutations. SPRED1 knockdown caused MAPK activation, increased cell proliferation, and conferred resistance to drugs inhibiting KIT tyrosine kinase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30385465" 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>In a review of the molecular genetics of Legius syndrome (LGSS; <a href="/entry/611431">611431</a>), <a href="#3" class="mim-tip-reference" title="Brems, H., Pasmant, E., Van Minkelen, R., Wimmer, K., Upadhyaya, M., Legius, E., Messiaen, L. <strong>Review and update of SPRED1 mutations causing Legius syndrome.</strong> Hum. Mutat. 33: 1538-1546, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22753041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22753041</a>] [<a href="https://doi.org/10.1002/humu.22152" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22753041">Brems et al. (2012)</a> noted that SPRED1 mutations result in a loss of protein function and an inability of SPRED1 to downregulate the RAS-MAPK pathway. There are no apparent genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22753041" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 5 unrelated families with Legius syndrome, <a href="#2" class="mim-tip-reference" title="Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K. Kato, R., Somers, R., Messiaen, L., De Schepper, S., Fryns, J.-P., Cools, J., Marynen, P., Thomas, G., Yoshimura, A., Legius, E. <strong>Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. (Letter)</strong> Nature Genet. 39: 1120-1126, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704776</a>] [<a href="https://doi.org/10.1038/ng2113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17704776">Brems et al. (2007)</a> identified 4 different heterozygous mutations in the SPRED1 gene (<a href="#0001">609291.0001</a>-<a href="#0004">609291.0004</a>). Screening of 86 additional patients who had undergone NF1 (<a href="/entry/162200">162200</a>) testing with negative results identified 7 additional SPRED1 mutations (see, e.g., <a href="#0005">609291.0005</a>). Melanocyte culture studies demonstrated that SPRED1 -/- cells had higher MAPK and ERK phosphorylation compared to heterozygous or wildtype cells. Further studies indicated that the mutations resulted in loss of function and that mutant SPRED1 proteins had lost their ability to inhibit RAF-MEK (see <a href="/entry/176872">176872</a>)-ERK signaling. Haploinsufficiency appeared to be the mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17704776" 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="#9" class="mim-tip-reference" title="Pasmant, E., Sabbagh, A., Hanna, N., Masliah-Planchon, J., Jolly, E., Goussard, P., Ballerini, P., Cartault, F., Barbarot, S., Landman-Parker, J., Soufir, N., Parfait, B., Vidaud, M., Wolkenstein, P., Vidaud, D., France, R. N. F. <strong>SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype.</strong> J. Med. Genet. 46: 425-430, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19366998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19366998</a>] [<a href="https://doi.org/10.1136/jmg.2008.065243" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19366998">Pasmant et al. (2009)</a> identified 5 truncating mutations in the SPRED1 gene (see, e.g., <a href="#0005">609291.0005</a> and <a href="#0006">609291.0006</a>) in affected members of 5 unrelated French families with Legius syndrome. The phenotype included a high prevalence of cafe-au-lait spots and axillary and groin freckling. Other variable features included lipomas and learning disabilities. Facial dysmorphism was not observed. As none of the patients had neurofibromas or Lisch nodules, <a href="#9" class="mim-tip-reference" title="Pasmant, E., Sabbagh, A., Hanna, N., Masliah-Planchon, J., Jolly, E., Goussard, P., Ballerini, P., Cartault, F., Barbarot, S., Landman-Parker, J., Soufir, N., Parfait, B., Vidaud, M., Wolkenstein, P., Vidaud, D., France, R. N. F. <strong>SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype.</strong> J. Med. Genet. 46: 425-430, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19366998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19366998</a>] [<a href="https://doi.org/10.1136/jmg.2008.065243" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19366998">Pasmant et al. (2009)</a> suggested that the condition be named 'Legius syndrome.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19366998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Spurlock, G., Bennett, E., Chuzhanova, N., Thomas, N., Jim, H.-P., Side, L., Davies, S., Haan, E., Kerr, B., Huson, S. M., Upadhyaya, M. <strong>SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype.</strong> J. Med. Genet. 46: 431-437, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19443465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19443465</a>] [<a href="https://doi.org/10.1136/jmg.2008.065474" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19443465">Spurlock et al. (2009)</a> identified 6 different SPRED1 mutations (see, e.g., <a href="#0007">609291.0007</a> and <a href="#0008">609291.0008</a>) in 6 of 85 probands with a mild NF1 phenotype and no neurofibromas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19443465" 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="#7" class="mim-tip-reference" title="Laycock-van Spyk, S., Jim, H. P., Thomas, L., Spurlock, G., Fares, L., Palmer-Smith, S., Kini, U., Saggar, A., Patton, M., Mautner, V., Pilz, D. T., Upadhyaya, M. <strong>Identification of five novel SPRED1 germline mutations in Legius syndrome. (Letter)</strong> Clin. Genet. 80: 93-96, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21649642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21649642</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01618.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21649642">Laycock-van Spyk et al. (2011)</a> identified 6 different heterozygous nonsense or frameshift mutations in the SPRED1 gene in 6 of 115 patients with an NF1-like syndrome but without mutations in the NF1 gene. Combining their data with those from their earlier study (<a href="#11" class="mim-tip-reference" title="Spurlock, G., Bennett, E., Chuzhanova, N., Thomas, N., Jim, H.-P., Side, L., Davies, S., Haan, E., Kerr, B., Huson, S. M., Upadhyaya, M. <strong>SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype.</strong> J. Med. Genet. 46: 431-437, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19443465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19443465</a>] [<a href="https://doi.org/10.1136/jmg.2008.065474" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19443465">Spurlock et al., 2009</a>), <a href="#7" class="mim-tip-reference" title="Laycock-van Spyk, S., Jim, H. P., Thomas, L., Spurlock, G., Fares, L., Palmer-Smith, S., Kini, U., Saggar, A., Patton, M., Mautner, V., Pilz, D. T., Upadhyaya, M. <strong>Identification of five novel SPRED1 germline mutations in Legius syndrome. (Letter)</strong> Clin. Genet. 80: 93-96, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21649642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21649642</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01618.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21649642">Laycock-van Spyk et al. (2011)</a> estimated that SPRED1 mutations are found in about 6% of such patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19443465+21649642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Spencer, E., Davis, J., Mikhail, F., Fu, C., Vijzelaar, R., Zackai, E. H., Feret, H., Meyn, M. S., Shugar, A., Bellus, G., Kocsis, K., Kivirikko, S., Poyhonen, M., Messiaen, L. <strong>Identification of SPRED1 deletions using RT-PCR, multiplex ligation-dependent probe amplification and quantitative PCR.</strong> Am. J. Med. Genet. 155A: 1352-1359, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21548021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21548021</a>] [<a href="https://doi.org/10.1002/ajmg.a.33894" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21548021">Spencer et al. (2011)</a> used multiplex ligation-dependent probe amplification (MLPA) to screen 510 NF1-negative patients with multiple cafe-au-lait spots with or without freckling and no other signs of NF1 for deletions in the SPRED1 gene. Four different deletions were detected, including 2 that segregated with the phenotype in 2 families and 2 that were apparently sporadic. All the deletions had different breakpoints, with 1 including 2 neighboring genes. Point mutations or 1- to 4-bp insertion/deletion mutations were found in 36 of the 510 individuals. Thus, deletions accounted for about 10% of the 40 detected SPRED1 mutations in this cohort, suggesting that dosage analysis of this gene should be performed in candidate patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21548021" 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="#5" class="mim-tip-reference" title="Inoue, H., Kato, R., Fukuyama, S., Nonami, A., Taniguchi, K., Matsumoto, K., Nakano, T., Tsuda, M., Matsumura, M., Kubo, M., Ishikawa, F., Moon, B., Takatsu, K., Nakanishi, Y., Yoshimura, A. <strong>Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness.</strong> J. Exp. Med. 201: 73-82, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15630138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15630138</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15630138[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/10.1084/jem.20040616" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15630138">Inoue et al. (2005)</a> generated healthy and fertile Spred1-deficient mice by targeting exons encoding the KIT-binding and Sprouty-related domains. Spred1-deficient mice showed exaggerated allergen-induced airway hyperresponsiveness, eosinophilia, and mucus production in an allergic asthma model. They also had increased responsiveness, in terms of ERK signaling, to Il5 (<a href="/entry/147850">147850</a>) with subsequent overexpression of Il13 (<a href="/entry/147683">147683</a>) in eosinophils. <a href="#5" class="mim-tip-reference" title="Inoue, H., Kato, R., Fukuyama, S., Nonami, A., Taniguchi, K., Matsumoto, K., Nakano, T., Tsuda, M., Matsumura, M., Kubo, M., Ishikawa, F., Moon, B., Takatsu, K., Nakanishi, Y., Yoshimura, A. <strong>Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness.</strong> J. Exp. Med. 201: 73-82, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15630138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15630138</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15630138[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/10.1084/jem.20040616" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15630138">Inoue et al. (2005)</a> proposed that SPRED1 downregulation in the airway has a role in prolonged airway eosinophilia and asthma phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15630138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121434312 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434312;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/rs121434312?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=rs121434312" 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=rs121434312" 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=RCV000001882 OR RCV001813180 OR RCV002225255 OR RCV002273919 OR RCV002336072" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001882, RCV001813180, RCV002225255, RCV002273919, RCV002336072" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001882...</a>
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<p>In affected members of 2 unrelated families with autosomal dominant Legius syndrome (LGSS; <a href="/entry/611431">611431</a>), <a href="#2" class="mim-tip-reference" title="Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K. Kato, R., Somers, R., Messiaen, L., De Schepper, S., Fryns, J.-P., Cools, J., Marynen, P., Thomas, G., Yoshimura, A., Legius, E. <strong>Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. (Letter)</strong> Nature Genet. 39: 1120-1126, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704776</a>] [<a href="https://doi.org/10.1038/ng2113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17704776">Brems et al. (2007)</a> identified a heterozygous 349C-T transition in exon 4 of the SPRED1 gene, resulting in an arg117-to-ter (R117X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17704776" 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>.0002 LEGIUS SYNDROME</strong>
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SPRED1, ARG24TER
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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> rs121434313 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434313;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/rs121434313?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=rs121434313" 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=rs121434313" 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=RCV000001883 OR RCV001172084" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001883, RCV001172084" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001883...</a>
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<p>In affected members of a family with Legius syndrome (LGSS; <a href="/entry/611431">611431</a>), <a href="#2" class="mim-tip-reference" title="Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K. Kato, R., Somers, R., Messiaen, L., De Schepper, S., Fryns, J.-P., Cools, J., Marynen, P., Thomas, G., Yoshimura, A., Legius, E. <strong>Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. (Letter)</strong> Nature Genet. 39: 1120-1126, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704776</a>] [<a href="https://doi.org/10.1038/ng2113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17704776">Brems et al. (2007)</a> identified a heterozygous 70C-T transition in exon 3 of the SPRED1 gene, resulting in an arg24-to-ter (R24X) substitution. The R24X mutation was present in normal skin and melanocytes from a cafe-au-lait spot of 1 patient, but melanocytes from the cafe-au-lait spot showed an additional somatic SPRED1 mutation. The 2 mutations were located on different alleles, suggesting that SPRED1 function was completely absent in these cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17704776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0003" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0003 LEGIUS SYNDROME</strong>
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SPRED1, IVS5DS, G-A, +1
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1566868058 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1566868058;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=rs1566868058" 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=rs1566868058" 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=RCV000001884" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001884" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001884</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In affected members of a family with Legius syndrome (LGSS; <a href="/entry/611431">611431</a>), <a href="#2" class="mim-tip-reference" title="Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K. Kato, R., Somers, R., Messiaen, L., De Schepper, S., Fryns, J.-P., Cools, J., Marynen, P., Thomas, G., Yoshimura, A., Legius, E. <strong>Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. (Letter)</strong> Nature Genet. 39: 1120-1126, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704776</a>] [<a href="https://doi.org/10.1038/ng2113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17704776">Brems et al. (2007)</a> identified a heterozygous G-to-A transition in the donor splice site of intron 5 (423+1G-A), resulting in the skipping of exon 5 and an out-of-frame deletion of 47 nucleotides at the mRNA level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17704776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0004" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0004 LEGIUS SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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SPRED1, GLN215TER
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434314 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434314;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=rs121434314" 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=rs121434314" 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=RCV000001885" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001885" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001885</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with Legius syndrome (LGSS; <a href="/entry/611431">611431</a>), <a href="#2" class="mim-tip-reference" title="Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K. Kato, R., Somers, R., Messiaen, L., De Schepper, S., Fryns, J.-P., Cools, J., Marynen, P., Thomas, G., Yoshimura, A., Legius, E. <strong>Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. (Letter)</strong> Nature Genet. 39: 1120-1126, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704776</a>] [<a href="https://doi.org/10.1038/ng2113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17704776">Brems et al. (2007)</a> identified a heterozygous 643C-T transition in exon 7 of the SPRED1 gene, resulting in a gln215-to-ter (Q215X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17704776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 LEGIUS SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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SPRED1, ARG64TER
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</div>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434315 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434315;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=rs121434315" 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=rs121434315" 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=RCV000001886 OR RCV003320544" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001886, RCV003320544" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001886...</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p>In an individual with Legius syndrome (LGSS; <a href="/entry/611431">611431</a>), <a href="#2" class="mim-tip-reference" title="Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K. Kato, R., Somers, R., Messiaen, L., De Schepper, S., Fryns, J.-P., Cools, J., Marynen, P., Thomas, G., Yoshimura, A., Legius, E. <strong>Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. (Letter)</strong> Nature Genet. 39: 1120-1126, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704776</a>] [<a href="https://doi.org/10.1038/ng2113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17704776">Brems et al. (2007)</a> identified a heterozygous 190C-T transition in exon 3 of the SPRED1 gene, resulting in an arg64-to-ter (R64X) substitution. The patient had multiple cafe-au-lait spots and did not have a NF1 mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17704776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a French family with Legius syndrome, <a href="#9" class="mim-tip-reference" title="Pasmant, E., Sabbagh, A., Hanna, N., Masliah-Planchon, J., Jolly, E., Goussard, P., Ballerini, P., Cartault, F., Barbarot, S., Landman-Parker, J., Soufir, N., Parfait, B., Vidaud, M., Wolkenstein, P., Vidaud, D., France, R. N. F. <strong>SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype.</strong> J. Med. Genet. 46: 425-430, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19366998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19366998</a>] [<a href="https://doi.org/10.1136/jmg.2008.065243" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19366998">Pasmant et al. (2009)</a> identified the same R64X mutation. The phenotype included a high prevalence of cafe-au-lait spots and axillary and groin freckling. Two patients had a lipoma and another had learning disability. None had neurofibromas or Lisch nodules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19366998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 LEGIUS SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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SPRED1, GLN213TER
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434316 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434316;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=rs121434316" 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=rs121434316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001887" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001887" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001887</a>
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<p>In affected members of a French family with Legius syndrome (LGSS; <a href="/entry/611431">611431</a>), <a href="#9" class="mim-tip-reference" title="Pasmant, E., Sabbagh, A., Hanna, N., Masliah-Planchon, J., Jolly, E., Goussard, P., Ballerini, P., Cartault, F., Barbarot, S., Landman-Parker, J., Soufir, N., Parfait, B., Vidaud, M., Wolkenstein, P., Vidaud, D., France, R. N. F. <strong>SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype.</strong> J. Med. Genet. 46: 425-430, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19366998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19366998</a>] [<a href="https://doi.org/10.1136/jmg.2008.065243" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19366998">Pasmant et al. (2009)</a> identified a heterozygous 637C-T transition in exon 7 of the SPRED1 gene, resulting in a gln213-to-ter (Q213X) substitution. The phenotype included a high prevalence of cafe-au-lait spots and axillary and groin freckling. One patient had a learning disability. None had neurofibromas or Lisch nodules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19366998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 LEGIUS SYNDROME</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434317 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434317;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=rs121434317" 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=rs121434317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001888" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001888" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001888</a>
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<p>In a father and son with Legius syndrome (LGSS; <a href="/entry/611431">611431</a>), <a href="#11" class="mim-tip-reference" title="Spurlock, G., Bennett, E., Chuzhanova, N., Thomas, N., Jim, H.-P., Side, L., Davies, S., Haan, E., Kerr, B., Huson, S. M., Upadhyaya, M. <strong>SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype.</strong> J. Med. Genet. 46: 431-437, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19443465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19443465</a>] [<a href="https://doi.org/10.1136/jmg.2008.065474" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19443465">Spurlock et al. (2009)</a> identified a heterozygous 784A-T transversion in exon 8 of the SPRED1 gene, resulting in an arg262-to-ter (R262X) substitution. Both had cafe-au-lait spots and axillary freckling, but no neurofibromas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19443465" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 LEGIUS SYNDROME</strong>
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SPRED1, VAL44ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434318 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434318;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=rs121434318" 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=rs121434318" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001889" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001889" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001889</a>
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<p>In 4 affected members of a 3-generation family with Legius syndrome (LGSS; <a href="/entry/611431">611431</a>), <a href="#11" class="mim-tip-reference" title="Spurlock, G., Bennett, E., Chuzhanova, N., Thomas, N., Jim, H.-P., Side, L., Davies, S., Haan, E., Kerr, B., Huson, S. M., Upadhyaya, M. <strong>SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype.</strong> J. Med. Genet. 46: 431-437, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19443465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19443465</a>] [<a href="https://doi.org/10.1136/jmg.2008.065474" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19443465">Spurlock et al. (2009)</a> identified a heterozygous 131T-A transversion in exon 3 of the SPRED1 gene, resulting in a val44-to-asp (V55D) substitution in a highly conserved residue. All had cafe-au-lait spots, but no neurofibromas. The father had a head circumference in the 90th percentile, but all other family members had a normal head size. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19443465" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<strong>.0009 LEGIUS SYNDROME</strong>
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SPRED1, 2-BP DEL, 1045AG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1566876941 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1566876941;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=rs1566876941" 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=rs1566876941" 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=RCV000023764 OR RCV002399334" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023764, RCV002399334" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023764...</a>
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<p>In a mother and her 4 children, all with Legius syndrome (LGSS; <a href="/entry/611431">611431</a>), <a href="#7" class="mim-tip-reference" title="Laycock-van Spyk, S., Jim, H. P., Thomas, L., Spurlock, G., Fares, L., Palmer-Smith, S., Kini, U., Saggar, A., Patton, M., Mautner, V., Pilz, D. T., Upadhyaya, M. <strong>Identification of five novel SPRED1 germline mutations in Legius syndrome. (Letter)</strong> Clin. Genet. 80: 93-96, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21649642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21649642</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01618.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21649642">Laycock-van Spyk et al. (2011)</a> identified a heterozygous 2-bp deletion (1045delAG) in exon 7 of the SPRED1 gene, resulting in a frameshift and premature termination. The mother had perioral and ocular hyperpigmentation, hypertelorism, mild ptosis, and hypotonia. All patients had decreased IQ or learning difficulties. None had Lisch nodules or neurofibromas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21649642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Ablain2018" class="mim-anchor"></a>
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Ablain, J., Xu, M., Rothschild, H., Jordan, R. C., Mito, J. K., Daniels, B. H., Bell, C. F., Joseph, N. M., Wu, H., Bastian, B. C., Zon, L. I., Yeh, I.
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<strong>Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma.</strong>
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Science 362: 1055-1060, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30385465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30385465</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30385465" 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/10.1126/science.aau6509" target="_blank">Full Text</a>]
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Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K. Kato, R., Somers, R., Messiaen, L., De Schepper, S., Fryns, J.-P., Cools, J., Marynen, P., Thomas, G., Yoshimura, A., Legius, E.
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<strong>Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. (Letter)</strong>
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Nature Genet. 39: 1120-1126, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17704776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng2113" target="_blank">Full Text</a>]
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<a id="Brems2012" class="mim-anchor"></a>
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Brems, H., Pasmant, E., Van Minkelen, R., Wimmer, K., Upadhyaya, M., Legius, E., Messiaen, L.
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<strong>Review and update of SPRED1 mutations causing Legius syndrome.</strong>
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Hum. Mutat. 33: 1538-1546, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22753041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22753041</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22753041" 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/humu.22152" target="_blank">Full Text</a>]
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Hollander, J. A., Im, H.-I., Amelio, A. L., Kocerha, J., Bali, P., Lu, Q., Willoughby, D., Wahlestedt, C., Conkright, M. D., Kenny, P. J.
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<strong>Striatal microRNA controls cocaine intake through CREB signalling.</strong>
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Nature 466: 197-202, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20613834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20613834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20613834[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=20613834" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature09202" target="_blank">Full Text</a>]
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<a id="Inoue2005" class="mim-anchor"></a>
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Inoue, H., Kato, R., Fukuyama, S., Nonami, A., Taniguchi, K., Matsumoto, K., Nakano, T., Tsuda, M., Matsumura, M., Kubo, M., Ishikawa, F., Moon, B., Takatsu, K., Nakanishi, Y., Yoshimura, A.
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<strong>Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness.</strong>
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J. Exp. Med. 201: 73-82, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15630138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15630138</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15630138[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=15630138" 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/10.1084/jem.20040616" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Kato2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kato, R., Nonami, A., Taketomi, T., Wakioka, T., Kuroiwa, A., Matsuda, Y., Yoshimura, A.
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|
<strong>Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation.</strong>
|
|
Biochem. Biophys. Res. Commun. 302: 767-772, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12646235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12646235</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12646235" 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/s0006-291x(03)00259-6" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Laycock-van Spyk2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Laycock-van Spyk, S., Jim, H. P., Thomas, L., Spurlock, G., Fares, L., Palmer-Smith, S., Kini, U., Saggar, A., Patton, M., Mautner, V., Pilz, D. T., Upadhyaya, M.
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<strong>Identification of five novel SPRED1 germline mutations in Legius syndrome. (Letter)</strong>
|
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Clin. Genet. 80: 93-96, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21649642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21649642</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21649642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2010.01618.x" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Nonami2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nonami, A., Kato, R., Taniguchi, K., Yoshiga, D., Taketomi, T., Fukuyama, S., Harada, M., Sasaki, A., Yoshimura, A.
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<strong>Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells.</strong>
|
|
J. Biol. Chem. 279: 52543-52551, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15465815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15465815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15465815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M405189200" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Pasmant2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Pasmant, E., Sabbagh, A., Hanna, N., Masliah-Planchon, J., Jolly, E., Goussard, P., Ballerini, P., Cartault, F., Barbarot, S., Landman-Parker, J., Soufir, N., Parfait, B., Vidaud, M., Wolkenstein, P., Vidaud, D., France, R. N. F.
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<strong>SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype.</strong>
|
|
J. Med. Genet. 46: 425-430, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19366998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19366998</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19366998" 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/10.1136/jmg.2008.065243" target="_blank">Full Text</a>]
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Spencer2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Spencer, E., Davis, J., Mikhail, F., Fu, C., Vijzelaar, R., Zackai, E. H., Feret, H., Meyn, M. S., Shugar, A., Bellus, G., Kocsis, K., Kivirikko, S., Poyhonen, M., Messiaen, L.
|
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<strong>Identification of SPRED1 deletions using RT-PCR, multiplex ligation-dependent probe amplification and quantitative PCR.</strong>
|
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Am. J. Med. Genet. 155A: 1352-1359, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21548021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21548021</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21548021" 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.33894" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Spurlock2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Spurlock, G., Bennett, E., Chuzhanova, N., Thomas, N., Jim, H.-P., Side, L., Davies, S., Haan, E., Kerr, B., Huson, S. M., Upadhyaya, M.
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<strong>SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype.</strong>
|
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J. Med. Genet. 46: 431-437, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19443465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19443465</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19443465" 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/10.1136/jmg.2008.065474" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Wakioka2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wakioka, T., Sasaki, A., Kato, R., Shouda, T., Matsumoto, A., Miyoshi, K., Tsuneoka, M., Komiya, S., Baron, R., Yoshimura, A.
|
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<strong>Spred is a Sprouty-related suppressor of Ras signalling.</strong>
|
|
Nature 412: 647-651, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11493923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11493923</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11493923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/35088082" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Wang2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, S., Aurora, A. B., Johnson, B. A., Qi, X., McAnally, J., Hill, J. A., Richardson, J. A., Bassel-Duby, R., Olson, E. N.
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<strong>The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis.</strong>
|
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Dev. Cell 15: 261-271, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18694565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18694565</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18694565[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=18694565" 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.2008.07.002" target="_blank">Full Text</a>]
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</p>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 03/06/2019
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 2/20/2013<br>Cassandra L. Kniffin - updated : 10/24/2011<br>Cassandra L. Kniffin - updated : 8/16/2011<br>Ada Hamosh - updated : 8/25/2010<br>Cassandra L. Kniffin - updated : 9/1/2009<br>Patricia A. Hartz - updated : 7/30/2009<br>Cassandra L. Kniffin - updated : 9/14/2007<br>Paul J. Converse - updated : 4/3/2006
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz : 3/31/2005
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 03/07/2019
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 03/06/2019<br>carol : 09/24/2013<br>carol : 2/20/2013<br>ckniffin : 2/20/2013<br>carol : 10/25/2011<br>terry : 10/25/2011<br>ckniffin : 10/24/2011<br>ckniffin : 10/24/2011<br>alopez : 8/19/2011<br>alopez : 8/19/2011<br>ckniffin : 8/16/2011<br>mgross : 8/25/2010<br>wwang : 9/11/2009<br>ckniffin : 9/1/2009<br>mgross : 8/4/2009<br>terry : 7/30/2009<br>carol : 6/23/2009<br>carol : 11/30/2007<br>alopez : 9/24/2007<br>ckniffin : 9/14/2007<br>mgross : 4/6/2006<br>mgross : 4/6/2006<br>terry : 4/3/2006<br>mgross : 4/1/2005<br>mgross : 4/1/2005
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 609291
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</span>
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</h3>
|
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
|
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|
|
SPROUTY-RELATED EVH1 DOMAIN-CONTAINING PROTEIN 1; SPRED1
|
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SPRED1</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 703541007;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
|
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<em>
|
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Cytogenetic location: 15q14
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Genomic coordinates <span class="small">(GRCh38)</span> : 15:38,252,836-38,357,249 </span>
|
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</em>
|
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</strong>
|
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<span class="small">(from NCBI)</span>
|
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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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<h4>
|
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
|
|
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">
|
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<span class="mim-font">
|
|
15q14
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Legius syndrome
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
611431
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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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>Description</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>SPRED1 is a member of the Sprouty (see SPRY1; 602465)/SPRED family of proteins that regulate growth factor-induced activation of the MAP kinase cascade (see MAPK1, 176948) (Nonami et al., 2004). </p>
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</span>
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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>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Wakioka et al. (2001) cloned mouse Spred1 from an osteoclast cDNA library. The deduced 444-amino acid protein contains an N-terminal Enabled (ENA; 609061)/VASP (601703) homology-1 (EVH1) domain, a central KIT (164920)-binding domain (KBD), and a C-terminal SPRY domain. </p><p>Using Northern blot analysis, Kato et al. (2003) detected Spred1 expression in mouse brain, kidney, and colon, but not in any other tissues examined. Nonami et al. (2004) found Spred1 highly expressed in interleukin-3 (IL3; 147740)-dependent mouse hematopoietic cell lines and bone marrow-derived mast cells. </p><p>The SPRED1 protein has a molecular mass of 50 kD and contains 444 amino acids (review by Brems et al., 2012). </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Brems et al. (2007) noted that the SPRED1 gene contains 8 exons. </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>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>By genomic sequence analysis, Kato et al. (2003) mapped the SPRED1 gene to chromosome 15q13.2. They mapped the mouse Spred1 gene to chromosome 2E5 using FISH. </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>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Wakioka et al. (2001) found that mammalian Spred1 was phosphorylated in response to several growth factors, and efficient phosphorylation required the KBD domain. Overexpression of Spred1 inhibited NGF (162030)-induced neurite differentiation in rat PC12 cells, and both the EVH1 and SPRY domains were essential for the suppression. Wakioka et al. (2001) presented evidence that Spred1 and Spred2 (609292) could regulate differentiation in rat neuronal cells and mouse myocytes by inhibiting activation of MAP kinase. Inhibition appeared to occur through the formation of a Spred-Ras (190020) complex that inhibited activation of MAP kinase by suppressing phosphorylation and activation of Raf (see RAF1; 164760). </p><p>Kato et al. (2003) found that mouse Spred1 coprecipitated with and was phosphorylated by a constitutively activated Kit mutant. The KBD was required for Kit binding, but suppression of growth factor-induced MAP kinase required the SPRY domain. </p><p>Nonami et al. (2004) found that mouse Spred1 negatively regulated hematopoiesis by suppressing stem cell factor (KITLG; 184745)- and IL3-induced ERK (see MAPK3; 601795) activation. </p><p>MicroRNAs, such as MIR126 (611767), downregulate mRNA expression by binding to short complementary sequences in the 3-prime UTRs of target mRNAs. Wang et al. (2008) found that knockout of Mir126 in mice caused severe defects in vascularization. Using microarray analysis, they showed that endothelial cells from Mir126 -/- kidneys had elevated levels of Spred1, as well as numerous other genes involved in angiogenesis, cell adhesion, inflammatory/cytokine signaling, and cell cycle control. Real-time PCR and Western blot analysis confirmed upregulation of Spred1 in Mir126 -/- endothelial cells. Wang et al. (2008) identified a sequence complementary to the seed sequence of Mir126 in the 3-prime UTR of Spred1 mRNA, and they confirmed that Mir126 downregulated expression of a reporter gene that included the Spred1 3-prime UTR. Further experiments revealed that Mir126 augmented angiogenesis by diminishing the inhibitory influence of Spred1 on the MAP kinase pathway. </p><p>Hollander et al. (2010) found that miR212 (613487) was upregulated in the dorsal striatum of rats with a history of extended access to cocaine. Striatal miR212 decreased responsiveness to the motivational properties of cocaine by markedly amplifying the stimulatory effects of the drug on Creb (123810) signaling. Studies in rats and HEK cells showed that amplification of CREB signaling occurred through miR212-enhanced RAF1 activity, resulting in adenylyl cyclase sensitization and increased expression of the essential Creb coactivator TORC (see CRTC1; 607536). miR212 activated RAF1, at least in part, through repression of SPRED1. Hollander et al. (2010) concluded that striatal miR212 signaling has a key role in determining vulnerability to cocaine addiction. </p><p>To identify driver genes in mucosal melanoma, Ablain et al. (2018) sequenced hundreds of cancer-related genes in 43 human mucosal melanomas (see 155600), cataloging point mutations, amplifications, and deletions. The SPRED1 gene, which encodes a negative regulator of mitogen-activated protein kinase (MAPK) signaling, was inactivated in 37% of the tumors. Four distinct genotypes were associated with SPRED1 loss. Using a rapid, tissue-specific CRISPR technique to model these genotypes in zebrafish, Ablain et al. (2018) found that SPRED1 functions as a tumor suppressor, particularly in the context of KIT (164920) mutations. SPRED1 knockdown caused MAPK activation, increased cell proliferation, and conferred resistance to drugs inhibiting KIT tyrosine kinase activity. </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>In a review of the molecular genetics of Legius syndrome (LGSS; 611431), Brems et al. (2012) noted that SPRED1 mutations result in a loss of protein function and an inability of SPRED1 to downregulate the RAS-MAPK pathway. There are no apparent genotype/phenotype correlations. </p><p>In affected members of 5 unrelated families with Legius syndrome, Brems et al. (2007) identified 4 different heterozygous mutations in the SPRED1 gene (609291.0001-609291.0004). Screening of 86 additional patients who had undergone NF1 (162200) testing with negative results identified 7 additional SPRED1 mutations (see, e.g., 609291.0005). Melanocyte culture studies demonstrated that SPRED1 -/- cells had higher MAPK and ERK phosphorylation compared to heterozygous or wildtype cells. Further studies indicated that the mutations resulted in loss of function and that mutant SPRED1 proteins had lost their ability to inhibit RAF-MEK (see 176872)-ERK signaling. Haploinsufficiency appeared to be the mechanism. </p><p>Pasmant et al. (2009) identified 5 truncating mutations in the SPRED1 gene (see, e.g., 609291.0005 and 609291.0006) in affected members of 5 unrelated French families with Legius syndrome. The phenotype included a high prevalence of cafe-au-lait spots and axillary and groin freckling. Other variable features included lipomas and learning disabilities. Facial dysmorphism was not observed. As none of the patients had neurofibromas or Lisch nodules, Pasmant et al. (2009) suggested that the condition be named 'Legius syndrome.' </p><p>Spurlock et al. (2009) identified 6 different SPRED1 mutations (see, e.g., 609291.0007 and 609291.0008) in 6 of 85 probands with a mild NF1 phenotype and no neurofibromas. </p><p>Laycock-van Spyk et al. (2011) identified 6 different heterozygous nonsense or frameshift mutations in the SPRED1 gene in 6 of 115 patients with an NF1-like syndrome but without mutations in the NF1 gene. Combining their data with those from their earlier study (Spurlock et al., 2009), Laycock-van Spyk et al. (2011) estimated that SPRED1 mutations are found in about 6% of such patients. </p><p>Spencer et al. (2011) used multiplex ligation-dependent probe amplification (MLPA) to screen 510 NF1-negative patients with multiple cafe-au-lait spots with or without freckling and no other signs of NF1 for deletions in the SPRED1 gene. Four different deletions were detected, including 2 that segregated with the phenotype in 2 families and 2 that were apparently sporadic. All the deletions had different breakpoints, with 1 including 2 neighboring genes. Point mutations or 1- to 4-bp insertion/deletion mutations were found in 36 of the 510 individuals. Thus, deletions accounted for about 10% of the 40 detected SPRED1 mutations in this cohort, suggesting that dosage analysis of this gene should be performed in candidate patients. </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>Inoue et al. (2005) generated healthy and fertile Spred1-deficient mice by targeting exons encoding the KIT-binding and Sprouty-related domains. Spred1-deficient mice showed exaggerated allergen-induced airway hyperresponsiveness, eosinophilia, and mucus production in an allergic asthma model. They also had increased responsiveness, in terms of ERK signaling, to Il5 (147850) with subsequent overexpression of Il13 (147683) in eosinophils. Inoue et al. (2005) proposed that SPRED1 downregulation in the airway has a role in prolonged airway eosinophilia and asthma phenotypes. </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">
|
|
<strong>ALLELIC VARIANTS</strong>
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</span>
|
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<strong>9 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">
|
|
<strong>.0001 LEGIUS SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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|
SPRED1, ARG117TER
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<br />
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SNP: rs121434312,
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gnomAD: rs121434312,
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|
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ClinVar: RCV000001882, RCV001813180, RCV002225255, RCV002273919, RCV002336072
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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>In affected members of 2 unrelated families with autosomal dominant Legius syndrome (LGSS; 611431), Brems et al. (2007) identified a heterozygous 349C-T transition in exon 4 of the SPRED1 gene, resulting in an arg117-to-ter (R117X) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0002 LEGIUS SYNDROME</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SPRED1, ARG24TER
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<br />
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SNP: rs121434313,
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gnomAD: rs121434313,
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ClinVar: RCV000001883, RCV001172084
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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>In affected members of a family with Legius syndrome (LGSS; 611431), Brems et al. (2007) identified a heterozygous 70C-T transition in exon 3 of the SPRED1 gene, resulting in an arg24-to-ter (R24X) substitution. The R24X mutation was present in normal skin and melanocytes from a cafe-au-lait spot of 1 patient, but melanocytes from the cafe-au-lait spot showed an additional somatic SPRED1 mutation. The 2 mutations were located on different alleles, suggesting that SPRED1 function was completely absent in these cells. </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">
|
|
<strong>.0003 LEGIUS SYNDROME</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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SPRED1, IVS5DS, G-A, +1
|
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<br />
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|
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SNP: rs1566868058,
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ClinVar: RCV000001884
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with Legius syndrome (LGSS; 611431), Brems et al. (2007) identified a heterozygous G-to-A transition in the donor splice site of intron 5 (423+1G-A), resulting in the skipping of exon 5 and an out-of-frame deletion of 47 nucleotides at the mRNA level. </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">
|
|
<strong>.0004 LEGIUS SYNDROME</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SPRED1, GLN215TER
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<br />
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SNP: rs121434314,
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ClinVar: RCV000001885
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with Legius syndrome (LGSS; 611431), Brems et al. (2007) identified a heterozygous 643C-T transition in exon 7 of the SPRED1 gene, resulting in a gln215-to-ter (Q215X) substitution. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
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|
</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 LEGIUS SYNDROME</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SPRED1, ARG64TER
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|
<br />
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|
|
SNP: rs121434315,
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|
|
|
|
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ClinVar: RCV000001886, RCV003320544
|
|
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|
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an individual with Legius syndrome (LGSS; 611431), Brems et al. (2007) identified a heterozygous 190C-T transition in exon 3 of the SPRED1 gene, resulting in an arg64-to-ter (R64X) substitution. The patient had multiple cafe-au-lait spots and did not have a NF1 mutation. </p><p>In affected members of a French family with Legius syndrome, Pasmant et al. (2009) identified the same R64X mutation. The phenotype included a high prevalence of cafe-au-lait spots and axillary and groin freckling. Two patients had a lipoma and another had learning disability. None had neurofibromas or Lisch nodules. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 LEGIUS SYNDROME</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
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SPRED1, GLN213TER
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<br />
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|
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SNP: rs121434316,
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ClinVar: RCV000001887
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a French family with Legius syndrome (LGSS; 611431), Pasmant et al. (2009) identified a heterozygous 637C-T transition in exon 7 of the SPRED1 gene, resulting in a gln213-to-ter (Q213X) substitution. The phenotype included a high prevalence of cafe-au-lait spots and axillary and groin freckling. One patient had a learning disability. None had neurofibromas or Lisch nodules. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 LEGIUS SYNDROME</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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SPRED1, ARG262TER
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<br />
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|
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SNP: rs121434317,
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|
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ClinVar: RCV000001888
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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>In a father and son with Legius syndrome (LGSS; 611431), Spurlock et al. (2009) identified a heterozygous 784A-T transversion in exon 8 of the SPRED1 gene, resulting in an arg262-to-ter (R262X) substitution. Both had cafe-au-lait spots and axillary freckling, but no neurofibromas. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0008 LEGIUS SYNDROME</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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SPRED1, VAL44ASP
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<br />
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SNP: rs121434318,
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ClinVar: RCV000001889
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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>In 4 affected members of a 3-generation family with Legius syndrome (LGSS; 611431), Spurlock et al. (2009) identified a heterozygous 131T-A transversion in exon 3 of the SPRED1 gene, resulting in a val44-to-asp (V55D) substitution in a highly conserved residue. All had cafe-au-lait spots, but no neurofibromas. The father had a head circumference in the 90th percentile, but all other family members had a normal head size. </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>.0009 LEGIUS SYNDROME</strong>
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</h4>
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<span class="mim-text-font">
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SPRED1, 2-BP DEL, 1045AG
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<br />
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SNP: rs1566876941,
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ClinVar: RCV000023764, RCV002399334
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<p>In a mother and her 4 children, all with Legius syndrome (LGSS; 611431), Laycock-van Spyk et al. (2011) identified a heterozygous 2-bp deletion (1045delAG) in exon 7 of the SPRED1 gene, resulting in a frameshift and premature termination. The mother had perioral and ocular hyperpigmentation, hypertelorism, mild ptosis, and hypotonia. All patients had decreased IQ or learning difficulties. None had Lisch nodules or neurofibromas. </p>
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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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<ol>
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<li>
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<p class="mim-text-font">
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Ablain, J., Xu, M., Rothschild, H., Jordan, R. C., Mito, J. K., Daniels, B. H., Bell, C. F., Joseph, N. M., Wu, H., Bastian, B. C., Zon, L. I., Yeh, I.
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<strong>Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma.</strong>
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Science 362: 1055-1060, 2018.
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[PubMed: 30385465]
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[Full Text: https://doi.org/10.1126/science.aau6509]
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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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Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K. Kato, R., Somers, R., Messiaen, L., De Schepper, S., Fryns, J.-P., Cools, J., Marynen, P., Thomas, G., Yoshimura, A., Legius, E.
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<strong>Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. (Letter)</strong>
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Nature Genet. 39: 1120-1126, 2007.
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[PubMed: 17704776]
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[Full Text: https://doi.org/10.1038/ng2113]
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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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Brems, H., Pasmant, E., Van Minkelen, R., Wimmer, K., Upadhyaya, M., Legius, E., Messiaen, L.
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<strong>Review and update of SPRED1 mutations causing Legius syndrome.</strong>
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Hum. Mutat. 33: 1538-1546, 2012.
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[PubMed: 22753041]
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[Full Text: https://doi.org/10.1002/humu.22152]
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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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Hollander, J. A., Im, H.-I., Amelio, A. L., Kocerha, J., Bali, P., Lu, Q., Willoughby, D., Wahlestedt, C., Conkright, M. D., Kenny, P. J.
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<strong>Striatal microRNA controls cocaine intake through CREB signalling.</strong>
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Nature 466: 197-202, 2010.
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[PubMed: 20613834]
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[Full Text: https://doi.org/10.1038/nature09202]
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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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Inoue, H., Kato, R., Fukuyama, S., Nonami, A., Taniguchi, K., Matsumoto, K., Nakano, T., Tsuda, M., Matsumura, M., Kubo, M., Ishikawa, F., Moon, B., Takatsu, K., Nakanishi, Y., Yoshimura, A.
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<strong>Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness.</strong>
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J. Exp. Med. 201: 73-82, 2005.
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[PubMed: 15630138]
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[Full Text: https://doi.org/10.1084/jem.20040616]
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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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Kato, R., Nonami, A., Taketomi, T., Wakioka, T., Kuroiwa, A., Matsuda, Y., Yoshimura, A.
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<strong>Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation.</strong>
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Biochem. Biophys. Res. Commun. 302: 767-772, 2003.
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[PubMed: 12646235]
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[Full Text: https://doi.org/10.1016/s0006-291x(03)00259-6]
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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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Laycock-van Spyk, S., Jim, H. P., Thomas, L., Spurlock, G., Fares, L., Palmer-Smith, S., Kini, U., Saggar, A., Patton, M., Mautner, V., Pilz, D. T., Upadhyaya, M.
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<strong>Identification of five novel SPRED1 germline mutations in Legius syndrome. (Letter)</strong>
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Clin. Genet. 80: 93-96, 2011.
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[PubMed: 21649642]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2010.01618.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Nonami, A., Kato, R., Taniguchi, K., Yoshiga, D., Taketomi, T., Fukuyama, S., Harada, M., Sasaki, A., Yoshimura, A.
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<strong>Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells.</strong>
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J. Biol. Chem. 279: 52543-52551, 2004.
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[PubMed: 15465815]
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[Full Text: https://doi.org/10.1074/jbc.M405189200]
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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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Pasmant, E., Sabbagh, A., Hanna, N., Masliah-Planchon, J., Jolly, E., Goussard, P., Ballerini, P., Cartault, F., Barbarot, S., Landman-Parker, J., Soufir, N., Parfait, B., Vidaud, M., Wolkenstein, P., Vidaud, D., France, R. N. F.
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<strong>SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype.</strong>
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J. Med. Genet. 46: 425-430, 2009.
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[PubMed: 19366998]
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[Full Text: https://doi.org/10.1136/jmg.2008.065243]
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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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Spencer, E., Davis, J., Mikhail, F., Fu, C., Vijzelaar, R., Zackai, E. H., Feret, H., Meyn, M. S., Shugar, A., Bellus, G., Kocsis, K., Kivirikko, S., Poyhonen, M., Messiaen, L.
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<strong>Identification of SPRED1 deletions using RT-PCR, multiplex ligation-dependent probe amplification and quantitative PCR.</strong>
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Am. J. Med. Genet. 155A: 1352-1359, 2011.
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[PubMed: 21548021]
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[Full Text: https://doi.org/10.1002/ajmg.a.33894]
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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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Spurlock, G., Bennett, E., Chuzhanova, N., Thomas, N., Jim, H.-P., Side, L., Davies, S., Haan, E., Kerr, B., Huson, S. M., Upadhyaya, M.
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|
<strong>SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype.</strong>
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J. Med. Genet. 46: 431-437, 2009.
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[PubMed: 19443465]
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[Full Text: https://doi.org/10.1136/jmg.2008.065474]
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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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Wakioka, T., Sasaki, A., Kato, R., Shouda, T., Matsumoto, A., Miyoshi, K., Tsuneoka, M., Komiya, S., Baron, R., Yoshimura, A.
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<strong>Spred is a Sprouty-related suppressor of Ras signalling.</strong>
|
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Nature 412: 647-651, 2001.
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[PubMed: 11493923]
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[Full Text: https://doi.org/10.1038/35088082]
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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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Wang, S., Aurora, A. B., Johnson, B. A., Qi, X., McAnally, J., Hill, J. A., Richardson, J. A., Bassel-Duby, R., Olson, E. N.
|
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<strong>The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis.</strong>
|
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Dev. Cell 15: 261-271, 2008.
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[PubMed: 18694565]
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[Full Text: https://doi.org/10.1016/j.devcel.2008.07.002]
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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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Contributors:
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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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Ada Hamosh - updated : 03/06/2019<br>Cassandra L. Kniffin - updated : 2/20/2013<br>Cassandra L. Kniffin - updated : 10/24/2011<br>Cassandra L. Kniffin - updated : 8/16/2011<br>Ada Hamosh - updated : 8/25/2010<br>Cassandra L. Kniffin - updated : 9/1/2009<br>Patricia A. Hartz - updated : 7/30/2009<br>Cassandra L. Kniffin - updated : 9/14/2007<br>Paul J. Converse - updated : 4/3/2006
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carol : 03/07/2019<br>alopez : 03/06/2019<br>carol : 09/24/2013<br>carol : 2/20/2013<br>ckniffin : 2/20/2013<br>carol : 10/25/2011<br>terry : 10/25/2011<br>ckniffin : 10/24/2011<br>ckniffin : 10/24/2011<br>alopez : 8/19/2011<br>alopez : 8/19/2011<br>ckniffin : 8/16/2011<br>mgross : 8/25/2010<br>wwang : 9/11/2009<br>ckniffin : 9/1/2009<br>mgross : 8/4/2009<br>terry : 7/30/2009<br>carol : 6/23/2009<br>carol : 11/30/2007<br>alopez : 9/24/2007<br>ckniffin : 9/14/2007<br>mgross : 4/6/2006<br>mgross : 4/6/2006<br>terry : 4/3/2006<br>mgross : 4/1/2005<br>mgross : 4/1/2005
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