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Entry
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- *136132 - FLAVIN-CONTAINING DIMETHYLANILINE MONOOXYGENASE 3; FMO3
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- OMIM
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<p>
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<span class="h4">*136132</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/136132">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000007933;t=ENST00000367755" 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=2328" 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=136132" 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 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=ENSG00000007933;t=ENST00000367755" 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_001002294,NM_001319173,NM_001319174,NM_006894,XM_047416207" 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_001002294" 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=136132" 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=00633&isoform_id=00633_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/FMO3" 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/188631,623240,6166183,21594874,50541961,50541965,58102139,62897893,119611292,119611293,119611294,189053761,221041162,221042204,957949429,957949432,983616511,983616513,2217265677,2462506873" 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/P31513" 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=2328" 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=ENSG00000007933;t=ENST00000367755" 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=FMO3" 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=FMO3" 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+2328" 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/FMO3" 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:2328" 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/2328" 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=chr1&hgg_gene=ENST00000367755.9&hgg_start=171090905&hgg_end=171117819&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/genes/HGNC:3771" 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/fmo3" 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=136132[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=136132[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/ENSG00000007933" 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=FMO3" 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=FMO3" 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=FMO3" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://human-fmo3.biochem.ucl.ac.uk/Human_FMO3/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=FMO3&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/PA166" 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:3771" 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/FBgn0033079.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:1100496" 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/FMO3#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:1100496" 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/2328/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://omia.org/OMIA001360/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=2328" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001476;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001476 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001477;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001477 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001478;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001478 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001479;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001479 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001480;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001480 </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 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:2328" 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=FMO3&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> 237959005<br />
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<strong>ICD10CM:</strong> E72.52<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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136132
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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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FLAVIN-CONTAINING DIMETHYLANILINE MONOOXYGENASE 3; FMO3
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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>
|
|
<span class="mim-font">
|
|
FLAVIN-CONTAINING MONOOXYGENASE 3
|
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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=FMO3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FMO3</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/1/1413?start=-3&limit=10&highlight=1413">1q24.3</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:171090905-171117819&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">1:171,090,905-171,117,819</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>
|
|
<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
|
|
Location
|
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</th>
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<th>
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Phenotype
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</th>
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
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<th>
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/1413?start=-3&limit=10&highlight=1413">
|
|
1q24.3
|
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</a>
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Trimethylaminuria
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/602079"> 602079 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<p>The mammalian flavin-containing monooxygenases (FMO; <a href="https://enzyme.expasy.org/EC/1.14.13.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.14.13.8</a>) represent a multigene family whose gene products are localized in the endoplasmic reticulum of many tissues. These enzymes catalyze the NADPH-dependent oxidative metabolism of many drugs, pesticides, and other foreign compounds. Their substrates are soft nucleophiles with an electron-rich center, typically a nitrogen, sulfur or phosphorus-containing functional group, as the site for oxidative attack by the enzyme (<a href="#24" class="mim-tip-reference" title="Ziegler, D. M. <strong>Flavin-containing monooxygenases: enzymes adapted for multisubstrate specificity.</strong> Trends Pharm. Sci. 11: 321-324, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2203193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2203193</a>] [<a href="https://doi.org/10.1016/0165-6147(90)90235-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2203193">Ziegler, 1990</a>; <a href="#14" class="mim-tip-reference" title="Hines, R. N, Cashman, J. R., Philpot, R. M., Williams, D. E., Ziegler, D. M. <strong>The mammalian flavin-containing monooxygenases: molecular characterization and regulation of expression.</strong> Toxicol. Appl. Pharm. 125: 1-6, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8128486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8128486</a>] [<a href="https://doi.org/10.1006/taap.1994.1042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8128486">Hines et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8128486+2203193" 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="#17" class="mim-tip-reference" title="Lomri, N., Gu, Q., Cashman, J. R. <strong>Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver.</strong> Proc. Nat. Acad. Sci. 89: 1685-1689, 1992. Note: Erratum: Proc. Nat. Acad. Sci. 92: 9910 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1542660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1542660</a>] [<a href="https://doi.org/10.1073/pnas.89.5.1685" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1542660">Lomri et al. (1992)</a> isolated a full-length cDNA sequence for FMO3, which they designated FMO II, from an adult human liver cDNA library. This cDNA encoded a deduced 533-amino acid protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1542660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Dolphin, C. T., Cullingford, T. E., Shephard, E. A., Smith, R. L., Phillips, I. R. <strong>Differential developmental and tissue-specific regulation of expression of the genes encoding three members of the flavin-containing monooxygenase family of man, FMO1, FMO3 and FMO4.</strong> Europ. J. Biochem. 235: 683-689, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8654418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8654418</a>] [<a href="https://doi.org/10.1111/j.1432-1033.1996.00683.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8654418">Dolphin et al. (1996)</a> also isolated an FMO3 cDNA from a human liver library. This cDNA encoded a deduced 532-amino acid protein that shared 84% sequence identity with the rabbit FMO3 protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8654418" 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="#11" class="mim-tip-reference" title="Dolphin, C. T., Riley, J. H., Smith, R. L., Shephard, E. A., Phillips, I. R. <strong>Structural organization of the human flavin-containing monooxygenase 3 gene (FMO3), the favored candidate for fish-odor syndrome, determined directly from genomic DNA.</strong> Genomics 46: 260-267, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9417913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9417913</a>] [<a href="https://doi.org/10.1006/geno.1997.5031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9417913">Dolphin et al. (1997)</a> determined that the FMO3 gene contains 1 noncoding and 8 coding exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9417913" 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 use of PCR with DNAs from somatic cell hybrids, <a href="#21" class="mim-tip-reference" title="Shephard, E. A., Dolphin, C. T., Fox, M. F., Povey, S., Smith, R., Phillips, I. R. <strong>Localization of genes encoding three distinct flavin-containing monooxygenases to human chromosome 1q.</strong> Genomics 16: 85-89, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8486388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8486388</a>] [<a href="https://doi.org/10.1006/geno.1993.1144" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8486388">Shephard et al. (1993)</a> mapped the FMO3 gene to chromosome 1. FMO3 is probably located in a cluster with FMO1 (<a href="/entry/136130">136130</a>) and FMO4 (<a href="/entry/136131">136131</a>) at 1q23-q25. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8486388" 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 quantitative RNase protection assays, <a href="#19" class="mim-tip-reference" title="Phillips, I. R., Dolphin, C. T., Clair, P., Hadley, M. R., Hutt, A. J., McCombie, R. R., Smith, R. L., Shephard, E. A. <strong>The molecular biology of the flavin-containing monooxygenases of man.</strong> Chem. Biol. Interact. 96: 17-32, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720101</a>] [<a href="https://doi.org/10.1016/0009-2797(94)03580-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720101">Phillips et al. (1995)</a> and <a href="#8" class="mim-tip-reference" title="Dolphin, C. T., Cullingford, T. E., Shephard, E. A., Smith, R. L., Phillips, I. R. <strong>Differential developmental and tissue-specific regulation of expression of the genes encoding three members of the flavin-containing monooxygenase family of man, FMO1, FMO3 and FMO4.</strong> Europ. J. Biochem. 235: 683-689, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8654418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8654418</a>] [<a href="https://doi.org/10.1111/j.1432-1033.1996.00683.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8654418">Dolphin et al. (1996)</a> determined that FMO3 is present in low abundance in fetal liver and lung and in adult kidney and lung, and in much greater abundance in adult liver. They determined that FMO3 and FMO1 (<a href="/entry/136130">136130</a>) are subject to developmental and tissue-specific regulation and, in the liver, there is a developmental switch in the expression of these genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7720101+8654418" 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 Western blot analysis of human liver microsomal samples ranging from 8 weeks gestation to 18 years of age, <a href="#15" class="mim-tip-reference" title="Koukouritaki, S. B., Simpson, P., Yeung, C. K., Rettie, A. E., Hines, R. N. <strong>Human hepatic flavin-containing monooxygenases 1 (FMO1) and 3 (FMO3) developmental expression.</strong> Pediat. Res. 51: 236-243, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11809920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11809920</a>] [<a href="https://doi.org/10.1203/00006450-200202000-00018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11809920">Koukouritaki et al. (2002)</a> confirmed that FMO1 is the major fetal isoform and FMO3 is the major adult isoform. The highest level of FMO1 expression was observed in embryonic samples at 8 to 15 weeks of gestation; its expression was low, but detectable in most samples within the first 3 days of life, but then was extinguished in all but a few samples. In contrast, the onset of FMO3 expression was highly variable, with most individuals failing to express this isoform during the neonatal period. FMO3 was expressed at intermediate levels until 11 years of age when a gender-independent increase in FMO3 expression was observed during puberty. <a href="#15" class="mim-tip-reference" title="Koukouritaki, S. B., Simpson, P., Yeung, C. K., Rettie, A. E., Hines, R. N. <strong>Human hepatic flavin-containing monooxygenases 1 (FMO1) and 3 (FMO3) developmental expression.</strong> Pediat. Res. 51: 236-243, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11809920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11809920</a>] [<a href="https://doi.org/10.1203/00006450-200202000-00018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11809920">Koukouritaki et al. (2002)</a> observed pronounced interindividual variation of FMO3 protein levels from 2- to 20-fold. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11809920" 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="#20" class="mim-tip-reference" title="Phillips, I. R., Shephard, E. A. <strong>Flavin-containing monooxygenases: mutations, disease and drug response.</strong> Trends Pharm. Sci. 29: 294-301, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18423897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18423897</a>] [<a href="https://doi.org/10.1016/j.tips.2008.03.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18423897">Phillips and Shephard (2008)</a> noted that the delay between silencing of the FMO1 gene and the full activation of FMO3 means that during the first year of life many children have no, or very little, drug-metabolizing FMOs in their liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18423897" 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="#13" class="mim-tip-reference" title="Hernandez, D., Addou, S., Lee, D., Orengo, C., Shephard, E. A., Phillips, I. R. <strong>Trimethylaminuria and a human FMO3 mutation database.</strong> Hum. Mutat. 22: 209-213, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12938085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12938085</a>] [<a href="https://doi.org/10.1002/humu.10252" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12938085">Hernandez et al. (2003)</a> pointed out that compromised activity of FMO3 is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions in patients with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>) and in the general population. In addition to metabolizing the dietary-derived amine TMA, FMO3 catalyzes the NADPH-dependent oxidation of numerous foreign compounds, including therapeutic drugs such as the antiestrogen tamoxifen, the antifungal ketoconazole, and the nonsteroidal antiinflammatory drugs sulindac sulfide and benzydamine, as reviewed by <a href="#5" class="mim-tip-reference" title="Cashman, J. R., Zhang, J. <strong>Interindividual differences of human flavin-containing monooxygenase 3: genetic polymorphisms and functional variation.</strong> Drug Metab. Dispos. 30: 1043-1052, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12228178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12228178</a>] [<a href="https://doi.org/10.1124/dmd.30.10.1043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12228178">Cashman and Zhang (2002)</a>. Sufferers of trimethylaminuria may display a reduced ability to metabolize substrates for FMO3 such as nicotine (<a href="#4" class="mim-tip-reference" title="Ayesh, R., Al-Waiz, M., Crothers, M. J., Cholerton, S., Mitchell, S. C., Idle, J. R., Smith, R. L. <strong>Deficient nicotine N-oxidation in two sisters with trimethylaminuria.</strong> Brit. J. Clin. Pharm. 25: 664P only, 1988."None>Ayesh et al., 1988</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12228178+12938085" 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>FMO3 metabolizes a number of drugs, including amphetamine, clozapine, deprenyl, metamphetamine, tamoxifen, ethionamide, thiacetazone, and sulindac sulfide (see reviews by <a href="#16" class="mim-tip-reference" title="Krueger, S. K., Williams, D. E. <strong>Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism.</strong> Pharm. Ther. 106: 357-387, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15922018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15922018</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15922018[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.pharmthera.2005.01.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15922018">Krueger and Williams (2005)</a> and <a href="#20" class="mim-tip-reference" title="Phillips, I. R., Shephard, E. A. <strong>Flavin-containing monooxygenases: mutations, disease and drug response.</strong> Trends Pharm. Sci. 29: 294-301, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18423897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18423897</a>] [<a href="https://doi.org/10.1016/j.tips.2008.03.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18423897">Phillips and Shephard (2008)</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18423897+15922018" 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="#1" class="mim-tip-reference" title="Akerman, B. R., Chow, L., Forrest, S., Youil, R., Cashman, J., Treacy, E. P. <strong>Mutations in the flavin-containing monoxygenase (sic) form 3 (FMO3) gene cause trimethylaminuria, fish odour syndrome. (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A53 only, 1997."None>Akerman et al. (1997)</a> and <a href="#22" class="mim-tip-reference" title="Treacy, E. P., Akerman, B. R., Chow, L. M. L., Youil, R., Bibeau, C., Lin, J., Bruce, A. G., Knight, M., Danks, D. M., Cashman, J. R., Forrest, S. M. <strong>Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication.</strong> Hum. Molec. Genet. 7: 839-845, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9536088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9536088</a>] [<a href="https://doi.org/10.1093/hmg/7.5.839" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9536088">Treacy et al. (1998)</a> reported 3 different mutations in the FMO3 gene in Australian probands with trimethylaminuria (<a href="/entry/602079">602079</a>), or fish-odor syndrome, who shared a particular polymorphic haplotype. <a href="#22" class="mim-tip-reference" title="Treacy, E. P., Akerman, B. R., Chow, L. M. L., Youil, R., Bibeau, C., Lin, J., Bruce, A. G., Knight, M., Danks, D. M., Cashman, J. R., Forrest, S. M. <strong>Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication.</strong> Hum. Molec. Genet. 7: 839-845, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9536088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9536088</a>] [<a href="https://doi.org/10.1093/hmg/7.5.839" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9536088">Treacy et al. (1998)</a> showed that these mutations impair N-oxygenation of xenobiotics and are responsible for the trimethylaminuria phenotype. A nonsense mutation, glu305 to ter (E305X; <a href="#0001">136132.0001</a>), was found on 6 mutant chromosomes of British origin, homozygous in 1 and heterozygous in 4 individuals. Homozygosity for a missense mutation, val257 to met (V257M; <a href="#0002">136132.0002</a>), was found in 1 individual of Greek origin. Heterozygosity for a met66-to-ile (M66I; <a href="#0003">136132.0003</a>) mutation was found in 1 individual of Irish extraction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9536088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with trimethylaminuria, <a href="#9" class="mim-tip-reference" title="Dolphin, C. T., Janmohamed, A., Smith, R. L., Shephard, E. A., Phillips, I. R. <strong>Missense mutation in flavin-containing mono-oxygenase 3 gene, FMO3, underlies fish-odour syndrome.</strong> Nature Genet. 17: 491-494, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398858</a>] [<a href="https://doi.org/10.1038/ng1297-491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398858">Dolphin et al. (1997)</a> found a pro153-to-leu mutation in the FMO3 gene (P153L; <a href="#0004">136132.0004</a>) that abolished FMO3 catalytic activity. They demonstrated that FMO3 with the 551C-T mutation could not support the metabolism of dietary-derived trimethylamine (TMA). In addition to TMA, FMOs catalyze the oxidation of a range of structurally diverse compounds, including drugs, pesticides, and other xenobiotics. The authors commented that although patients with trimethylaminuria are apparently deficient in nicotine N-oxidation, a reaction catalyzed predominantly by FMO3, the pharmacologic and toxicologic significance of an inherited block in FMO3-mediated oxidative metabolism is unclear. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398858" 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="#22" class="mim-tip-reference" title="Treacy, E. P., Akerman, B. R., Chow, L. M. L., Youil, R., Bibeau, C., Lin, J., Bruce, A. G., Knight, M., Danks, D. M., Cashman, J. R., Forrest, S. M. <strong>Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication.</strong> Hum. Molec. Genet. 7: 839-845, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9536088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9536088</a>] [<a href="https://doi.org/10.1093/hmg/7.5.839" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9536088">Treacy et al. (1998)</a> found that nonsense and missense mutations in the FMO3 gene were associated with a severe trimethylaminuria phenotype and were also implicated in impaired metabolism of other nitrogen- and sulfur-containing substances, including biogenic amines, both clinically and when mutated proteins expressed from cDNA were studied in vitro. The findings illustrated the clinical role played by human FMO3 in the metabolism of xenobiotic substrates and endogenous amines. One patient of English-Irish extraction with severe hypertension was observed with blood pressure of 200/110 following the use of nasal epinephrine. Adverse tyramine reactions were observed in at least 3 patients. Urticaria and intolerance of sulfur-containing medication was observed in a patient homozygous for the P153L mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9536088" 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="Chung, W.-G., Cha, Y.-N. <strong>Oxidation of caffeine to theobromine and theophylline is catalyzed primarily by flavin-containing monooxygenase in liver microsomes.</strong> Biochem. Biophys. Res. Commun. 235: 685-688, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207220</a>] [<a href="https://doi.org/10.1006/bbrc.1997.6866" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9207220">Chung and Cha (1997)</a> showed that production of theobromine from caffeine is catalyzed primarily by the FMO present in adult human liver microsomes. They determined FMO activity in vivo noninvasively by taking the urinary molar concentration ratio of theobromine/caffeine in a Korean population. In 82 Korean volunteers, <a href="#18" class="mim-tip-reference" title="Park, C.-S., Chung, W.-G., Kang, J.-H., Roh, H.-K., Lee, K.-H., Cha, Y.-N. <strong>Phenotyping of flavin-containing monooxygenase using caffeine metabolism and genotyping of FMO3 gene in a Korean population.</strong> Pharmacogenetics 9: 155-164, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10376762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10376762</a>]" pmid="10376762">Park et al. (1999)</a> determined FMO activity by taking the molar concentration ratio of theobromine and caffeine present in the 1-hour urine (between 4 and 5 hours) samples collected after administration of a cup of coffee containing 110 mg of caffeine. Among 82 volunteers, there were 19 women and 63 men (30 smokers and 52 nonsmokers). Volunteers were divided into 2 groups comprising low (0.53-2.99) and high (3.18-11.95) FMO activities separated by an antimode of 3.18. Genomic DNAs from peripheral blood were amplified by PCR with oligonucleotides designed from intronic sequences of the human FMO3 gene. Comparing nucleotide sequences of the amplified FMO3 gene originating from randomly selected individuals with low and high FMO activities, 9 point mutations were identified in the open reading frame sequences. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10376762+9207220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Akerman, B. R., Lemass, H., Chow, L. M. L., Lambert, D. M., Greenberg, C., Bibeau, C., Mamer, O. A., Treacy, E. P. <strong>Trimethylaminuria is caused by mutations of the FMO3 gene in a North American cohort.</strong> Molec. Genet. Metab. 68: 24-31, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10479479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10479479</a>] [<a href="https://doi.org/10.1006/mgme.1999.2885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10479479">Akerman et al. (1999)</a> studied a cohort of North American individuals with severe trimethylaminuria, defined by a reduction of TMA oxidation below 50% of normal. They detected 4 novel FOM3 mutations, including 2 missense mutations, ala52 to thr (A52T; <a href="#0008">136132.0008</a>) and arg387 to leu (R387L; <a href="#0007">136132.0007</a>), and 1 nonsense mutation, glu314 to ter (E314X; <a href="#0009">136132.0009</a>). The fourth allele was apparently composed of 2 relatively common polymorphisms (lys158-gly308) found in the general population. For the E314X mutation, loss of activity was strongly predicted due to truncation of the FMO3 protein at codon 314, since deletion of even the final 30 amino acids of this 532-residue protein will ablate function in vitro. While the A52T and R387L mutations had not been expressed, they satisfied several conditions for designation as disease-causing: the changes were not observed in controls, they were nonconservative substitutions, and no other changes were identified in the probands when sequencing all expressed FMO3 exons. Furthermore, the A52T and R387L residues appear to be highly conserved within the FMO gene family. The authors suggested that the 2 common changes (lys158-gly308) in cis diminished the activity of the enzyme and rendered it incapable of compensating for the A52T mutation carried by the other allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10479479" 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="#13" class="mim-tip-reference" title="Hernandez, D., Addou, S., Lee, D., Orengo, C., Shephard, E. A., Phillips, I. R. <strong>Trimethylaminuria and a human FMO3 mutation database.</strong> Hum. Mutat. 22: 209-213, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12938085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12938085</a>] [<a href="https://doi.org/10.1002/humu.10252" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12938085">Hernandez et al. (2003)</a> described a human FMO3 mutation database. They indicated that 16 mutations (12 missense, 3 nonsense, and 1 gross deletion) were known to cause trimethylaminuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12938085" 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="#1" class="mim-tip-reference" title="Akerman, B. R., Chow, L., Forrest, S., Youil, R., Cashman, J., Treacy, E. P. <strong>Mutations in the flavin-containing monoxygenase (sic) form 3 (FMO3) gene cause trimethylaminuria, fish odour syndrome. (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A53 only, 1997."None>Akerman et al. (1997)</a> identified a glu305-to-ter (E305X) mutation in the FMO3 gene in 6 mutant chromosomes from Australian probands of British origin with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>). The mutation was homozygous in 1 and heterozygous in 4 individuals. The E305X homozygote had, in addition to trimethylaminuria, tachycardia and severe hypertension after eating cheese (which contains tyramine) and after using nasal epinephrine in the treatment of an epistaxis (<a href="#7" class="mim-tip-reference" title="Danks, D. M., Hammond, J., Faull, K., Burke, D., Halpern, B. <strong>Trimethylaminuria: diet does not always control the fishy odor. (Letter)</strong> New Eng. J. Med. 295: 962, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/987532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">987532</a>]" pmid="987532">Danks et al., 1976</a>). The FMO3 enzyme metabolizes tyramine. Mutant FMO3 cDNA for this mutation demonstrated loss of substrate activity for TMA and tyramine when expressed in E. coli. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=987532" 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 an Australian individual of Greek origin with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>), <a href="#1" class="mim-tip-reference" title="Akerman, B. R., Chow, L., Forrest, S., Youil, R., Cashman, J., Treacy, E. P. <strong>Mutations in the flavin-containing monoxygenase (sic) form 3 (FMO3) gene cause trimethylaminuria, fish odour syndrome. (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A53 only, 1997."None>Akerman et al. (1997)</a> found homozygosity for a val257-to-met (V257M) missense mutation in the FMO3 gene.</p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs72549323 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72549323;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/rs72549323?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=rs72549323" 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=rs72549323" 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=RCV000017699" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017699" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017699</a>
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<p>In an Australian individual of Irish origin with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>), <a href="#1" class="mim-tip-reference" title="Akerman, B. R., Chow, L., Forrest, S., Youil, R., Cashman, J., Treacy, E. P. <strong>Mutations in the flavin-containing monoxygenase (sic) form 3 (FMO3) gene cause trimethylaminuria, fish odour syndrome. (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A53 only, 1997."None>Akerman et al. (1997)</a> found a met66-to-ile (M66I) mutation in the FMO3 gene in heterozygous state. Mutant FMO3 cDNA containing the M66I substitution demonstrated loss of substrate activity for TMA and tyramine when expressed in E. coli.</p><p>In an Australian patient with trimethylaminuria, <a href="#2" class="mim-tip-reference" title="Akerman, B. R., Forrest, S., Chow, L., Youil, R., Knight, M., Treacy, E. P. <strong>Two novel mutations of the FMO3 gene in a proband with trimethylaminuria.</strong> Hum. Mutat. 13: 376-379, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10338091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10338091</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)13:5<376::AID-HUMU5>3.0.CO;2-A" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10338091">Akerman et al. (1999)</a> found compound heterozygosity for 2 missense mutations in the FMO3 gene: M66I and arg492 to trp (R492W; <a href="#0005">136132.0005</a>). The second of these mutations involved a hypermutable CpG site and was a nonconservative change in a highly conserved region of the FMO3 gene. Arg492 was conserved in all FMO isoforms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10338091" 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 TRIMETHYLAMINURIA</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> rs72549326 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72549326;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/rs72549326?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=rs72549326" 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=rs72549326" 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=RCV000017701 OR RCV002223760 OR RCV004755741" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017701, RCV002223760, RCV004755741" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017701...</a>
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<p>In a brother and sister with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>), <a href="#9" class="mim-tip-reference" title="Dolphin, C. T., Janmohamed, A., Smith, R. L., Shephard, E. A., Phillips, I. R. <strong>Missense mutation in flavin-containing mono-oxygenase 3 gene, FMO3, underlies fish-odour syndrome.</strong> Nature Genet. 17: 491-494, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398858</a>] [<a href="https://doi.org/10.1038/ng1297-491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398858">Dolphin et al. (1997)</a> identified a homozygous 551C-T transition in the FMO3 gene, changing a CCC proline triplet at codon 153 to a CTC leucine triplet (P153L). Their unaffected parents and a third sib were heterozygous for the mutation. The authors found the same mutation in 2 other trimethylaminuria kindreds, in which it also cosegregated with the disorder. In the first kindred studied, the leu153 allele was found to carry a polymorphism at codon 158, namely glu158. Among 30 unrelated, non-trimethylaminuric individuals, pro153 was found in all, whereas glu158 and lys158 occurred in frequencies of approximately 50% each. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398858" 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>.0005 TRIMETHYLAMINURIA</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> rs72549334 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72549334;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/rs72549334?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=rs72549334" 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=rs72549334" 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=RCV000017702 OR RCV003574701" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017702, RCV003574701" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017702...</a>
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<p>For discussion of the arg492-to-trp (R492W) mutation in the FMO3 gene that was found in compound heterozygous state in a patient with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>) by <a href="#2" class="mim-tip-reference" title="Akerman, B. R., Forrest, S., Chow, L., Youil, R., Knight, M., Treacy, E. P. <strong>Two novel mutations of the FMO3 gene in a proband with trimethylaminuria.</strong> Hum. Mutat. 13: 376-379, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10338091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10338091</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)13:5<376::AID-HUMU5>3.0.CO;2-A" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10338091">Akerman et al. (1999)</a>, see <a href="#0003">136132.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10338091" 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 FMO3 ACTIVITY, DECREASED</strong>
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FMO3, GLY148TER
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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> rs72549325 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72549325;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/rs72549325?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=rs72549325" 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=rs72549325" 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=RCV000017703 OR RCV003556036" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017703, RCV003556036" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017703...</a>
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<p><a href="#18" class="mim-tip-reference" title="Park, C.-S., Chung, W.-G., Kang, J.-H., Roh, H.-K., Lee, K.-H., Cha, Y.-N. <strong>Phenotyping of flavin-containing monooxygenase using caffeine metabolism and genotyping of FMO3 gene in a Korean population.</strong> Pharmacogenetics 9: 155-164, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10376762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10376762</a>]" pmid="10376762">Park et al. (1999)</a> determined FMO activity by taking the molar concentration ratio of theobromine and caffeine present in the 1-hour urine (between 4 and 5 hours) samples collected after administration of a cup of coffee containing 110 mg of caffeine. In an individual who had the second lowest FMO activity, they detected a missense mutation, 442G-T in exon 4, that yielded a premature TGA stop codon replacing glycine-148 (G148X). He had the mutation in heterozygous state. His mother also had the heterozygous stop codon and equally low FMO activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10376762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 TRIMETHYLAMINURIA</strong>
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FMO3, ARG387LEU
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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> rs72549331 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72549331;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/rs72549331?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=rs72549331" 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=rs72549331" 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=RCV000017704 OR RCV003398530" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017704, RCV003398530" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017704...</a>
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<p>In a Metis patient from Canada with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>), <a href="#3" class="mim-tip-reference" title="Akerman, B. R., Lemass, H., Chow, L. M. L., Lambert, D. M., Greenberg, C., Bibeau, C., Mamer, O. A., Treacy, E. P. <strong>Trimethylaminuria is caused by mutations of the FMO3 gene in a North American cohort.</strong> Molec. Genet. Metab. 68: 24-31, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10479479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10479479</a>] [<a href="https://doi.org/10.1006/mgme.1999.2885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10479479">Akerman et al. (1999)</a> found homozygosity for a G-to-T transversion at nucleotide 1160 of the FMO3 gene, resulting in an arg387-to-leu (R387L) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10479479" 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="0008" class="mim-anchor"></a>
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<strong>.0008 TRIMETHYLAMINURIA</strong>
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FMO3, ALA52THR
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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> rs72549321 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72549321;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/rs72549321?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=rs72549321" 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=rs72549321" 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=RCV000017700 OR RCV004700244" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017700, RCV004700244" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017700...</a>
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<p>In a North American patient with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>), <a href="#3" class="mim-tip-reference" title="Akerman, B. R., Lemass, H., Chow, L. M. L., Lambert, D. M., Greenberg, C., Bibeau, C., Mamer, O. A., Treacy, E. P. <strong>Trimethylaminuria is caused by mutations of the FMO3 gene in a North American cohort.</strong> Molec. Genet. Metab. 68: 24-31, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10479479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10479479</a>] [<a href="https://doi.org/10.1006/mgme.1999.2885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10479479">Akerman et al. (1999)</a> identified a G-to-A transition at nucleotide 154 of the FMO3 gene, resulting in an ala52-to-thr (A52T) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10479479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<strong>.0009 TRIMETHYLAMINURIA</strong>
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FMO3, GLU314TER
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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> rs72549330 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72549330;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/rs72549330?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=rs72549330" 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=rs72549330" 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=RCV000017705" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017705" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017705</a>
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<p>In a North American patient with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>), <a href="#3" class="mim-tip-reference" title="Akerman, B. R., Lemass, H., Chow, L. M. L., Lambert, D. M., Greenberg, C., Bibeau, C., Mamer, O. A., Treacy, E. P. <strong>Trimethylaminuria is caused by mutations of the FMO3 gene in a North American cohort.</strong> Molec. Genet. Metab. 68: 24-31, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10479479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10479479</a>] [<a href="https://doi.org/10.1006/mgme.1999.2885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10479479">Akerman et al. (1999)</a> identified a G-to-T transversion at nucleotide 940 of the FMO3 gene, resulting in a glu314-to-ter (E314X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10479479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0010" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0010 TRIMETHYLAMINURIA</strong>
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FMO3, ASN61SER
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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> rs72549322 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72549322;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/rs72549322?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=rs72549322" 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=rs72549322" 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=RCV000017706" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017706" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017706</a>
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<p><a href="#10" class="mim-tip-reference" title="Dolphin, C. T., Janmohamed, A., Smith, R. L., Shephard, E. A., Phillips, I. R. <strong>Compound heterozygosity for missense mutations in the flavin-containing monooxygenase 3 (FMO3) gene in patients with fish-odour syndrome.</strong> Pharmacogenetics 10: 799-807, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11191884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11191884</a>] [<a href="https://doi.org/10.1097/00008571-200012000-00005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11191884">Dolphin et al. (2000)</a> found 2 individuals with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>) who were compound heterozygous for the P153L missense mutation (<a href="#0004">136132.0004</a>) and a novel asn61-to-ser (N61S) mutation in the FMO3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11191884" 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="0011" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0011 TRIMETHYLAMINURIA</strong>
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FMO3, MET434ILE
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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> rs72549332 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72549332;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/rs72549332?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=rs72549332" 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=rs72549332" 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=RCV000017707 OR RCV003556037" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017707, RCV003556037" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017707...</a>
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</span>
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<p><a href="#10" class="mim-tip-reference" title="Dolphin, C. T., Janmohamed, A., Smith, R. L., Shephard, E. A., Phillips, I. R. <strong>Compound heterozygosity for missense mutations in the flavin-containing monooxygenase 3 (FMO3) gene in patients with fish-odour syndrome.</strong> Pharmacogenetics 10: 799-807, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11191884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11191884</a>] [<a href="https://doi.org/10.1097/00008571-200012000-00005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11191884">Dolphin et al. (2000)</a> found that a patient with trimethylaminuria (<a href="/entry/602079">602079</a>) was compound heterozygous for the R492W mutation (<a href="#0005">136132.0005</a>) and a novel met434-to-ile (M434I) mutation in the FMO3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11191884" 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="0012" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0012 TRIMETHYLAMINURIA</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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FMO3, 2-EX DEL
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</span>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000017708" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017708" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017708</a>
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</span>
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<p><a href="#12" class="mim-tip-reference" title="Forrest, S. M., Knight, M., Akerman, B. R., Cashman, J. R., Treacy, E. P. <strong>A novel deletion in the flavin-containing monooxygenase gene (FMO3) in a Greek patient with trimethylaminuria.</strong> Pharmacogenetics 11: 169-174, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11266081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11266081</a>] [<a href="https://doi.org/10.1097/00008571-200103000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11266081">Forrest et al. (2001)</a> described trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>) caused by a deletion of more than 12 kb in the FMO3 gene in a 15-year-old Australian male of Greek parents. The deletion began 328 bp upstream from exon 1; the 3-prime end of the deletion occurred in intron 2. The deletion was 12,226 bp long. Because of homozygosity for the FMO3 gene deletion, it was predicted that in addition to loss of monooxygenase function for human FMO3 substrates, such as trimethylamine and other amines, the proband would exhibit decreased tolerance of biogenic amines, both medicinal and dietary. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11266081" 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="0013" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0013 TRIMETHYLAMINURIA</strong>
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</span>
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</h4>
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FMO3, GLU32LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs72549320 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72549320;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=rs72549320" 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=rs72549320" 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=RCV000017709" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017709" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017709</a>
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</span>
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<span class="mim-text-font">
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<p>In a patient with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>), <a href="#23" class="mim-tip-reference" title="Zhang, J., Tran, Q., Lattard, V., Cashman, J. R. <strong>Deleterious mutations in the flavin-containing monooxygenase 3 (FMO3) gene causing trimethylaminuria.</strong> Pharmacogenetics 13: 495-500, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12893987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12893987</a>] [<a href="https://doi.org/10.1097/00008571-200308000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12893987">Zhang et al. (2003)</a> identified a glu32-to-lys (E32K) mutation in the FMO3 gene. Expression studies showed that the E32K mutation abrogated the catalytic activity of the enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12893987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<strong>.0014 TRIMETHYLAMINURIA</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000017710" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017710" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017710</a>
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<p>In an individual with trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>), <a href="#23" class="mim-tip-reference" title="Zhang, J., Tran, Q., Lattard, V., Cashman, J. R. <strong>Deleterious mutations in the flavin-containing monooxygenase 3 (FMO3) gene causing trimethylaminuria.</strong> Pharmacogenetics 13: 495-500, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12893987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12893987</a>] [<a href="https://doi.org/10.1097/00008571-200308000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12893987">Zhang et al. (2003)</a> identified compound heterozygosity for 2 mutations in the FMO3 gene: a P153L change (<a href="#0004">136132.0004</a>) and a 1-bp deletion (191delA) in exon 3 at codon 64. The deletion resulted in a frameshift and premature termination of the gene immediately after codon 65. Family pedigree analysis revealed that the 2 mutations were carried on different alleles in this individual. Both mutations abolished the catalytic activity of the enzyme, explaining the severe clinical expression of trimethylaminuria. The patient was examined at the age of 3 years, at which time he was found to have 61% unmetabolized trimethylamine in urine, compatible with severe trimethylaminuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12893987" 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>.0015 TRIMETHYLAMINURIA, MILD</strong>
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FMO3, GLU308GLY AND GLU158LYS
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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> rs2266780 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2266780;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/rs2266780?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=rs2266780" 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=rs2266780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <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> rs2266782 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2266782;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/rs2266782?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=rs2266782" 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=rs2266782" 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=RCV000017711 OR RCV000201276 OR RCV000201278 OR RCV000248637 OR RCV000254132 OR RCV000290538 OR RCV000361492 OR RCV001642531 OR RCV001668146 OR RCV002251938" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017711, RCV000201276, RCV000201278, RCV000248637, RCV000254132, RCV000290538, RCV000361492, RCV001642531, RCV001668146, RCV002251938" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017711...</a>
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<span class="mim-text-font">
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<p>In patients with mild trimethylaminuria (TMAU; <a href="/entry/602079">602079</a>), <a href="#25" class="mim-tip-reference" title="Zschocke, J., Kohlmueller, D., Quak, E., Meissner, T., Hoffmann, G. F., Mayatepek, E. <strong>Mild trimethylaminuria caused by common variants in FMO3 gene.</strong> Lancet 354: 834-835, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10485731/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10485731</a>] [<a href="https://doi.org/10.1016/s0140-6736(99)80019-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10485731">Zschocke et al. (1999)</a> identified compound heterozygosity for mutations in the FMO3 gene: a P151L substitution (<a href="#0004">136132.0004</a>) on one allele, and 2 common polymorphisms, glu308 to gly (E308G) and glu 158 to lys (E158K), on the other. <a href="#25" class="mim-tip-reference" title="Zschocke, J., Kohlmueller, D., Quak, E., Meissner, T., Hoffmann, G. F., Mayatepek, E. <strong>Mild trimethylaminuria caused by common variants in FMO3 gene.</strong> Lancet 354: 834-835, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10485731/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10485731</a>] [<a href="https://doi.org/10.1016/s0140-6736(99)80019-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10485731">Zschocke et al. (1999)</a> noted that homozygosity for the P151L mutation had been found to cause severe trimethylaminuria. They found that individuals homozygous for the variant allele with the 2 common polymorphisms had decreased TMA oxidation capacity (less than 50%) indicative of mild trimethylaminuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10485731" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span 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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<a id="Akerman1997" class="mim-anchor"></a>
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<p class="mim-text-font">
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Akerman, B. R., Chow, L., Forrest, S., Youil, R., Cashman, J., Treacy, E. P.
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<strong>Mutations in the flavin-containing monoxygenase (sic) form 3 (FMO3) gene cause trimethylaminuria, fish odour syndrome. (Abstract)</strong>
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Am. J. Hum. Genet. 61 (suppl.): A53 only, 1997.
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<a id="Akerman1999" class="mim-anchor"></a>
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Akerman, B. R., Forrest, S., Chow, L., Youil, R., Knight, M., Treacy, E. P.
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<strong>Two novel mutations of the FMO3 gene in a proband with trimethylaminuria.</strong>
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Hum. Mutat. 13: 376-379, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10338091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10338091</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10338091" 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/(SICI)1098-1004(1999)13:5<376::AID-HUMU5>3.0.CO;2-A" target="_blank">Full Text</a>]
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<a id="Akerman1999" class="mim-anchor"></a>
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Akerman, B. R., Lemass, H., Chow, L. M. L., Lambert, D. M., Greenberg, C., Bibeau, C., Mamer, O. A., Treacy, E. P.
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<strong>Trimethylaminuria is caused by mutations of the FMO3 gene in a North American cohort.</strong>
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Molec. Genet. Metab. 68: 24-31, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10479479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10479479</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10479479" 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/mgme.1999.2885" target="_blank">Full Text</a>]
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<a id="Ayesh1988" class="mim-anchor"></a>
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Ayesh, R., Al-Waiz, M., Crothers, M. J., Cholerton, S., Mitchell, S. C., Idle, J. R., Smith, R. L.
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<strong>Deficient nicotine N-oxidation in two sisters with trimethylaminuria.</strong>
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Brit. J. Clin. Pharm. 25: 664P only, 1988.
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<a id="Cashman2002" class="mim-anchor"></a>
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Cashman, J. R., Zhang, J.
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<strong>Interindividual differences of human flavin-containing monooxygenase 3: genetic polymorphisms and functional variation.</strong>
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Drug Metab. Dispos. 30: 1043-1052, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12228178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12228178</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12228178" 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/10.1124/dmd.30.10.1043" target="_blank">Full Text</a>]
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<a id="Chung1997" class="mim-anchor"></a>
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Chung, W.-G., Cha, Y.-N.
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<strong>Oxidation of caffeine to theobromine and theophylline is catalyzed primarily by flavin-containing monooxygenase in liver microsomes.</strong>
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Biochem. Biophys. Res. Commun. 235: 685-688, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207220</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9207220" 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.1997.6866" target="_blank">Full Text</a>]
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<a id="Danks1976" class="mim-anchor"></a>
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Danks, D. M., Hammond, J., Faull, K., Burke, D., Halpern, B.
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<strong>Trimethylaminuria: diet does not always control the fishy odor. (Letter)</strong>
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New Eng. J. Med. 295: 962, 1976.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/987532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">987532</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=987532" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Dolphin1996" class="mim-anchor"></a>
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Dolphin, C. T., Cullingford, T. E., Shephard, E. A., Smith, R. L., Phillips, I. R.
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<strong>Differential developmental and tissue-specific regulation of expression of the genes encoding three members of the flavin-containing monooxygenase family of man, FMO1, FMO3 and FMO4.</strong>
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Europ. J. Biochem. 235: 683-689, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8654418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8654418</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8654418" 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.1432-1033.1996.00683.x" target="_blank">Full Text</a>]
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<a id="Dolphin1997" class="mim-anchor"></a>
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Dolphin, C. T., Janmohamed, A., Smith, R. L., Shephard, E. A., Phillips, I. R.
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<strong>Missense mutation in flavin-containing mono-oxygenase 3 gene, FMO3, underlies fish-odour syndrome.</strong>
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Nature Genet. 17: 491-494, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398858</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398858" 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/ng1297-491" target="_blank">Full Text</a>]
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Dolphin, C. T., Janmohamed, A., Smith, R. L., Shephard, E. A., Phillips, I. R.
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<strong>Compound heterozygosity for missense mutations in the flavin-containing monooxygenase 3 (FMO3) gene in patients with fish-odour syndrome.</strong>
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Pharmacogenetics 10: 799-807, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11191884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11191884</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11191884" 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/10.1097/00008571-200012000-00005" target="_blank">Full Text</a>]
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<strong>Structural organization of the human flavin-containing monooxygenase 3 gene (FMO3), the favored candidate for fish-odor syndrome, determined directly from genomic DNA.</strong>
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[<a href="https://doi.org/10.1006/geno.1997.5031" target="_blank">Full Text</a>]
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<strong>A novel deletion in the flavin-containing monooxygenase gene (FMO3) in a Greek patient with trimethylaminuria.</strong>
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[<a href="https://doi.org/10.1097/00008571-200103000-00007" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.10252" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/taap.1994.1042" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1203/00006450-200202000-00018" target="_blank">Full Text</a>]
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<a id="Krueger2005" class="mim-anchor"></a>
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<strong>Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15922018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15922018</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15922018[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=15922018" 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.pharmthera.2005.01.001" target="_blank">Full Text</a>]
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<a id="Lomri1992" class="mim-anchor"></a>
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<strong>Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1542660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1542660</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1542660" 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/10.1073/pnas.89.5.1685" target="_blank">Full Text</a>]
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<a id="Park1999" class="mim-anchor"></a>
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Park, C.-S., Chung, W.-G., Kang, J.-H., Roh, H.-K., Lee, K.-H., Cha, Y.-N.
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<strong>Phenotyping of flavin-containing monooxygenase using caffeine metabolism and genotyping of FMO3 gene in a Korean population.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10376762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10376762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10376762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Phillips1995" class="mim-anchor"></a>
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Phillips, I. R., Dolphin, C. T., Clair, P., Hadley, M. R., Hutt, A. J., McCombie, R. R., Smith, R. L., Shephard, E. A.
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[<a href="https://doi.org/10.1016/0009-2797(94)03580-2" target="_blank">Full Text</a>]
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Phillips, I. R., Shephard, E. A.
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<strong>Flavin-containing monooxygenases: mutations, disease and drug response.</strong>
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[<a href="https://doi.org/10.1016/j.tips.2008.03.004" target="_blank">Full Text</a>]
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<a id="Shephard1993" class="mim-anchor"></a>
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Shephard, E. A., Dolphin, C. T., Fox, M. F., Povey, S., Smith, R., Phillips, I. R.
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<strong>Localization of genes encoding three distinct flavin-containing monooxygenases to human chromosome 1q.</strong>
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Genomics 16: 85-89, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8486388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8486388</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8486388" 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/geno.1993.1144" target="_blank">Full Text</a>]
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Treacy, E. P., Akerman, B. R., Chow, L. M. L., Youil, R., Bibeau, C., Lin, J., Bruce, A. G., Knight, M., Danks, D. M., Cashman, J. R., Forrest, S. M.
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<strong>Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication.</strong>
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Hum. Molec. Genet. 7: 839-845, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9536088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9536088</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9536088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/7.5.839" target="_blank">Full Text</a>]
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Zhang, J., Tran, Q., Lattard, V., Cashman, J. R.
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<strong>Deleterious mutations in the flavin-containing monooxygenase 3 (FMO3) gene causing trimethylaminuria.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12893987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12893987</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12893987" 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/10.1097/00008571-200308000-00007" target="_blank">Full Text</a>]
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Ziegler, D. M.
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<strong>Flavin-containing monooxygenases: enzymes adapted for multisubstrate specificity.</strong>
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Trends Pharm. Sci. 11: 321-324, 1990.
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[<a href="https://doi.org/10.1016/0165-6147(90)90235-z" target="_blank">Full Text</a>]
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Zschocke, J., Kohlmueller, D., Quak, E., Meissner, T., Hoffmann, G. F., Mayatepek, E.
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<strong>Mild trimethylaminuria caused by common variants in FMO3 gene.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10485731/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10485731</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10485731" 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/s0140-6736(99)80019-1" 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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Joanna S. Amberger - updated : 9/23/2008
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Victor A. McKusick - updated : 11/26/2003<br>Victor A. McKusick - updated : 10/14/2003<br>Victor A. McKusick - updated : 5/18/2001<br>Victor A. McKusick - updated : 3/2/2001<br>Victor A. McKusick - updated : 1/6/2000<br>Victor A. McKusick - updated : 9/30/1999<br>Rebekah S. Rasooly - updated : 6/30/1999<br>Victor A. McKusick - updated : 5/14/1999<br>Victor A. McKusick - updated : 5/22/1998<br>Victor A. McKusick - updated : 2/4/1998<br>Victor A. McKusick - updated : 12/2/1997<br>Victor A. McKusick - updated : 10/24/1997
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<span class="mim-text-font">
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Victor A. McKusick : 5/4/1993
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</span>
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<a id="editHistory" class="mim-anchor"></a>
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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 : 11/07/2022
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carol : 03/26/2017<br>carol : 03/25/2017<br>alopez : 08/12/2015<br>mcolton : 7/30/2015<br>joanna : 6/16/2015<br>terry : 9/7/2012<br>carol : 10/24/2008<br>joanna : 10/22/2008<br>carol : 9/24/2008<br>carol : 9/24/2008<br>joanna : 9/23/2008<br>mgross : 11/20/2006<br>terry : 11/4/2004<br>tkritzer : 12/2/2003<br>terry : 11/26/2003<br>alopez : 10/14/2003<br>mcapotos : 6/1/2001<br>mcapotos : 5/29/2001<br>terry : 5/18/2001<br>carol : 3/12/2001<br>cwells : 3/8/2001<br>terry : 3/2/2001<br>mgross : 1/14/2000<br>terry : 1/6/2000<br>alopez : 11/16/1999<br>alopez : 10/6/1999<br>alopez : 10/6/1999<br>terry : 9/30/1999<br>mgross : 6/30/1999<br>mgross : 6/30/1999<br>mgross : 6/3/1999<br>mgross : 5/28/1999<br>terry : 5/14/1999<br>terry : 6/3/1998<br>terry : 5/22/1998<br>mark : 2/5/1998<br>terry : 2/4/1998<br>jenny : 12/2/1997<br>terry : 11/26/1997<br>terry : 10/29/1997<br>mark : 10/25/1997<br>terry : 10/24/1997<br>carol : 5/4/1993
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<h3>
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<span class="mim-font">
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<strong>*</strong> 136132
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</span>
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</h3>
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<div>
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<h3>
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FLAVIN-CONTAINING DIMETHYLANILINE MONOOXYGENASE 3; FMO3
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</h3>
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<br />
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<div >
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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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FLAVIN-CONTAINING MONOOXYGENASE 3
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</span>
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</h4>
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</div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: FMO3</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 237959005;
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<strong>ICD10CM:</strong> E72.52;
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</p>
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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: 1q24.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:171,090,905-171,117,819 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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1q24.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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Trimethylaminuria
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</td>
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<td>
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<span class="mim-font">
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602079
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</table>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The mammalian flavin-containing monooxygenases (FMO; EC 1.14.13.8) represent a multigene family whose gene products are localized in the endoplasmic reticulum of many tissues. These enzymes catalyze the NADPH-dependent oxidative metabolism of many drugs, pesticides, and other foreign compounds. Their substrates are soft nucleophiles with an electron-rich center, typically a nitrogen, sulfur or phosphorus-containing functional group, as the site for oxidative attack by the enzyme (Ziegler, 1990; Hines et al., 1994). </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>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>Lomri et al. (1992) isolated a full-length cDNA sequence for FMO3, which they designated FMO II, from an adult human liver cDNA library. This cDNA encoded a deduced 533-amino acid protein. </p><p>Dolphin et al. (1996) also isolated an FMO3 cDNA from a human liver library. This cDNA encoded a deduced 532-amino acid protein that shared 84% sequence identity with the rabbit FMO3 protein. </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>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>Dolphin et al. (1997) determined that the FMO3 gene contains 1 noncoding and 8 coding exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By use of PCR with DNAs from somatic cell hybrids, Shephard et al. (1993) mapped the FMO3 gene to chromosome 1. FMO3 is probably located in a cluster with FMO1 (136130) and FMO4 (136131) at 1q23-q25. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using quantitative RNase protection assays, Phillips et al. (1995) and Dolphin et al. (1996) determined that FMO3 is present in low abundance in fetal liver and lung and in adult kidney and lung, and in much greater abundance in adult liver. They determined that FMO3 and FMO1 (136130) are subject to developmental and tissue-specific regulation and, in the liver, there is a developmental switch in the expression of these genes. </p><p>By Western blot analysis of human liver microsomal samples ranging from 8 weeks gestation to 18 years of age, Koukouritaki et al. (2002) confirmed that FMO1 is the major fetal isoform and FMO3 is the major adult isoform. The highest level of FMO1 expression was observed in embryonic samples at 8 to 15 weeks of gestation; its expression was low, but detectable in most samples within the first 3 days of life, but then was extinguished in all but a few samples. In contrast, the onset of FMO3 expression was highly variable, with most individuals failing to express this isoform during the neonatal period. FMO3 was expressed at intermediate levels until 11 years of age when a gender-independent increase in FMO3 expression was observed during puberty. Koukouritaki et al. (2002) observed pronounced interindividual variation of FMO3 protein levels from 2- to 20-fold. </p><p>Phillips and Shephard (2008) noted that the delay between silencing of the FMO1 gene and the full activation of FMO3 means that during the first year of life many children have no, or very little, drug-metabolizing FMOs in their liver. </p><p>Hernandez et al. (2003) pointed out that compromised activity of FMO3 is expected to have implications for the efficacy of drug treatment and the possibility of adverse drug reactions in patients with trimethylaminuria (TMAU; 602079) and in the general population. In addition to metabolizing the dietary-derived amine TMA, FMO3 catalyzes the NADPH-dependent oxidation of numerous foreign compounds, including therapeutic drugs such as the antiestrogen tamoxifen, the antifungal ketoconazole, and the nonsteroidal antiinflammatory drugs sulindac sulfide and benzydamine, as reviewed by Cashman and Zhang (2002). Sufferers of trimethylaminuria may display a reduced ability to metabolize substrates for FMO3 such as nicotine (Ayesh et al., 1988). </p><p>FMO3 metabolizes a number of drugs, including amphetamine, clozapine, deprenyl, metamphetamine, tamoxifen, ethionamide, thiacetazone, and sulindac sulfide (see reviews by Krueger and Williams (2005) and Phillips and Shephard (2008)). </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>Akerman et al. (1997) and Treacy et al. (1998) reported 3 different mutations in the FMO3 gene in Australian probands with trimethylaminuria (602079), or fish-odor syndrome, who shared a particular polymorphic haplotype. Treacy et al. (1998) showed that these mutations impair N-oxygenation of xenobiotics and are responsible for the trimethylaminuria phenotype. A nonsense mutation, glu305 to ter (E305X; 136132.0001), was found on 6 mutant chromosomes of British origin, homozygous in 1 and heterozygous in 4 individuals. Homozygosity for a missense mutation, val257 to met (V257M; 136132.0002), was found in 1 individual of Greek origin. Heterozygosity for a met66-to-ile (M66I; 136132.0003) mutation was found in 1 individual of Irish extraction. </p><p>In a patient with trimethylaminuria, Dolphin et al. (1997) found a pro153-to-leu mutation in the FMO3 gene (P153L; 136132.0004) that abolished FMO3 catalytic activity. They demonstrated that FMO3 with the 551C-T mutation could not support the metabolism of dietary-derived trimethylamine (TMA). In addition to TMA, FMOs catalyze the oxidation of a range of structurally diverse compounds, including drugs, pesticides, and other xenobiotics. The authors commented that although patients with trimethylaminuria are apparently deficient in nicotine N-oxidation, a reaction catalyzed predominantly by FMO3, the pharmacologic and toxicologic significance of an inherited block in FMO3-mediated oxidative metabolism is unclear. </p><p>Treacy et al. (1998) found that nonsense and missense mutations in the FMO3 gene were associated with a severe trimethylaminuria phenotype and were also implicated in impaired metabolism of other nitrogen- and sulfur-containing substances, including biogenic amines, both clinically and when mutated proteins expressed from cDNA were studied in vitro. The findings illustrated the clinical role played by human FMO3 in the metabolism of xenobiotic substrates and endogenous amines. One patient of English-Irish extraction with severe hypertension was observed with blood pressure of 200/110 following the use of nasal epinephrine. Adverse tyramine reactions were observed in at least 3 patients. Urticaria and intolerance of sulfur-containing medication was observed in a patient homozygous for the P153L mutation. </p><p>Chung and Cha (1997) showed that production of theobromine from caffeine is catalyzed primarily by the FMO present in adult human liver microsomes. They determined FMO activity in vivo noninvasively by taking the urinary molar concentration ratio of theobromine/caffeine in a Korean population. In 82 Korean volunteers, Park et al. (1999) determined FMO activity by taking the molar concentration ratio of theobromine and caffeine present in the 1-hour urine (between 4 and 5 hours) samples collected after administration of a cup of coffee containing 110 mg of caffeine. Among 82 volunteers, there were 19 women and 63 men (30 smokers and 52 nonsmokers). Volunteers were divided into 2 groups comprising low (0.53-2.99) and high (3.18-11.95) FMO activities separated by an antimode of 3.18. Genomic DNAs from peripheral blood were amplified by PCR with oligonucleotides designed from intronic sequences of the human FMO3 gene. Comparing nucleotide sequences of the amplified FMO3 gene originating from randomly selected individuals with low and high FMO activities, 9 point mutations were identified in the open reading frame sequences. </p><p>Akerman et al. (1999) studied a cohort of North American individuals with severe trimethylaminuria, defined by a reduction of TMA oxidation below 50% of normal. They detected 4 novel FOM3 mutations, including 2 missense mutations, ala52 to thr (A52T; 136132.0008) and arg387 to leu (R387L; 136132.0007), and 1 nonsense mutation, glu314 to ter (E314X; 136132.0009). The fourth allele was apparently composed of 2 relatively common polymorphisms (lys158-gly308) found in the general population. For the E314X mutation, loss of activity was strongly predicted due to truncation of the FMO3 protein at codon 314, since deletion of even the final 30 amino acids of this 532-residue protein will ablate function in vitro. While the A52T and R387L mutations had not been expressed, they satisfied several conditions for designation as disease-causing: the changes were not observed in controls, they were nonconservative substitutions, and no other changes were identified in the probands when sequencing all expressed FMO3 exons. Furthermore, the A52T and R387L residues appear to be highly conserved within the FMO gene family. The authors suggested that the 2 common changes (lys158-gly308) in cis diminished the activity of the enzyme and rendered it incapable of compensating for the A52T mutation carried by the other allele. </p><p>Hernandez et al. (2003) described a human FMO3 mutation database. They indicated that 16 mutations (12 missense, 3 nonsense, and 1 gross deletion) were known to cause trimethylaminuria. </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>15 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 TRIMETHYLAMINURIA</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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FMO3, GLU305TER
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<br />
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SNP: rs61753344,
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gnomAD: rs61753344,
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ClinVar: RCV000017697, RCV001036315
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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>Akerman et al. (1997) identified a glu305-to-ter (E305X) mutation in the FMO3 gene in 6 mutant chromosomes from Australian probands of British origin with trimethylaminuria (TMAU; 602079). The mutation was homozygous in 1 and heterozygous in 4 individuals. The E305X homozygote had, in addition to trimethylaminuria, tachycardia and severe hypertension after eating cheese (which contains tyramine) and after using nasal epinephrine in the treatment of an epistaxis (Danks et al., 1976). The FMO3 enzyme metabolizes tyramine. Mutant FMO3 cDNA for this mutation demonstrated loss of substrate activity for TMA and tyramine when expressed in E. coli. </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 TRIMETHYLAMINURIA</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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FMO3, VAL257MET
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<br />
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SNP: rs1736557,
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gnomAD: rs1736557,
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ClinVar: RCV000017698, RCV000253910, RCV003669101
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an Australian individual of Greek origin with trimethylaminuria (TMAU; 602079), Akerman et al. (1997) found homozygosity for a val257-to-met (V257M) missense mutation in the FMO3 gene.</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 TRIMETHYLAMINURIA</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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FMO3, MET66ILE
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|
|
|
|
<br />
|
|
|
|
SNP: rs72549323,
|
|
|
|
|
|
gnomAD: rs72549323,
|
|
|
|
|
|
ClinVar: RCV000017699
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Australian individual of Irish origin with trimethylaminuria (TMAU; 602079), Akerman et al. (1997) found a met66-to-ile (M66I) mutation in the FMO3 gene in heterozygous state. Mutant FMO3 cDNA containing the M66I substitution demonstrated loss of substrate activity for TMA and tyramine when expressed in E. coli.</p><p>In an Australian patient with trimethylaminuria, Akerman et al. (1999) found compound heterozygosity for 2 missense mutations in the FMO3 gene: M66I and arg492 to trp (R492W; 136132.0005). The second of these mutations involved a hypermutable CpG site and was a nonconservative change in a highly conserved region of the FMO3 gene. Arg492 was conserved in all FMO isoforms. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 TRIMETHYLAMINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
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|
|
|
FMO3, PRO153LEU
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|
|
|
<br />
|
|
|
|
SNP: rs72549326,
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|
|
|
|
|
gnomAD: rs72549326,
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|
|
|
|
|
ClinVar: RCV000017701, RCV002223760, RCV004755741
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a brother and sister with trimethylaminuria (TMAU; 602079), Dolphin et al. (1997) identified a homozygous 551C-T transition in the FMO3 gene, changing a CCC proline triplet at codon 153 to a CTC leucine triplet (P153L). Their unaffected parents and a third sib were heterozygous for the mutation. The authors found the same mutation in 2 other trimethylaminuria kindreds, in which it also cosegregated with the disorder. In the first kindred studied, the leu153 allele was found to carry a polymorphism at codon 158, namely glu158. Among 30 unrelated, non-trimethylaminuric individuals, pro153 was found in all, whereas glu158 and lys158 occurred in frequencies of approximately 50% each. </p>
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 TRIMETHYLAMINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
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|
|
|
FMO3, ARG492TRP
|
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|
|
<br />
|
|
|
|
SNP: rs72549334,
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|
|
|
|
|
gnomAD: rs72549334,
|
|
|
|
|
|
ClinVar: RCV000017702, RCV003574701
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg492-to-trp (R492W) mutation in the FMO3 gene that was found in compound heterozygous state in a patient with trimethylaminuria (TMAU; 602079) by Akerman et al. (1999), see 136132.0003. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 FMO3 ACTIVITY, DECREASED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FMO3, GLY148TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs72549325,
|
|
|
|
|
|
gnomAD: rs72549325,
|
|
|
|
|
|
ClinVar: RCV000017703, RCV003556036
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Park et al. (1999) determined FMO activity by taking the molar concentration ratio of theobromine and caffeine present in the 1-hour urine (between 4 and 5 hours) samples collected after administration of a cup of coffee containing 110 mg of caffeine. In an individual who had the second lowest FMO activity, they detected a missense mutation, 442G-T in exon 4, that yielded a premature TGA stop codon replacing glycine-148 (G148X). He had the mutation in heterozygous state. His mother also had the heterozygous stop codon and equally low FMO activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 TRIMETHYLAMINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FMO3, ARG387LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs72549331,
|
|
|
|
|
|
gnomAD: rs72549331,
|
|
|
|
|
|
ClinVar: RCV000017704, RCV003398530
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Metis patient from Canada with trimethylaminuria (TMAU; 602079), Akerman et al. (1999) found homozygosity for a G-to-T transversion at nucleotide 1160 of the FMO3 gene, resulting in an arg387-to-leu (R387L) mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 TRIMETHYLAMINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FMO3, ALA52THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs72549321,
|
|
|
|
|
|
gnomAD: rs72549321,
|
|
|
|
|
|
ClinVar: RCV000017700, RCV004700244
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a North American patient with trimethylaminuria (TMAU; 602079), Akerman et al. (1999) identified a G-to-A transition at nucleotide 154 of the FMO3 gene, resulting in an ala52-to-thr (A52T) mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 TRIMETHYLAMINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FMO3, GLU314TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs72549330,
|
|
|
|
|
|
gnomAD: rs72549330,
|
|
|
|
|
|
ClinVar: RCV000017705
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a North American patient with trimethylaminuria (TMAU; 602079), Akerman et al. (1999) identified a G-to-T transversion at nucleotide 940 of the FMO3 gene, resulting in a glu314-to-ter (E314X) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 TRIMETHYLAMINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FMO3, ASN61SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs72549322,
|
|
|
|
|
|
gnomAD: rs72549322,
|
|
|
|
|
|
ClinVar: RCV000017706
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Dolphin et al. (2000) found 2 individuals with trimethylaminuria (TMAU; 602079) who were compound heterozygous for the P153L missense mutation (136132.0004) and a novel asn61-to-ser (N61S) mutation in the FMO3 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 TRIMETHYLAMINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FMO3, MET434ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs72549332,
|
|
|
|
|
|
gnomAD: rs72549332,
|
|
|
|
|
|
ClinVar: RCV000017707, RCV003556037
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Dolphin et al. (2000) found that a patient with trimethylaminuria (602079) was compound heterozygous for the R492W mutation (136132.0005) and a novel met434-to-ile (M434I) mutation in the FMO3 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 TRIMETHYLAMINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FMO3, 2-EX DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000017708
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Forrest et al. (2001) described trimethylaminuria (TMAU; 602079) caused by a deletion of more than 12 kb in the FMO3 gene in a 15-year-old Australian male of Greek parents. The deletion began 328 bp upstream from exon 1; the 3-prime end of the deletion occurred in intron 2. The deletion was 12,226 bp long. Because of homozygosity for the FMO3 gene deletion, it was predicted that in addition to loss of monooxygenase function for human FMO3 substrates, such as trimethylamine and other amines, the proband would exhibit decreased tolerance of biogenic amines, both medicinal and dietary. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 TRIMETHYLAMINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FMO3, GLU32LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs72549320,
|
|
|
|
|
|
|
|
ClinVar: RCV000017709
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with trimethylaminuria (TMAU; 602079), Zhang et al. (2003) identified a glu32-to-lys (E32K) mutation in the FMO3 gene. Expression studies showed that the E32K mutation abrogated the catalytic activity of the enzyme. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 TRIMETHYLAMINURIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FMO3, 1-BP DEL, 191A
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000017710
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an individual with trimethylaminuria (TMAU; 602079), Zhang et al. (2003) identified compound heterozygosity for 2 mutations in the FMO3 gene: a P153L change (136132.0004) and a 1-bp deletion (191delA) in exon 3 at codon 64. The deletion resulted in a frameshift and premature termination of the gene immediately after codon 65. Family pedigree analysis revealed that the 2 mutations were carried on different alleles in this individual. Both mutations abolished the catalytic activity of the enzyme, explaining the severe clinical expression of trimethylaminuria. The patient was examined at the age of 3 years, at which time he was found to have 61% unmetabolized trimethylamine in urine, compatible with severe trimethylaminuria. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 TRIMETHYLAMINURIA, MILD</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FMO3, GLU308GLY AND GLU158LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2266780, rs2266782,
|
|
|
|
|
|
gnomAD: rs2266780, rs2266782,
|
|
|
|
|
|
ClinVar: RCV000017711, RCV000201276, RCV000201278, RCV000248637, RCV000254132, RCV000290538, RCV000361492, RCV001642531, RCV001668146, RCV002251938
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with mild trimethylaminuria (TMAU; 602079), Zschocke et al. (1999) identified compound heterozygosity for mutations in the FMO3 gene: a P151L substitution (136132.0004) on one allele, and 2 common polymorphisms, glu308 to gly (E308G) and glu 158 to lys (E158K), on the other. Zschocke et al. (1999) noted that homozygosity for the P151L mutation had been found to cause severe trimethylaminuria. They found that individuals homozygous for the variant allele with the 2 common polymorphisms had decreased TMA oxidation capacity (less than 50%) indicative of mild trimethylaminuria. </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">
|
|
Akerman, B. R., Chow, L., Forrest, S., Youil, R., Cashman, J., Treacy, E. P.
|
|
<strong>Mutations in the flavin-containing monoxygenase (sic) form 3 (FMO3) gene cause trimethylaminuria, fish odour syndrome. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 61 (suppl.): A53 only, 1997.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Akerman, B. R., Forrest, S., Chow, L., Youil, R., Knight, M., Treacy, E. P.
|
|
<strong>Two novel mutations of the FMO3 gene in a proband with trimethylaminuria.</strong>
|
|
Hum. Mutat. 13: 376-379, 1999.
|
|
|
|
|
|
[PubMed: 10338091]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)13:5<376::AID-HUMU5>3.0.CO;2-A]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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