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Entry
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- *604579 - FRIZZLED CLASS RECEPTOR 4; FZD4
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- OMIM
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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Advanced Search
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<a href="/search/advanced/entry"> OMIM </a>
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*604579</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604579">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000174804;t=ENST00000531380" 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=8322" 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=604579" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000174804;t=ENST00000531380" 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_012193" 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_012193" 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=604579" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=05203&isoform_id=05203_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/FZD4" 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/6277266,13548681,20152290,22547161,38565059,62298045,109731485,109731914,119595553,158258973" 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/Q9ULV1" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=8322" 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=ENSG00000174804;t=ENST00000531380" 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=FZD4" 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=FZD4" 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+8322" 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/FZD4" 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:8322" 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/8322" 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=chr11&hgg_gene=ENST00000531380.2&hgg_start=86945679&hgg_end=86955395&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:4042" 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:4042" 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/fzd4" 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=604579[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=604579[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000174804" 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=FZD4" 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=FZD4" 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=FZD4" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=FZD4&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/PA28459" 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:4042" 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/FBgn0027342.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:108520" 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/FZD4#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:108520" 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/8322/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=8322" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00003238;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-990415-217" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:8322" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=FZD4&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> 415297005<br />
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<strong>ICD10CM:</strong> H35.1, H35.10, H35.17<br />
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<strong>ICD9CM:</strong> 362.20, 362.21<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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604579
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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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FRIZZLED CLASS RECEPTOR 4; FZD4
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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FRIZZLED, DROSOPHILA, HOMOLOG OF, 4
|
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</span>
|
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=FZD4" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FZD4</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/11/811?start=-3&limit=10&highlight=811">11q14.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:86945679-86955395&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'})">11:86,945,679-86,955,395</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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Exudative vitreoretinopathy 1
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/604579" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/604579" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>Members of the 'frizzled' (FZ) gene family (see <a href="/entry/606143">606143</a>) encode 7-transmembrane domain proteins that are receptors for Wnt (see Wnt5A; <a href="/entry/164975">164975</a>) signaling proteins.</p>
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<p>By screening a human fetal lung cDNA library with an FZD4 cDNA fragment isolated from a human gastric cancer cDNA pool, <a href="#3" class="mim-tip-reference" title="Kirikoshi, H., Sagara, N., Koike, J., Tanaka, K., Sekihara, H., Hirai, M., Katoh, M. <strong>Molecular cloning and characterization of human frizzled-4 on chromosome 11q14-q21.</strong> Biochem. Biophys. Res. Commun. 264: 955-961, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10544037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10544037</a>] [<a href="https://doi.org/10.1006/bbrc.1999.1612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10544037">Kirikoshi et al. (1999)</a> obtained a full-length cDNA of FZD4. FZD4 encodes a deduced 537-amino acid protein that has a cysteine-rich domain (CRD) in the N-terminal extracellular region, 2 cysteine residues in the second and third extracellular loops, 2 extracellular N-linked glycosylation sites, and the S/T-X-V motif in the C terminus. Amino acid sequence identity with other FZD proteins ranged from 39 to 52% in the N terminus to 42 to 69% in the transmembrane domains. Northern blot analysis revealed expression of a 7.7-kb transcript in large amounts in adult heart, skeletal muscle, ovary, and fetal kidney, in moderate amounts in adult liver, kidney, pancreas, spleen, and fetal lung, and in small amounts in placenta, adult lung, prostate, testis, colon, fetal brain, and liver. Expression was also strong in HeLa cells but not in several cancer cell lines. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10544037" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By screening a fetal lung cDNA library using the C terminus of FZD4 as probe, followed by PCR of a fetal kidney cDNA library, <a href="#9" class="mim-tip-reference" title="Sagara, N., Kirikoshi, H., Terasaki, H., Yasuhiko, Y., Toda, G., Shiokawa, K., Katoh, M. <strong>FZD4S, a splicing variant of frizzled-4, encodes a soluble-type positive regulator of the WNT signaling pathway.</strong> Biochem. Biophys. Res. Commun. 282: 750-756, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11401527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11401527</a>] [<a href="https://doi.org/10.1006/bbrc.2001.4634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11401527">Sagara et al. (2001)</a> cloned an FZD4 variant, which they called FZD4S. FZD4S is unspliced and includes exon 1, intron 1, and exon 2. The deduced protein contains only 125 amino acids due to the introduction of a stop codon within the retained intron. The N-terminal 98 amino acids of FZD4S are identical to those of the full-length FZD4 protein, but the last 27 residues are unique. Compared with FZD4, FZD4S retains the N-terminal signal peptide and the N-terminal part of the CRD, but not the latter half of the CRD or the 7 transmembrane domains, indicating that FZD4S is likely to be a soluble protein. Northern blot analysis detected modest expression of a 10.0-kb mRNA in fetal kidney and faint expression in adult heart and fetal lung. RNA dot blot analysis detected expression in adult heart and lung and in fetal kidney and lung. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11401527" 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="#9" class="mim-tip-reference" title="Sagara, N., Kirikoshi, H., Terasaki, H., Yasuhiko, Y., Toda, G., Shiokawa, K., Katoh, M. <strong>FZD4S, a splicing variant of frizzled-4, encodes a soluble-type positive regulator of the WNT signaling pathway.</strong> Biochem. Biophys. Res. Commun. 282: 750-756, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11401527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11401527</a>] [<a href="https://doi.org/10.1006/bbrc.2001.4634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11401527">Sagara et al. (2001)</a> injected synthetic FZD4S mRNA into the ventral marginal zone of Xenopus embryos at the 4-cell stage. The injected FZD4S did not induce axis duplication by itself, but augmented the axis duplication potential of coinjected Xenopus Wnt8 (see <a href="/entry/601396">601396</a>) mRNA. <a href="#9" class="mim-tip-reference" title="Sagara, N., Kirikoshi, H., Terasaki, H., Yasuhiko, Y., Toda, G., Shiokawa, K., Katoh, M. <strong>FZD4S, a splicing variant of frizzled-4, encodes a soluble-type positive regulator of the WNT signaling pathway.</strong> Biochem. Biophys. Res. Commun. 282: 750-756, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11401527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11401527</a>] [<a href="https://doi.org/10.1006/bbrc.2001.4634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11401527">Sagara et al. (2001)</a> concluded that the FZD4S variant of FZD4 is a soluble protein that can activate the WNT signaling pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11401527" 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 findings of <a href="#8" class="mim-tip-reference" title="Robitaille, J., MacDonald, M. L. E., Kaykas, A., Sheldahl, L. C., Zeisler, J., Dube, M.-P., Zhang, L.-H., Singaraja, R. R., Guernsey, D. L., Zhang, B., Siebert, L. F., Hoskin-Mott, A., Trese, M. T., Pimstone, S. N., Shastry, B. S., Moon, R. T., Hayden, M. R., Goldberg, Y. P., Samuels, M. E. <strong>Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.</strong> Nature Genet. 32: 326-330, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12172548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12172548</a>] [<a href="https://doi.org/10.1038/ng957" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12172548">Robitaille et al. (2002)</a> supported a function for FZD4 in retinal angiogenesis. <a href="#8" class="mim-tip-reference" title="Robitaille, J., MacDonald, M. L. E., Kaykas, A., Sheldahl, L. C., Zeisler, J., Dube, M.-P., Zhang, L.-H., Singaraja, R. R., Guernsey, D. L., Zhang, B., Siebert, L. F., Hoskin-Mott, A., Trese, M. T., Pimstone, S. N., Shastry, B. S., Moon, R. T., Hayden, M. R., Goldberg, Y. P., Samuels, M. E. <strong>Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.</strong> Nature Genet. 32: 326-330, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12172548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12172548</a>] [<a href="https://doi.org/10.1038/ng957" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12172548">Robitaille et al. (2002)</a> injected Xenopus laevis embryos with wildtype and familial exudative vitreoretinopathy (FEVR; <a href="/entry/133780">133780</a>)-associated FZD4 mutants. They found that wildtype FZD4, but not mutant FZD4, activated CAMK2 (see <a href="/entry/114078">114078</a>) and PKC (see <a href="/entry/176960">176960</a>), components of the Wnt/Ca(2+) signaling pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12172548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Chen, W., ten Berge, D., Brown, J., Ahn, S., Hu, L. A., Miller, W. E., Caron, M. G., Barak, L. S., Nusse, R., Lefkowitz, R. J. <strong>Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of frizzled 4.</strong> Science 301: 1391-1394, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12958364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12958364</a>] [<a href="https://doi.org/10.1126/science.1082808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12958364">Chen et al. (2003)</a> found that endocytosis of FZD4 in human embryonic kidney cells was dependent on added WNT5A protein and was accomplished by the multifunctional adaptor protein beta-arrestin-2 (<a href="/entry/107941">107941</a>), which was recruited to FZD4 by binding to phosphorylated dishevelled-2 (DVL2; <a href="/entry/602151">602151</a>). The authors concluded that their findings provided a previously unrecognized mechanism for receptor recruitment of beta-arrestin and demonstrated that dishevelled plays an important role in the endocytosis of frizzled, as well as in promoting signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12958364" 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 a complementation assay, <a href="#2" class="mim-tip-reference" title="Kaykas, A., Yang-Snyder, J., Heroux, M., Shah, K. V., Bouvier, M., Moon, R. T. <strong>Mutant frizzled 4 associated with vitreoretinopathy traps wild-type frizzled in the endoplasmic reticulum by oligomerization.</strong> Nature Cell Biol. 6: 52-58, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14688793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14688793</a>] [<a href="https://doi.org/10.1038/ncb1081" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14688793">Kaykas et al. (2004)</a> found that FZD4 could form homodimers. It could also form heterodimers with other FZD proteins, including rat Fzd1 (<a href="/entry/603408">603408</a>), rat Fzd2 (<a href="/entry/600667">600667</a>), Xenopus Fzd7 (<a href="/entry/603410">603410</a>), and human FZD9 (<a href="/entry/601766">601766</a>). Strongest affinity was displayed by proteins with similar amino acid sequence. <a href="#2" class="mim-tip-reference" title="Kaykas, A., Yang-Snyder, J., Heroux, M., Shah, K. V., Bouvier, M., Moon, R. T. <strong>Mutant frizzled 4 associated with vitreoretinopathy traps wild-type frizzled in the endoplasmic reticulum by oligomerization.</strong> Nature Cell Biol. 6: 52-58, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14688793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14688793</a>] [<a href="https://doi.org/10.1038/ncb1081" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14688793">Kaykas et al. (2004)</a> found that an FEVR-associated FZD4 mutant with a frameshift at leu501 (<a href="#0002">604579.0002</a>), which does not accumulate at the plasma membrane, was trapped in the endoplasmic reticulum. Through heterodimerization, this mutant FZD4 could trap wildtype FZD4 and inhibit its signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14688793" 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>Incomplete retinal vascularization occurs in both Norrie disease (<a href="/entry/310600">310600</a>) and FEVR. Norrin, the protein product of the NDP gene (<a href="/entry/300658">300658</a>), is a secreted protein. One form of FEVR is caused by defects in FZD4, a presumptive Wnt receptor. <a href="#10" class="mim-tip-reference" title="Xu, Q., Wang, Y., Dabdoub, A., Smallwood, P. M., Williams, J., Woods, C., Kelley, M. W., Jiang, L., Tasman, W., Zhang, K., Nathans, J. <strong>Vascular development in the retina and inner ear: control by norrin and frizzled-4, a high-affinity ligand-receptor pair.</strong> Cell 116: 883-895, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15035989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15035989</a>] [<a href="https://doi.org/10.1016/s0092-8674(04)00216-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15035989">Xu et al. (2004)</a> determined that norrin and FZD4 function as a ligand-receptor pair based on the similarity in vascular phenotypes caused by norrin and FZD4 mutations in humans and mice; the specificity and high affinity of norrin-FZD4 binding; the high efficiency with which norrin induces FZD4- and LRP (see <a href="/entry/107770">107770</a>)-dependent activation of the classical Wnt pathway; and the signaling defects displayed by disease-associated variants of norrin and FZD4. These data defined a norrin-FZD4 signaling system that plays a central role in vascular development in the eye and ear, and they indicated that ligands unrelated to Wnts can act through frizzled receptors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15035989" 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 yeast 2-hybrid assays, <a href="#12" class="mim-tip-reference" title="Yao, R., Natsume, Y., Noda, T. <strong>MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap.</strong> Oncogene 23: 6023-6030, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15195140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15195140</a>] [<a href="https://doi.org/10.1038/sj.onc.1207817" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15195140">Yao et al. (2004)</a> found that PDZ domain 1 of mouse Magi3 (<a href="/entry/615943">615943</a>) interacted with the C-terminal PDZ-binding motifs of Fzd4 and Fzd7. PDZ domain 1 also interacted with Ltap (VANGL2; <a href="/entry/600533">600533</a>), another planar cell polarity signaling protein. Magi3, Fzd4, and Ltap independently localized to sites of cell-cell contacts in epithelial cells, and these 3 proteins interacted in a complex that required Magi3. Magi3 strongly enhanced Rac (see <a href="/entry/602048">602048</a>)-dependent Jnk (see <a href="/entry/601158">601158</a>) activation by Fzd4 and Ltap. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15195140" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#11" class="mim-tip-reference" title="Yang, S., Wu, Y., Xu, T.-H., de Waal, P. W., He, Y., Pu, M., Chen, Y., DeBruine, Z. J., Zhang, B., Zaidi, S. A., Popov, P., Guo, Y., and 13 others. <strong>Crystal structure of the Frizzled 4 receptor in a ligand-free state.</strong> Nature 560: 666-670, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30135577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30135577</a>] [<a href="https://doi.org/10.1038/s41586-018-0447-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30135577">Yang et al. (2018)</a> presented the atomic-resolution structure of the human FZD4 transmembrane domain in the absence of a bound ligand. The structure revealed an unusual transmembrane architecture in which helix VI is short and tightly packed, and is distinct from all other GPCR structures reported so far. Within this unique transmembrane fold is an extremely narrow and highly hydrophilic pocket that is not amenable to the binding of traditional GPCR ligands. <a href="#11" class="mim-tip-reference" title="Yang, S., Wu, Y., Xu, T.-H., de Waal, P. W., He, Y., Pu, M., Chen, Y., DeBruine, Z. J., Zhang, B., Zaidi, S. A., Popov, P., Guo, Y., and 13 others. <strong>Crystal structure of the Frizzled 4 receptor in a ligand-free state.</strong> Nature 560: 666-670, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30135577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30135577</a>] [<a href="https://doi.org/10.1038/s41586-018-0447-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30135577">Yang et al. (2018)</a> showed that such a pocket is conserved across all FZDs, which may explain the long-standing difficulties in the development of ligands for these receptors. Molecular dynamics simulations on the microsecond timescale and mutational analysis uncovered 2 coupled, dynamic kinks located at helix VII that are involved in FZD4 activation. The stability of the structure in its ligand-free form, an unfavorable pocket for ligand binding, and the 2 unusual kinks on helix VII suggested that FZDs may have evolved a novel ligand recognition and activation mechanism that is distinct from that of other GPCRs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30135577" 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 FISH, <a href="#3" class="mim-tip-reference" title="Kirikoshi, H., Sagara, N., Koike, J., Tanaka, K., Sekihara, H., Hirai, M., Katoh, M. <strong>Molecular cloning and characterization of human frizzled-4 on chromosome 11q14-q21.</strong> Biochem. Biophys. Res. Commun. 264: 955-961, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10544037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10544037</a>] [<a href="https://doi.org/10.1006/bbrc.1999.1612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10544037">Kirikoshi et al. (1999)</a> mapped the FZD4 gene to chromosome 11q14-q21. By positional cloning, <a href="#8" class="mim-tip-reference" title="Robitaille, J., MacDonald, M. L. E., Kaykas, A., Sheldahl, L. C., Zeisler, J., Dube, M.-P., Zhang, L.-H., Singaraja, R. R., Guernsey, D. L., Zhang, B., Siebert, L. F., Hoskin-Mott, A., Trese, M. T., Pimstone, S. N., Shastry, B. S., Moon, R. T., Hayden, M. R., Goldberg, Y. P., Samuels, M. E. <strong>Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.</strong> Nature Genet. 32: 326-330, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12172548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12172548</a>] [<a href="https://doi.org/10.1038/ng957" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12172548">Robitaille et al. (2002)</a> mapped the FZD4 gene to chromosome 11q14.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12172548+10544037" 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 affected members of 2 unrelated families with autosomal dominant familial exudative vitreoretinopathy (EVR1; <a href="/entry/133780">133780</a>), <a href="#8" class="mim-tip-reference" title="Robitaille, J., MacDonald, M. L. E., Kaykas, A., Sheldahl, L. C., Zeisler, J., Dube, M.-P., Zhang, L.-H., Singaraja, R. R., Guernsey, D. L., Zhang, B., Siebert, L. F., Hoskin-Mott, A., Trese, M. T., Pimstone, S. N., Shastry, B. S., Moon, R. T., Hayden, M. R., Goldberg, Y. P., Samuels, M. E. <strong>Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.</strong> Nature Genet. 32: 326-330, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12172548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12172548</a>] [<a href="https://doi.org/10.1038/ng957" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12172548">Robitaille et al. (2002)</a> identified 2 different heterozygous deletions in exon 2 of the FZD4 gene (<a href="#0001">604579.0001</a>; <a href="#0002">604579.0002</a>). Both mutations altered the seventh transmembrane domain and the intracellular carboxy-terminal tail, respectively. No mutations in FZD4 were detected in 3 other small families with FEVR. <a href="#8" class="mim-tip-reference" title="Robitaille, J., MacDonald, M. L. E., Kaykas, A., Sheldahl, L. C., Zeisler, J., Dube, M.-P., Zhang, L.-H., Singaraja, R. R., Guernsey, D. L., Zhang, B., Siebert, L. F., Hoskin-Mott, A., Trese, M. T., Pimstone, S. N., Shastry, B. S., Moon, R. T., Hayden, M. R., Goldberg, Y. P., Samuels, M. E. <strong>Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.</strong> Nature Genet. 32: 326-330, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12172548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12172548</a>] [<a href="https://doi.org/10.1038/ng957" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12172548">Robitaille et al. (2002)</a> presented data indicating that the changes in FZD4 in these families with autosomal dominant FEVR represented loss-of-function mutations. Following transfection in COS-7 cells, wildtype FZD4 and the FEVR-related FZD4 mutant lacking met493 and trp494 accumulated at the plasma membrane; however, the mutant containing the frameshift at leu501 did not. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12172548" 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 an infant with advanced retinopathy of prematurity (see <a href="/entry/133780">133780</a>), <a href="#5" class="mim-tip-reference" title="MacDonald, M. L. E., Goldberg, Y. P., MacFarlane, J., Samuels, M. E., Trese, M. T., Shastry, B. S. <strong>Genetic variants of frizzled-4 gene in familial exudative vitreoretinopathy and advanced retinopathy of prematurity. (Letter)</strong> Clin. Genet. 67: 363-366, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15733276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15733276</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00408.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15733276">MacDonald et al. (2005)</a> identified heterozygosity for a missense mutation in the FZD4 gene (<a href="#0006">604579.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15733276" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using a norrin-based reporter assay to analyze the effects of FEVR-causing mutations, <a href="#7" class="mim-tip-reference" title="Qin, M., Kondo, H., Tahira, T., Hayashi, K. <strong>Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy.</strong> Hum. Genet. 122: 615-623, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17955262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17955262</a>] [<a href="https://doi.org/10.1007/s00439-007-0438-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17955262">Qin et al. (2008)</a> demonstrated that a nonsense mutation in FZD4 completely abolished signaling activity, whereas missense mutations in FZD4 and LRP5 (<a href="/entry/603506">603506</a>) caused a moderate level of reduction, and a double missense mutation in both genes caused a severe reduction in activity, correlating roughly with clinical phenotypes. Norrin mutants, however, showed variable effects on signal transduction, and no correlation with clinical phenotypes was observed; norrin mutants also showed impaired cell surface binding. <a href="#7" class="mim-tip-reference" title="Qin, M., Kondo, H., Tahira, T., Hayashi, K. <strong>Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy.</strong> Hum. Genet. 122: 615-623, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17955262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17955262</a>] [<a href="https://doi.org/10.1007/s00439-007-0438-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17955262">Qin et al. (2008)</a> concluded that norrin signaling is involved in FEVR pathogenesis, but suggested the presence of an unknown parallel pathway at the level of receptor/ligand binding as evidenced by the moderate and variable signal reduction lacking a clear genotype/phenotype correlation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17955262" 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">rs80358301 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358301;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=rs80358301" 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=rs80358301" 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=RCV000005818 OR RCV000478323" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005818, RCV000478323" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005818...</a>
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<p>In a large Canadian kindred of British descent with exudative vitreoretinopathy (EVR1; <a href="/entry/133780">133780</a>), <a href="#8" class="mim-tip-reference" title="Robitaille, J., MacDonald, M. L. E., Kaykas, A., Sheldahl, L. C., Zeisler, J., Dube, M.-P., Zhang, L.-H., Singaraja, R. R., Guernsey, D. L., Zhang, B., Siebert, L. F., Hoskin-Mott, A., Trese, M. T., Pimstone, S. N., Shastry, B. S., Moon, R. T., Hayden, M. R., Goldberg, Y. P., Samuels, M. E. <strong>Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.</strong> Nature Genet. 32: 326-330, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12172548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12172548</a>] [<a href="https://doi.org/10.1038/ng957" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12172548">Robitaille et al. (2002)</a> demonstrated that affected members had a mutation in the FZD4 gene: deletion of nucleotides 1479-1484, resulting in deletion of 2 highly conserved amino acids, met493 and trp494. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12172548" 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">rs80358303 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358303;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=rs80358303" 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=rs80358303" 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=RCV000005819 OR RCV001091739" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005819, RCV001091739" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005819...</a>
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<p>In a family of European descent with exudative vitreoretinopathy (EVR1; <a href="/entry/133780">133780</a>), <a href="#8" class="mim-tip-reference" title="Robitaille, J., MacDonald, M. L. E., Kaykas, A., Sheldahl, L. C., Zeisler, J., Dube, M.-P., Zhang, L.-H., Singaraja, R. R., Guernsey, D. L., Zhang, B., Siebert, L. F., Hoskin-Mott, A., Trese, M. T., Pimstone, S. N., Shastry, B. S., Moon, R. T., Hayden, M. R., Goldberg, Y. P., Samuels, M. E. <strong>Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.</strong> Nature Genet. 32: 326-330, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12172548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12172548</a>] [<a href="https://doi.org/10.1038/ng957" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12172548">Robitaille et al. (2002)</a> demonstrated that affected members carried a 2-bp deletion in the FZD4 gene, resulting in frameshift at leu501, creating a stop codon at residue 533. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12172548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 EXUDATIVE VITREORETINOPATHY 1</strong>
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EXUDATIVE VITREORETINOPATHY, DIGENIC, INCLUDED
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FZD4, ARG417GLN
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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> rs80358294 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358294;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/rs80358294?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=rs80358294" 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=rs80358294" 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=RCV000005820 OR RCV000005821" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005820, RCV000005821" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005820...</a>
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<p>In patients with exudative vitreoretinopathy (EVR1; <a href="/entry/133780">133780</a>), <a href="#4" class="mim-tip-reference" title="Kondo, H., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K. <strong>Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.</strong> Brit. J. Ophthal. 87: 1291-1295, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14507768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14507768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14507768[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/10.1136/bjo.87.10.1291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14507768">Kondo et al. (2003)</a> identified a heterozygous 1250G-A transition in exon 2 of the FZD4 gene, resulting in an arg417-to-gln (R417Q) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14507768" 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="Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H. <strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong> Hum. Mutat. 26: 104-112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>] [<a href="https://doi.org/10.1002/humu.20191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981244">Qin et al. (2005)</a> reported a Japanese family with digenic inheritance of EVR. Affected members had a heterozygous R417Q mutation in the FZD4 gene consistent with EVR1 and a heterozygous mutation in the LRP5 gene (R444C; <a href="/entry/603506#0026">603506.0026</a>) consistent with EVR4 (<a href="/entry/601813">601813</a>). The 2 mutations cosegregated in the family, indicating that both mutations were located on the same chromosome consistent with digenic inheritance. The ocular phenotype in this family tended to be more severe compared to that of the family reported by <a href="#4" class="mim-tip-reference" title="Kondo, H., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K. <strong>Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.</strong> Brit. J. Ophthal. 87: 1291-1295, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14507768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14507768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14507768[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/10.1136/bjo.87.10.1291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14507768">Kondo et al. (2003)</a> with the FZD4 R417Q mutation alone. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15981244+14507768" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 EXUDATIVE VITREORETINOPATHY 1</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"><span class="text-primary">●</span> rs80358293 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358293;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/rs80358293?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=rs80358293" 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=rs80358293" 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=RCV000005822 OR RCV003555930" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005822, RCV003555930" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005822...</a>
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<p>In a Japanese girl with exudative vitreoretinopathy (EVR1; <a href="/entry/133780">133780</a>), <a href="#13" class="mim-tip-reference" title="Yoshida, S., Arita, R.-I., Yoshida, A., Tada, H., Emori, A., Noda, Y., Nakao, S., Fujisawa, K., Ishibashi, T. <strong>Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative vitreoretinopathy.</strong> Am. J. Ophthal. 138: 670-671, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15488808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15488808</a>] [<a href="https://doi.org/10.1016/j.ajo.2004.05.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15488808">Yoshida et al. (2004)</a> identified a heterozygous 1026A-G transition in the FZD4 gene, resulting in a met342-to-val (M342V) substitution. She had esotropia and exudative retinal detachment at age 3 years. Her asymptomatic father, who also carried the mutation, was found to have bilateral avascular areas in the peripheral retina. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15488808" 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">rs80358292 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358292;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=rs80358292" 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=rs80358292" 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=RCV000005823" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005823" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005823</a>
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<p>In a Japanese infant with exudative vitreoretinopathy (EVR1; <a href="/entry/133780">133780</a>) and bilateral retinal folds, <a href="#6" class="mim-tip-reference" title="Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H. <strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong> Hum. Mutat. 26: 104-112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>] [<a href="https://doi.org/10.1002/humu.20191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981244">Qin et al. (2005)</a> identified a heterozygous 1005G-C transversion in exon 2 of the FZD4 gene, resulting in a trp335-to-cys (W335C) substitution. The child's asymptomatic mother, who also carried the mutation, exhibited bilateral peripheral retinal avascularization with vascular tortuosity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15981244" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 RETINOPATHY OF PREMATURITY</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"><span class="text-primary">●</span> rs104894223 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894223;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/rs104894223?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=rs104894223" 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=rs104894223" 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=RCV000005824 OR RCV001262378 OR RCV001493514 OR RCV004757098" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005824, RCV001262378, RCV001493514, RCV004757098" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005824...</a>
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<p>In an infant with advanced retinopathy of prematurity (see <a href="/entry/133780">133780</a>), <a href="#5" class="mim-tip-reference" title="MacDonald, M. L. E., Goldberg, Y. P., MacFarlane, J., Samuels, M. E., Trese, M. T., Shastry, B. S. <strong>Genetic variants of frizzled-4 gene in familial exudative vitreoretinopathy and advanced retinopathy of prematurity. (Letter)</strong> Clin. Genet. 67: 363-366, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15733276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15733276</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00408.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15733276">MacDonald et al. (2005)</a> identified heterozygosity for a 766A-G transition in the FZD4 gene, resulting in an ile256-to-val (I256V) substitution. The mutation was not observed in 200 normal chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15733276" 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="references"class="mim-anchor"></a>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<ol>
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<a id="1" class="mim-anchor"></a>
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<a id="Chen2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Chen, W., ten Berge, D., Brown, J., Ahn, S., Hu, L. A., Miller, W. E., Caron, M. G., Barak, L. S., Nusse, R., Lefkowitz, R. J.
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<strong>Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of frizzled 4.</strong>
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Science 301: 1391-1394, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12958364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12958364</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12958364" 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.1082808" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
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<a id="Kaykas2004" class="mim-anchor"></a>
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Kaykas, A., Yang-Snyder, J., Heroux, M., Shah, K. V., Bouvier, M., Moon, R. T.
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<strong>Mutant frizzled 4 associated with vitreoretinopathy traps wild-type frizzled in the endoplasmic reticulum by oligomerization.</strong>
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Nature Cell Biol. 6: 52-58, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14688793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14688793</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14688793" 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/ncb1081" target="_blank">Full Text</a>]
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</p>
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<a id="3" class="mim-anchor"></a>
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<a id="Kirikoshi1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kirikoshi, H., Sagara, N., Koike, J., Tanaka, K., Sekihara, H., Hirai, M., Katoh, M.
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<strong>Molecular cloning and characterization of human frizzled-4 on chromosome 11q14-q21.</strong>
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Biochem. Biophys. Res. Commun. 264: 955-961, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10544037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10544037</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10544037" 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/10.1006/bbrc.1999.1612" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
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<a id="Kondo2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kondo, H., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K.
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<strong>Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.</strong>
|
|
Brit. J. Ophthal. 87: 1291-1295, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14507768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14507768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14507768[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=14507768" 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/bjo.87.10.1291" target="_blank">Full Text</a>]
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</p>
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<a id="5" class="mim-anchor"></a>
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<a id="MacDonald2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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MacDonald, M. L. E., Goldberg, Y. P., MacFarlane, J., Samuels, M. E., Trese, M. T., Shastry, B. S.
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<strong>Genetic variants of frizzled-4 gene in familial exudative vitreoretinopathy and advanced retinopathy of prematurity. (Letter)</strong>
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Clin. Genet. 67: 363-366, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15733276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15733276</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15733276" 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.1399-0004.2005.00408.x" target="_blank">Full Text</a>]
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</p>
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<a id="6" class="mim-anchor"></a>
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<a id="Qin2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H.
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<strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong>
|
|
Hum. Mutat. 26: 104-112, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15981244" 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.20191" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Qin2008" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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Qin, M., Kondo, H., Tahira, T., Hayashi, K.
|
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<strong>Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy.</strong>
|
|
Hum. Genet. 122: 615-623, 2008.
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17955262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17955262</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17955262" 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/10.1007/s00439-007-0438-8" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Robitaille2002" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
|
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Robitaille, J., MacDonald, M. L. E., Kaykas, A., Sheldahl, L. C., Zeisler, J., Dube, M.-P., Zhang, L.-H., Singaraja, R. R., Guernsey, D. L., Zhang, B., Siebert, L. F., Hoskin-Mott, A., Trese, M. T., Pimstone, S. N., Shastry, B. S., Moon, R. T., Hayden, M. R., Goldberg, Y. P., Samuels, M. E.
|
|
<strong>Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.</strong>
|
|
Nature Genet. 32: 326-330, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12172548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12172548</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12172548" 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/ng957" target="_blank">Full Text</a>]
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|
|
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|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
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<a id="Sagara2001" class="mim-anchor"></a>
|
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<div class="">
|
|
<p class="mim-text-font">
|
|
Sagara, N., Kirikoshi, H., Terasaki, H., Yasuhiko, Y., Toda, G., Shiokawa, K., Katoh, M.
|
|
<strong>FZD4S, a splicing variant of frizzled-4, encodes a soluble-type positive regulator of the WNT signaling pathway.</strong>
|
|
Biochem. Biophys. Res. Commun. 282: 750-756, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11401527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11401527</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11401527" 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/10.1006/bbrc.2001.4634" target="_blank">Full Text</a>]
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|
|
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|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
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<a id="Xu2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Xu, Q., Wang, Y., Dabdoub, A., Smallwood, P. M., Williams, J., Woods, C., Kelley, M. W., Jiang, L., Tasman, W., Zhang, K., Nathans, J.
|
|
<strong>Vascular development in the retina and inner ear: control by norrin and frizzled-4, a high-affinity ligand-receptor pair.</strong>
|
|
Cell 116: 883-895, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15035989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15035989</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15035989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0092-8674(04)00216-8" target="_blank">Full Text</a>]
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|
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|
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|
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|
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<a id="Yang2018" class="mim-anchor"></a>
|
|
<div class="">
|
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<p class="mim-text-font">
|
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Yang, S., Wu, Y., Xu, T.-H., de Waal, P. W., He, Y., Pu, M., Chen, Y., DeBruine, Z. J., Zhang, B., Zaidi, S. A., Popov, P., Guo, Y., and 13 others.
|
|
<strong>Crystal structure of the Frizzled 4 receptor in a ligand-free state.</strong>
|
|
Nature 560: 666-670, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30135577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30135577</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30135577" 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/s41586-018-0447-x" target="_blank">Full Text</a>]
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<a id="Yao2004" class="mim-anchor"></a>
|
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<div class="">
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Yao, R., Natsume, Y., Noda, T.
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<strong>MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap.</strong>
|
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Oncogene 23: 6023-6030, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15195140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15195140</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15195140" 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/sj.onc.1207817" target="_blank">Full Text</a>]
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<a id="Yoshida2004" class="mim-anchor"></a>
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Yoshida, S., Arita, R.-I., Yoshida, A., Tada, H., Emori, A., Noda, Y., Nakao, S., Fujisawa, K., Ishibashi, T.
|
|
<strong>Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative vitreoretinopathy.</strong>
|
|
Am. J. Ophthal. 138: 670-671, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15488808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15488808</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15488808" 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.ajo.2004.05.001" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 11/19/2018
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 08/15/2014<br>Marla J. F. O'Neill - updated : 3/12/2008<br>Jane Kelly - updated : 9/13/2006<br>Cassandra L. Kniffin - updated : 8/14/2006<br>Stylianos E. Antonarakis - updated : 4/13/2004<br>Patricia A. Hartz - updated : 3/10/2004<br>Ada Hamosh - updated : 9/25/2003<br>Victor A. McKusick - updated : 8/19/2002
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<span class="text-nowrap mim-text-font">
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Creation Date:
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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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Paul J. Converse : 2/19/2000
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/11/2019
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<span class="mim-text-font">
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carol : 11/20/2018<br>alopez : 11/19/2018<br>mgross : 08/15/2014<br>wwang : 6/9/2011<br>wwang : 3/17/2008<br>terry : 3/12/2008<br>terry : 9/18/2007<br>carol : 7/27/2007<br>carol : 9/13/2006<br>wwang : 8/23/2006<br>wwang : 8/23/2006<br>ckniffin : 8/14/2006<br>wwang : 11/17/2005<br>mgross : 4/13/2004<br>mgross : 3/24/2004<br>mgross : 3/24/2004<br>terry : 3/10/2004<br>tkritzer : 9/30/2003<br>terry : 9/25/2003<br>alopez : 10/18/2002<br>alopez : 8/20/2002<br>terry : 8/19/2002<br>carol : 2/19/2000
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<h3>
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<span class="mim-font">
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<strong>*</strong> 604579
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</h3>
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<h3>
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<span class="mim-font">
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FRIZZLED CLASS RECEPTOR 4; FZD4
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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FRIZZLED, DROSOPHILA, HOMOLOG OF, 4
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: FZD4</em></strong>
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</span>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 415297005;
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<strong>ICD10CM:</strong> H35.1, H35.10, H35.17;
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<strong>ICD9CM:</strong> 362.20, 362.21;
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<strong>
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<em>
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Cytogenetic location: 11q14.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 11:86,945,679-86,955,395 </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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<span class="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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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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</th>
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Phenotype <br /> MIM number
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<th>
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Inheritance
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<th>
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Phenotype <br /> mapping key
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<td rowspan="2">
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<span class="mim-font">
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11q14.2
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<span class="mim-font">
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Exudative vitreoretinopathy 1
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<span class="mim-font">
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133780
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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Retinopathy of prematurity
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<span class="mim-font">
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133780
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<td>
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<span class="mim-font">
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Autosomal dominant
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<td>
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<span class="mim-font">
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3
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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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</div>
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<span class="mim-text-font">
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<p>Members of the 'frizzled' (FZ) gene family (see 606143) encode 7-transmembrane domain proteins that are receptors for Wnt (see Wnt5A; 164975) signaling proteins.</p>
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</span>
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<div>
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<br />
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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>By screening a human fetal lung cDNA library with an FZD4 cDNA fragment isolated from a human gastric cancer cDNA pool, Kirikoshi et al. (1999) obtained a full-length cDNA of FZD4. FZD4 encodes a deduced 537-amino acid protein that has a cysteine-rich domain (CRD) in the N-terminal extracellular region, 2 cysteine residues in the second and third extracellular loops, 2 extracellular N-linked glycosylation sites, and the S/T-X-V motif in the C terminus. Amino acid sequence identity with other FZD proteins ranged from 39 to 52% in the N terminus to 42 to 69% in the transmembrane domains. Northern blot analysis revealed expression of a 7.7-kb transcript in large amounts in adult heart, skeletal muscle, ovary, and fetal kidney, in moderate amounts in adult liver, kidney, pancreas, spleen, and fetal lung, and in small amounts in placenta, adult lung, prostate, testis, colon, fetal brain, and liver. Expression was also strong in HeLa cells but not in several cancer cell lines. </p><p>By screening a fetal lung cDNA library using the C terminus of FZD4 as probe, followed by PCR of a fetal kidney cDNA library, Sagara et al. (2001) cloned an FZD4 variant, which they called FZD4S. FZD4S is unspliced and includes exon 1, intron 1, and exon 2. The deduced protein contains only 125 amino acids due to the introduction of a stop codon within the retained intron. The N-terminal 98 amino acids of FZD4S are identical to those of the full-length FZD4 protein, but the last 27 residues are unique. Compared with FZD4, FZD4S retains the N-terminal signal peptide and the N-terminal part of the CRD, but not the latter half of the CRD or the 7 transmembrane domains, indicating that FZD4S is likely to be a soluble protein. Northern blot analysis detected modest expression of a 10.0-kb mRNA in fetal kidney and faint expression in adult heart and fetal lung. RNA dot blot analysis detected expression in adult heart and lung and in fetal kidney and lung. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Sagara et al. (2001) injected synthetic FZD4S mRNA into the ventral marginal zone of Xenopus embryos at the 4-cell stage. The injected FZD4S did not induce axis duplication by itself, but augmented the axis duplication potential of coinjected Xenopus Wnt8 (see 601396) mRNA. Sagara et al. (2001) concluded that the FZD4S variant of FZD4 is a soluble protein that can activate the WNT signaling pathway. </p><p>The findings of Robitaille et al. (2002) supported a function for FZD4 in retinal angiogenesis. Robitaille et al. (2002) injected Xenopus laevis embryos with wildtype and familial exudative vitreoretinopathy (FEVR; 133780)-associated FZD4 mutants. They found that wildtype FZD4, but not mutant FZD4, activated CAMK2 (see 114078) and PKC (see 176960), components of the Wnt/Ca(2+) signaling pathway. </p><p>Chen et al. (2003) found that endocytosis of FZD4 in human embryonic kidney cells was dependent on added WNT5A protein and was accomplished by the multifunctional adaptor protein beta-arrestin-2 (107941), which was recruited to FZD4 by binding to phosphorylated dishevelled-2 (DVL2; 602151). The authors concluded that their findings provided a previously unrecognized mechanism for receptor recruitment of beta-arrestin and demonstrated that dishevelled plays an important role in the endocytosis of frizzled, as well as in promoting signaling. </p><p>Using a complementation assay, Kaykas et al. (2004) found that FZD4 could form homodimers. It could also form heterodimers with other FZD proteins, including rat Fzd1 (603408), rat Fzd2 (600667), Xenopus Fzd7 (603410), and human FZD9 (601766). Strongest affinity was displayed by proteins with similar amino acid sequence. Kaykas et al. (2004) found that an FEVR-associated FZD4 mutant with a frameshift at leu501 (604579.0002), which does not accumulate at the plasma membrane, was trapped in the endoplasmic reticulum. Through heterodimerization, this mutant FZD4 could trap wildtype FZD4 and inhibit its signaling. </p><p>Incomplete retinal vascularization occurs in both Norrie disease (310600) and FEVR. Norrin, the protein product of the NDP gene (300658), is a secreted protein. One form of FEVR is caused by defects in FZD4, a presumptive Wnt receptor. Xu et al. (2004) determined that norrin and FZD4 function as a ligand-receptor pair based on the similarity in vascular phenotypes caused by norrin and FZD4 mutations in humans and mice; the specificity and high affinity of norrin-FZD4 binding; the high efficiency with which norrin induces FZD4- and LRP (see 107770)-dependent activation of the classical Wnt pathway; and the signaling defects displayed by disease-associated variants of norrin and FZD4. These data defined a norrin-FZD4 signaling system that plays a central role in vascular development in the eye and ear, and they indicated that ligands unrelated to Wnts can act through frizzled receptors. </p><p>Using yeast 2-hybrid assays, Yao et al. (2004) found that PDZ domain 1 of mouse Magi3 (615943) interacted with the C-terminal PDZ-binding motifs of Fzd4 and Fzd7. PDZ domain 1 also interacted with Ltap (VANGL2; 600533), another planar cell polarity signaling protein. Magi3, Fzd4, and Ltap independently localized to sites of cell-cell contacts in epithelial cells, and these 3 proteins interacted in a complex that required Magi3. Magi3 strongly enhanced Rac (see 602048)-dependent Jnk (see 601158) activation by Fzd4 and Ltap. </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 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>Kirikoshi et al. (1999) determined that the FZD4 gene contains 2 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>Biochemical Features</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Yang et al. (2018) presented the atomic-resolution structure of the human FZD4 transmembrane domain in the absence of a bound ligand. The structure revealed an unusual transmembrane architecture in which helix VI is short and tightly packed, and is distinct from all other GPCR structures reported so far. Within this unique transmembrane fold is an extremely narrow and highly hydrophilic pocket that is not amenable to the binding of traditional GPCR ligands. Yang et al. (2018) showed that such a pocket is conserved across all FZDs, which may explain the long-standing difficulties in the development of ligands for these receptors. Molecular dynamics simulations on the microsecond timescale and mutational analysis uncovered 2 coupled, dynamic kinks located at helix VII that are involved in FZD4 activation. The stability of the structure in its ligand-free form, an unfavorable pocket for ligand binding, and the 2 unusual kinks on helix VII suggested that FZDs may have evolved a novel ligand recognition and activation mechanism that is distinct from that of other GPCRs. </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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<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 FISH, Kirikoshi et al. (1999) mapped the FZD4 gene to chromosome 11q14-q21. By positional cloning, Robitaille et al. (2002) mapped the FZD4 gene to chromosome 11q14.2. </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 affected members of 2 unrelated families with autosomal dominant familial exudative vitreoretinopathy (EVR1; 133780), Robitaille et al. (2002) identified 2 different heterozygous deletions in exon 2 of the FZD4 gene (604579.0001; 604579.0002). Both mutations altered the seventh transmembrane domain and the intracellular carboxy-terminal tail, respectively. No mutations in FZD4 were detected in 3 other small families with FEVR. Robitaille et al. (2002) presented data indicating that the changes in FZD4 in these families with autosomal dominant FEVR represented loss-of-function mutations. Following transfection in COS-7 cells, wildtype FZD4 and the FEVR-related FZD4 mutant lacking met493 and trp494 accumulated at the plasma membrane; however, the mutant containing the frameshift at leu501 did not. </p><p>In an infant with advanced retinopathy of prematurity (see 133780), MacDonald et al. (2005) identified heterozygosity for a missense mutation in the FZD4 gene (604579.0006). </p>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using a norrin-based reporter assay to analyze the effects of FEVR-causing mutations, Qin et al. (2008) demonstrated that a nonsense mutation in FZD4 completely abolished signaling activity, whereas missense mutations in FZD4 and LRP5 (603506) caused a moderate level of reduction, and a double missense mutation in both genes caused a severe reduction in activity, correlating roughly with clinical phenotypes. Norrin mutants, however, showed variable effects on signal transduction, and no correlation with clinical phenotypes was observed; norrin mutants also showed impaired cell surface binding. Qin et al. (2008) concluded that norrin signaling is involved in FEVR pathogenesis, but suggested the presence of an unknown parallel pathway at the level of receptor/ligand binding as evidenced by the moderate and variable signal reduction lacking a clear genotype/phenotype correlation. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 EXUDATIVE VITREORETINOPATHY 1</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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FZD4, 6-BP DEL, NT1479
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<br />
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SNP: rs80358301,
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ClinVar: RCV000005818, RCV000478323
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a large Canadian kindred of British descent with exudative vitreoretinopathy (EVR1; 133780), Robitaille et al. (2002) demonstrated that affected members had a mutation in the FZD4 gene: deletion of nucleotides 1479-1484, resulting in deletion of 2 highly conserved amino acids, met493 and trp494. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 EXUDATIVE VITREORETINOPATHY 1</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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FZD4, 2-BP DEL, 1501CT
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<br />
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SNP: rs80358303,
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ClinVar: RCV000005819, RCV001091739
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family of European descent with exudative vitreoretinopathy (EVR1; 133780), Robitaille et al. (2002) demonstrated that affected members carried a 2-bp deletion in the FZD4 gene, resulting in frameshift at leu501, creating a stop codon at residue 533. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 EXUDATIVE VITREORETINOPATHY 1</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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EXUDATIVE VITREORETINOPATHY, DIGENIC, INCLUDED
|
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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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FZD4, ARG417GLN
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<br />
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SNP: rs80358294,
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gnomAD: rs80358294,
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ClinVar: RCV000005820, RCV000005821
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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 patients with exudative vitreoretinopathy (EVR1; 133780), Kondo et al. (2003) identified a heterozygous 1250G-A transition in exon 2 of the FZD4 gene, resulting in an arg417-to-gln (R417Q) substitution. </p><p>Qin et al. (2005) reported a Japanese family with digenic inheritance of EVR. Affected members had a heterozygous R417Q mutation in the FZD4 gene consistent with EVR1 and a heterozygous mutation in the LRP5 gene (R444C; 603506.0026) consistent with EVR4 (601813). The 2 mutations cosegregated in the family, indicating that both mutations were located on the same chromosome consistent with digenic inheritance. The ocular phenotype in this family tended to be more severe compared to that of the family reported by Kondo et al. (2003) with the FZD4 R417Q mutation alone. </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>
|
|
<span class="mim-font">
|
|
<strong>.0004 EXUDATIVE VITREORETINOPATHY 1</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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FZD4, MET342VAL
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<br />
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|
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SNP: rs80358293,
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|
|
gnomAD: rs80358293,
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|
|
ClinVar: RCV000005822, RCV003555930
|
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese girl with exudative vitreoretinopathy (EVR1; 133780), Yoshida et al. (2004) identified a heterozygous 1026A-G transition in the FZD4 gene, resulting in a met342-to-val (M342V) substitution. She had esotropia and exudative retinal detachment at age 3 years. Her asymptomatic father, who also carried the mutation, was found to have bilateral avascular areas in the peripheral retina. </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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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 EXUDATIVE VITREORETINOPATHY 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
FZD4, TRP335CYS
|
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|
|
<br />
|
|
|
|
SNP: rs80358292,
|
|
|
|
|
|
|
|
ClinVar: RCV000005823
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese infant with exudative vitreoretinopathy (EVR1; 133780) and bilateral retinal folds, Qin et al. (2005) identified a heterozygous 1005G-C transversion in exon 2 of the FZD4 gene, resulting in a trp335-to-cys (W335C) substitution. The child's asymptomatic mother, who also carried the mutation, exhibited bilateral peripheral retinal avascularization with vascular tortuosity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 RETINOPATHY OF PREMATURITY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FZD4, ILE256VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894223,
|
|
|
|
|
|
gnomAD: rs104894223,
|
|
|
|
|
|
ClinVar: RCV000005824, RCV001262378, RCV001493514, RCV004757098
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant with advanced retinopathy of prematurity (see 133780), MacDonald et al. (2005) identified heterozygosity for a 766A-G transition in the FZD4 gene, resulting in an ile256-to-val (I256V) substitution. The mutation was not observed in 200 normal chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
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|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, W., ten Berge, D., Brown, J., Ahn, S., Hu, L. A., Miller, W. E., Caron, M. G., Barak, L. S., Nusse, R., Lefkowitz, R. J.
|
|
<strong>Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of frizzled 4.</strong>
|
|
Science 301: 1391-1394, 2003.
|
|
|
|
|
|
[PubMed: 12958364]
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|
|
[Full Text: https://doi.org/10.1126/science.1082808]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kaykas, A., Yang-Snyder, J., Heroux, M., Shah, K. V., Bouvier, M., Moon, R. T.
|
|
<strong>Mutant frizzled 4 associated with vitreoretinopathy traps wild-type frizzled in the endoplasmic reticulum by oligomerization.</strong>
|
|
Nature Cell Biol. 6: 52-58, 2004.
|
|
|
|
|
|
[PubMed: 14688793]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ncb1081]
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Kirikoshi, H., Sagara, N., Koike, J., Tanaka, K., Sekihara, H., Hirai, M., Katoh, M.
|
|
<strong>Molecular cloning and characterization of human frizzled-4 on chromosome 11q14-q21.</strong>
|
|
Biochem. Biophys. Res. Commun. 264: 955-961, 1999.
|
|
|
|
|
|
[PubMed: 10544037]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1999.1612]
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</p>
|
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</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Kondo, H., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K.
|
|
<strong>Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.</strong>
|
|
Brit. J. Ophthal. 87: 1291-1295, 2003.
|
|
|
|
|
|
[PubMed: 14507768]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bjo.87.10.1291]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
MacDonald, M. L. E., Goldberg, Y. P., MacFarlane, J., Samuels, M. E., Trese, M. T., Shastry, B. S.
|
|
<strong>Genetic variants of frizzled-4 gene in familial exudative vitreoretinopathy and advanced retinopathy of prematurity. (Letter)</strong>
|
|
Clin. Genet. 67: 363-366, 2005.
|
|
|
|
|
|
[PubMed: 15733276]
|
|
|
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|
[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00408.x]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H.
|
|
<strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong>
|
|
Hum. Mutat. 26: 104-112, 2005.
|
|
|
|
|
|
[PubMed: 15981244]
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|
|
[Full Text: https://doi.org/10.1002/humu.20191]
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</p>
|
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</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Qin, M., Kondo, H., Tahira, T., Hayashi, K.
|
|
<strong>Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy.</strong>
|
|
Hum. Genet. 122: 615-623, 2008.
|
|
|
|
|
|
[PubMed: 17955262]
|
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|
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|
|
[Full Text: https://doi.org/10.1007/s00439-007-0438-8]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Robitaille, J., MacDonald, M. L. E., Kaykas, A., Sheldahl, L. C., Zeisler, J., Dube, M.-P., Zhang, L.-H., Singaraja, R. R., Guernsey, D. L., Zhang, B., Siebert, L. F., Hoskin-Mott, A., Trese, M. T., Pimstone, S. N., Shastry, B. S., Moon, R. T., Hayden, M. R., Goldberg, Y. P., Samuels, M. E.
|
|
<strong>Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.</strong>
|
|
Nature Genet. 32: 326-330, 2002.
|
|
|
|
|
|
[PubMed: 12172548]
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|
|
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|
|
[Full Text: https://doi.org/10.1038/ng957]
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</p>
|
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</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Sagara, N., Kirikoshi, H., Terasaki, H., Yasuhiko, Y., Toda, G., Shiokawa, K., Katoh, M.
|
|
<strong>FZD4S, a splicing variant of frizzled-4, encodes a soluble-type positive regulator of the WNT signaling pathway.</strong>
|
|
Biochem. Biophys. Res. Commun. 282: 750-756, 2001.
|
|
|
|
|
|
[PubMed: 11401527]
|
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|
|
[Full Text: https://doi.org/10.1006/bbrc.2001.4634]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Xu, Q., Wang, Y., Dabdoub, A., Smallwood, P. M., Williams, J., Woods, C., Kelley, M. W., Jiang, L., Tasman, W., Zhang, K., Nathans, J.
|
|
<strong>Vascular development in the retina and inner ear: control by norrin and frizzled-4, a high-affinity ligand-receptor pair.</strong>
|
|
Cell 116: 883-895, 2004.
|
|
|
|
|
|
[PubMed: 15035989]
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|
|
[Full Text: https://doi.org/10.1016/s0092-8674(04)00216-8]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Yang, S., Wu, Y., Xu, T.-H., de Waal, P. W., He, Y., Pu, M., Chen, Y., DeBruine, Z. J., Zhang, B., Zaidi, S. A., Popov, P., Guo, Y., and 13 others.
|
|
<strong>Crystal structure of the Frizzled 4 receptor in a ligand-free state.</strong>
|
|
Nature 560: 666-670, 2018.
|
|
|
|
|
|
[PubMed: 30135577]
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|
|
[Full Text: https://doi.org/10.1038/s41586-018-0447-x]
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Yao, R., Natsume, Y., Noda, T.
|
|
<strong>MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap.</strong>
|
|
Oncogene 23: 6023-6030, 2004.
|
|
|
|
|
|
[PubMed: 15195140]
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|
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|
|
|
[Full Text: https://doi.org/10.1038/sj.onc.1207817]
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|
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Yoshida, S., Arita, R.-I., Yoshida, A., Tada, H., Emori, A., Noda, Y., Nakao, S., Fujisawa, K., Ishibashi, T.
|
|
<strong>Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative vitreoretinopathy.</strong>
|
|
Am. J. Ophthal. 138: 670-671, 2004.
|
|
|
|
|
|
[PubMed: 15488808]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajo.2004.05.001]
|
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|
|
</p>
|
|
</li>
|
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|
|
</ol>
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
|
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|
|
</div>
|
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|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 11/19/2018<br>Patricia A. Hartz - updated : 08/15/2014<br>Marla J. F. O'Neill - updated : 3/12/2008<br>Jane Kelly - updated : 9/13/2006<br>Cassandra L. Kniffin - updated : 8/14/2006<br>Stylianos E. Antonarakis - updated : 4/13/2004<br>Patricia A. Hartz - updated : 3/10/2004<br>Ada Hamosh - updated : 9/25/2003<br>Victor A. McKusick - updated : 8/19/2002
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
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Paul J. Converse : 2/19/2000
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carol : 09/11/2019<br>carol : 11/20/2018<br>alopez : 11/19/2018<br>mgross : 08/15/2014<br>wwang : 6/9/2011<br>wwang : 3/17/2008<br>terry : 3/12/2008<br>terry : 9/18/2007<br>carol : 7/27/2007<br>carol : 9/13/2006<br>wwang : 8/23/2006<br>wwang : 8/23/2006<br>ckniffin : 8/14/2006<br>wwang : 11/17/2005<br>mgross : 4/13/2004<br>mgross : 3/24/2004<br>mgross : 3/24/2004<br>terry : 3/10/2004<br>tkritzer : 9/30/2003<br>terry : 9/25/2003<br>alopez : 10/18/2002<br>alopez : 8/20/2002<br>terry : 8/19/2002<br>carol : 2/19/2000
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