4010 lines
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Entry
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- *604653 - SOLUTE CARRIER FAMILY 40 (IRON-REGULATED TRANSPORTER), MEMBER 1; SLC40A1
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- OMIM
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<p>
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<span class="h4">*604653</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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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604653">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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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000138449;t=ENST00000261024" 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=30061" 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=604653" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000138449;t=ENST00000261024" 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_014585,XM_047444066" 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_014585" 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=604653" 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=05229&isoform_id=05229_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/SLC40A1" 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/7023678,7109249,7264729,7657100,8895485,12053383,22902430,23273532,33337962,38043880,38601958,38601960,40204823,48428687,49065554,57976028,62702155,62898033,67633296,67633298,67633300,67633302,67633304,67633306,119631306,119631307,158257724,189054570,297045077,1042780677,1042780679,1042780681,1042780683,1042780685,1042780687,1042780689,1042780691,1042780693,1042780695,1042780697,1042780699,1042780701,1042780703,1042780705,1042780707,1042780709,1042780711,1042780713,1042780715,1042780717,1042780719,1042780721,1042780723,1042780725,1042780727,1042780729,1042780731,1042780733,1042780735,1042780737,1042780739,1042780741,1042780743,1042780745,1042780747,2217327320,2462572348,2601172232" 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/Q9NP59" 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=30061" 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=ENSG00000138449;t=ENST00000261024" 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=SLC40A1" 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=SLC40A1" 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+30061" 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/SLC40A1" 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:30061" 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/30061" 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=chr2&hgg_gene=ENST00000261024.7&hgg_start=189560590&hgg_end=189580786&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://medlineplus.gov/genetics/gene/slc40a1" 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=604653[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=604653[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/SLC40A1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000138449" 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=SLC40A1" 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=SLC40A1" 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=SLC40A1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SLC40A1&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/PA35805" 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:10909" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1315204" 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/SLC40A1#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:1315204" 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/30061/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=30061" 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=WBGene00019977;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00019977 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00021354;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00021354 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-000511-8" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:30061" 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=SLC40A1&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> 1303911001, 719975002<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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604653
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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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SOLUTE CARRIER FAMILY 40 (IRON-REGULATED TRANSPORTER), MEMBER 1; SLC40A1
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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FERROPORTIN 1; FPN1<br />
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IRON-REGULATED TRANSPORTER 1; IREG1<br />
|
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SOLUTE CARRIER FAMILY 11 (PROTON-COUPLED DIVALENT METAL ION TRANSPORTER), MEMBER 3, FORMERLY; SLC11A3, FORMERLY
|
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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=SLC40A1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SLC40A1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/2/857?start=-3&limit=10&highlight=857">2q32.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:189560590-189580786&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'})">2:189,560,590-189,580,786</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<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>
|
|
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|
<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/857?start=-3&limit=10&highlight=857">
|
|
2q32.2
|
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</a>
|
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</span>
|
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</td>
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|
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<td>
|
|
<span class="mim-font">
|
|
Hemochromatosis, type 4
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/606069"> 606069 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/604653" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/604653" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
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<p>Defects in iron absorption and utilization lead to iron deficiency and overload disorders. Adult mammals absorb iron through the duodenum, whereas embryos obtain iron through placental transport. Iron uptake from the intestinal lumen through the apical surface of the polarized duodenal enterocytes is mediated by the divalent metal transporter, DMT1 (<a href="/entry/600523">600523</a>). A second transporter had been postulated to export iron across the basolateral surface to the circulation. <a href="#6" class="mim-tip-reference" title="Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, Z., Law, T. C., Brugnara, C., Lux, S. E., Pinkus, G. S., Pinkus, J. L., Kingsley, P. D., Palis, J., Fleming, M. D., Andrews, N. C., Zon, L. I. <strong>Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter.</strong> Nature 403: 776-781, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10693807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10693807</a>] [<a href="https://doi.org/10.1038/35001596" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10693807">Donovan et al. (2000)</a> used positional cloning to identify the gene responsible for the hypochromic anemia of the zebrafish mutant 'weissherbst.' The gene, which they called ferroportin-1 (fpn1), encodes a multiple-transmembrane domain protein expressed in the yolk sac that was a candidate for the elusive iron transporter. Zebrafish ferroportin-1 is required for the transport of iron from maternally-derived yolk stores to the circulation and functions as an iron exporter when expressed in Xenopus oocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10693807" 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="Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, Z., Law, T. C., Brugnara, C., Lux, S. E., Pinkus, G. S., Pinkus, J. L., Kingsley, P. D., Palis, J., Fleming, M. D., Andrews, N. C., Zon, L. I. <strong>Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter.</strong> Nature 403: 776-781, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10693807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10693807</a>] [<a href="https://doi.org/10.1038/35001596" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10693807">Donovan et al. (2000)</a> isolated mouse and human ferroportin-1 cDNAs by RT-PCR of liver and placenta, respectively. Human ferroportin-1 is a protein of 571 amino acids. A conserved sequence, predicted to form a hairpin-loop structure typical of iron response elements (IREs), was identified in the 5-prime untranslated region of the cDNAs from all 3 species. Northern blot analysis showed the highest level of expression in human placenta, liver, spleen, and kidney. In mouse, primitive erythroblasts derived from the blood islands do not express ferroportin-1, whereas the trophoblast cells of the inner placenta express high levels of ferroportin-1. In the human placenta, ferroportin-1 protein was primarily expressed in a basal location within the syncytiotrophoblasts, suggesting that it transports iron from mother to embryo. Mammalian ferroportin-1 is also expressed at the basolateral surface of duodenal enterocytes. On the basis of basolateral expression pattern of ferroportin-1 in mammalian enterocytes and the implication that ferroportin-1 is required for intestinal iron absorption and iron transport in zebrafish, <a href="#6" class="mim-tip-reference" title="Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, Z., Law, T. C., Brugnara, C., Lux, S. E., Pinkus, G. S., Pinkus, J. L., Kingsley, P. D., Palis, J., Fleming, M. D., Andrews, N. C., Zon, L. I. <strong>Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter.</strong> Nature 403: 776-781, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10693807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10693807</a>] [<a href="https://doi.org/10.1038/35001596" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10693807">Donovan et al. (2000)</a> suggested that the protein is probably involved in iron export from enterocytes in mammals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10693807" 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>Iron absorption by the duodenal mucosa is initiated by uptake of ferrous Fe(II) iron across the brush border membrane and culminates in transfer of the metal across the basolateral membrane to the portal vein circulation by an unknown mechanism. Using a subtractive cloning strategy and PCR analysis, <a href="#11" class="mim-tip-reference" title="McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., Hediger, M. A., Hentze, M. W., Simpson, R. J. <strong>A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.</strong> Molec. Cell 5: 299-309, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10882071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10882071</a>] [<a href="https://doi.org/10.1016/s1097-2765(00)80425-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10882071">McKie et al. (2000)</a> isolated mouse and human duodenal cDNAs encoding FPN1, which they called iron-regulated transporter-1 (IREG1). The IREG1 protein contains 10 transmembrane domains and is localized to the basolateral membrane of polarized epithelial cells. IREG1 mRNA and protein expression are increased under conditions of increased iron absorption, and the 5-prime untranslated region of the IREG1 mRNA contains a functional IRE. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10882071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By FISH, <a href="#9" class="mim-tip-reference" title="Haile, D. J. <strong>Assignment of Slc11a3 to mouse chromosome 1 band 1B and SLC11A3 to human chromosome 2q21 by in situ hybridization.</strong> Cytogenet. Cell Genet. 88: 328-329, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10828623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10828623</a>] [<a href="https://doi.org/10.1159/000015522" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10828623">Haile (2000)</a> mapped the SLC40A1 gene to human chromosome 2q32 and mouse chromosome 1B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10828623" 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="McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., Hediger, M. A., Hentze, M. W., Simpson, R. J. <strong>A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.</strong> Molec. Cell 5: 299-309, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10882071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10882071</a>] [<a href="https://doi.org/10.1016/s1097-2765(00)80425-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10882071">McKie et al. (2000)</a> found that IREG1 stimulated iron efflux following expression in Xenopus oocytes. They concluded that IREG1 represents the long-sought duodenal iron export protein and is upregulated in the iron overload disease hereditary hemochromatosis (<a href="/entry/235200">235200</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10882071" 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="#14" class="mim-tip-reference" title="Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., Kaplan, J. <strong>Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.</strong> Science 306: 2090-2093, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15514116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15514116</a>] [<a href="https://doi.org/10.1126/science.1104742" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15514116">Nemeth et al. (2004)</a> reported that hepcidin (<a href="/entry/606464">606464</a>) bound to ferroportin in tissue culture cells. After binding, ferroportin was internalized and degraded, leading to decreased export of cellular iron. <a href="#14" class="mim-tip-reference" title="Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., Kaplan, J. <strong>Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.</strong> Science 306: 2090-2093, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15514116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15514116</a>] [<a href="https://doi.org/10.1126/science.1104742" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15514116">Nemeth et al. (2004)</a> postulated that the posttranslational regulation of ferroportin by hepcidin may complete a homeostatic loop regulating iron plasma levels and the tissue distribution of iron. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15514116" 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="#18" class="mim-tip-reference" title="Sangokoya, C., Doss, J. F., Chi, J.-T. <strong>Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin.</strong> PLoS Genet. 9: e1003408, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23593016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23593016</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23593016[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/10.1371/journal.pgen.1003408" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23593016">Sangokoya et al. (2013)</a> stated that FPN expression is downregulated in an iron-dependent manner by binding of iron regulatory protein (IRP; see <a href="/entry/100880">100880</a>) to the IRE in the 5-prime UTR of the FPN transcript. Using a reporter gene assay, they confirmed that FPN expression decreased during iron depletion and increased significantly during iron supplementation in human HepG2 hepatocytes. <a href="#18" class="mim-tip-reference" title="Sangokoya, C., Doss, J. F., Chi, J.-T. <strong>Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin.</strong> PLoS Genet. 9: e1003408, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23593016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23593016</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23593016[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/10.1371/journal.pgen.1003408" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23593016">Sangokoya et al. (2013)</a> also identified a regulatory region in the 3-prime UTR of FPN that bound the microRNA MIR485-3p (<a href="/entry/615385">615385</a>). MIR485-3p was induced during iron deficiency in human cell lines, and MIR485-3p binding to the 3-prime UTR of the FPN transcript repressed FPN translation, leading to increased cellular ferritin (see <a href="/entry/134790">134790</a>) levels and increased cellular iron. Inhibition of MIR485-3p activity or mutation of the MIR485-3p-binding site in the FPN 3-prime UTR relieved FPN repression and led to cellular iron deficiency. IRP and MIR485-3p downregulated FPN expression in an additive manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23593016" 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="Nairz, M., Schleicher, U., Schroll, A., Sonnweber, T., Theurl, I., Ludwiczek, S., Talasz, H., Brandacher, G., Moser, P. L., Muckenthaler, M. U., Fang, F. C., Bogdan, C., Weiss, G. <strong>Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection.</strong> J. Exp. Med. 210: 855-873, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23630227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23630227</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23630227[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20121946" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23630227">Nairz et al. (2013)</a> found that macrophages from mice lacking nitric oxide synthase-2 (NOS2; <a href="/entry/163730">163730</a>) displayed reduced expression of Fpn1. Nitric oxide upregulated FPN1 expression in mouse and human cells. Nos2-null mouse macrophages had increased iron content due to reduced Fpn1 activity. Reduced Fpn1 expression allowed enhanced iron acquisition by the intracellular bacterium Salmonella typhimurium. Mice lacking Nos2 or mice in which Nos2 activity was inhibited had increased iron accumulation in spleen and spleen macrophages. Lack of nitric oxide formation resulted in impaired Nrf2 (NFE2L2; <a href="/entry/600492">600492</a>) expression and, consequently, reduced Fpn1 transcription and cellular iron export. Infection of Nos2-null mice or macrophages with S. typhimurium led not only to increased iron accumulation, but also to reduced Tnf (<a href="/entry/191160">191160</a>), Il2 (<a href="/entry/147680">147680</a>), and Ifng (<a href="/entry/147570">147570</a>) expression and impaired pathogen control, all of which could be restored by treatment with iron chelators or overexpression of Fpn1 or Nrf2. <a href="#13" class="mim-tip-reference" title="Nairz, M., Schleicher, U., Schroll, A., Sonnweber, T., Theurl, I., Ludwiczek, S., Talasz, H., Brandacher, G., Moser, P. L., Muckenthaler, M. U., Fang, F. C., Bogdan, C., Weiss, G. <strong>Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection.</strong> J. Exp. Med. 210: 855-873, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23630227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23630227</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23630227[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20121946" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23630227">Nairz et al. (2013)</a> concluded that iron accumulation in Nos2-null macrophages counteracts a proinflammatory host response and that the protective effects of nitric oxide partially result from its ability to prevent iron overload in macrophages. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23630227" 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="#21" class="mim-tip-reference" title="Zhang, D.-L., Wu, J., Shah, B. N., Greutelaers, K. C., Ghosh, M. C., Ollivierre, H., Su, X., Thuma, P. E., Bedu-Addo, G., Mockenhaupt, F. P., Gordeuk, V. R., Rouault, T. A. <strong>Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk.</strong> Science 359: 1520-1523, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29599243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29599243</a>] [<a href="https://doi.org/10.1126/science.aal2022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29599243">Zhang et al. (2018)</a> found that ferroportin is highly abundant in mature red blood cells and that its activity is inhibited by iron supplementation and hepcidin. Additional deletion of the FPN1 gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. Fpn knockout increased non-heme iron content and intracellular ferritin levels in erythroblasts and resulted in a mild compensated anemia and extramedullary erythropoiesis. The anemia was not caused by a defect in erythroblast differentiation, but instead by the increased fragility and hemolysis of mature red blood cells, as evidenced by the 2.5-fold increase of free plasma hemoglobin after storage at 4 degrees C for 20 hours. <a href="#21" class="mim-tip-reference" title="Zhang, D.-L., Wu, J., Shah, B. N., Greutelaers, K. C., Ghosh, M. C., Ollivierre, H., Su, X., Thuma, P. E., Bedu-Addo, G., Mockenhaupt, F. P., Gordeuk, V. R., Rouault, T. A. <strong>Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk.</strong> Science 359: 1520-1523, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29599243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29599243</a>] [<a href="https://doi.org/10.1126/science.aal2022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29599243">Zhang et al. (2018)</a> intravenously injected wildtype and Fpn knockout mice with Plasmodium yoelii, a lethal murine malaria strain. The knockout mice had 60% more parasite-infected red blood cells than wildtype mice on multiple successive days after infection, and died more rapidly after infection. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29599243" 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 mutation analysis of all exons, intron-exon boundaries, and the 5-prime and 3-prime untranslated region (including the IRE) of the SLC40A1 gene in a Dutch family with hemochromatosis type 4 (HFE4; <a href="/entry/606069">606069</a>), <a href="#15" class="mim-tip-reference" title="Njajou, O. T., Vaessen, N., Joosse, M., Berghuis, B., van Dongen, J. W. F., Breuning, M. H., Snijders, P. J. L. M., Rutten, W. P. F., Sandkuijl, L. A., Oostra, B. A., van Duijn, C. M., Heutink, P. <strong>A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis.</strong> Nature Genet. 28: 213-214, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431687</a>] [<a href="https://doi.org/10.1038/90038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11431687">Njajou et al. (2001)</a> identified a heterozygous A-to-C transversion at nucleotide 734 in exon 5 in all affected individuals. The mutation resulted in an asn144-to-his substitution (<a href="#0001">604653.0001</a>). The substituted asn is a highly conserved amino acid in vertebrates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11431687" 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>Independently, in an Italian family with autosomal dominant hemochromatosis originally reported by <a href="#16" class="mim-tip-reference" title="Pietrangelo, A., Montosi, G., Totaro, A., Garuti, C., Conte, D., Cassanelli, S., Fraquelli, M., Sardini, C., Vasta, F., Gasparini, P. <strong>Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene.</strong> New Eng. J. Med. 341: 725-732, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471458</a>] [<a href="https://doi.org/10.1056/NEJM199909023411003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10471458">Pietrangelo et al. (1999)</a>, <a href="#12" class="mim-tip-reference" title="Montosi, G., Donovan, A., Totaro, A., Garuti, C., Pignatti, E., Cassanelli, S., Trenor, C. C., Gasparini, P., Andrews, N. C., Pietrangelo, A. <strong>Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene.</strong> J. Clin. Invest. 108: 619-623, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11518736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11518736</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11518736[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI13468" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11518736">Montosi et al. (2001)</a> mapped the disease locus responsible for autosomal dominant hemochromatosis to 2q32 and recognized ferroportin as a compelling positional candidate for the site of the mutation. They identified a mutation in the SLC40A1 gene (<a href="#0002">604653.0002</a>). They pointed out that the distinguishing features of this disorder, in addition to autosomal dominant inheritance, is early iron accumulation in reticuloendothelial cells and a marked increase in serum ferritin before elevation of the transferrin saturation. <a href="#8" class="mim-tip-reference" title="Fleming, R. E., Sly, W. S. <strong>Ferroportin mutation in autosomal dominant hemochromatosis: loss of function, gain in understanding.</strong> J. Clin. Invest. 108: 521-522, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11518724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11518724</a>] [<a href="https://doi.org/10.1172/JCI13739" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11518724">Fleming and Sly (2001)</a> commented that haploinsufficiency for ferroportin would (at least initially) favor low serum iron by decreasing dietary iron absorption and by impairing iron release from macrophages. This could explain the low transferrin saturations, the anemia early in life, and the sensitivity to phlebotomy observed in many of these patients. The hepatocellular iron loading might be explained by the secondary effects of the 'erythropoietic regulator' stimulating intestinal iron absorption, or possibly by ferroportin-1 haploinsufficiency in hepatocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10471458+11518724+11518736" 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>Unexplained hyperferritinemia is a common clinical finding, even in asymptomatic persons. When early-onset bilateral cataracts are also present, hereditary hyperferritinemia-cataract syndrome (<a href="/entry/600886">600886</a>), resulting from a heterozygous point mutation in the L ferritin (FTL; <a href="/entry/134790">134790</a>) IRE sequence, can be suspected. <a href="#10" class="mim-tip-reference" title="Hetet, G., Devaux, I., Soufir, N., Grandchamp, B., Beaumont, C. <strong>Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations.</strong> Blood 102: 1904-1910, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12730114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12730114</a>] [<a href="https://doi.org/10.1182/blood-2003-02-0439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12730114">Hetet et al. (2003)</a> sequenced exon 1 of the FTL gene in 52 DNA samples from patients referred for molecular diagnosis of hyperferritinemia-cataract syndrome. They identified 24 samples with a point mutation or deletion in the IRE. For the 28 samples in which no IRE mutation was present, they also genotyped for mutations in the HFE gene (<a href="/entry/613609">613609</a>) and sequenced both the H ferritin (FTH1; <a href="/entry/134770">134770</a>) and SLC40A1 genes. They found an increased frequency (12 of 28) of heterozygotes for the HFE his63-to-asp mutation (H63D; <a href="/entry/613609#0002">613609.0002</a>), but no H ferritin mutations. They identified 3 novel SLC40A1 mutations (<a href="#0004">604653.0004</a>-<a href="#0006">604653.0006</a>), suggesting that these patients had dominant type 4 hemochromatosis. The study demonstrated that both L ferritin IRE and SLC40A1 mutations can account for isolated hyperferritinemia. The presence of cataract does not permit the unambiguous identification of patients with hereditary hyperferritinemia-cataract syndrome, although the existence of a family history of cataract was only encountered in these patients. This raised the possibility that lens ferritin accumulation may be a factor contributing to age-related cataract in the general population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12730114" 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 transfection experiments using HEK 293T cells, <a href="#4" class="mim-tip-reference" title="De Domenico, I., Ward, D. M., Nemeth, E., Vaughn, M. B., Musci, G., Ganz, T., Kaplan, J. <strong>The molecular basis of ferroportin-linked hemochromatosis.</strong> Proc. Nat. Acad. Sci. 102: 8955-8960, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15956209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15956209</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15956209[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0503804102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15956209">De Domenico et al. (2005)</a> showed that known human mutations introduced into the mouse Slc40a1 gene generate proteins that either are defective in cell surface localization or have a decreased ability to be internalized and degraded in response to hepcidin. Coimmunoprecipitation studies revealed that ferroportin is multimeric. Both wildtype and mutant ferroportin participated in the multimer, and mutant ferroportin affected the localization of wildtype ferroportin, its stability, and its response to hepcidin. <a href="#4" class="mim-tip-reference" title="De Domenico, I., Ward, D. M., Nemeth, E., Vaughn, M. B., Musci, G., Ganz, T., Kaplan, J. <strong>The molecular basis of ferroportin-linked hemochromatosis.</strong> Proc. Nat. Acad. Sci. 102: 8955-8960, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15956209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15956209</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15956209[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0503804102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15956209">De Domenico et al. (2005)</a> concluded that the behavior of mutant ferroportin in cell culture and its ability to act as a dominant negative explain the dominant inheritance of the disease as well as the different patient phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15956209" 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="Cremonesi, L., Forni, G. L., Soriani, N., Lamagna, M., Fermo, I., Daraio, F., Galli, A., Pietra, D., Malcovati, L., Ferrari, M., Camaschella, C., Cazzola, M. <strong>Genetic and clinical heterogeneity of ferroportin disease.</strong> Brit. J. Haemat. 131: 663-670, 2005. Note: Erratum: Brit. J. Haemat. 132: 806 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16351644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16351644</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2005.05815.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16351644">Cremonesi et al. (2005)</a> studied 2 Italian families and 1 of Chinese descent with elevated serum ferritin levels and identified heterozygosity for 3 different mutations in the SLC40A1 gene, respectively. The authors noted the variability in phenotypes between the families and suggested that the mutation (<a href="#0007">604653.0007</a>) in the first Italian family, in which the proband had a liver biopsy showing heavy iron deposition in both hepatocytes and Kupffer cells, likely caused decreased responsiveness to hepcidin, whereas the mutations (<a href="#0008">604653.0008</a> and <a href="#0009">604653.0009</a>) in the latter 2 families likely caused defective localization of the protein to the cell surface. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16351644" 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="Wallace, D. F., Subramaniam, V. N. <strong>The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data.</strong> Genet. Med. 18: 618-626, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26633544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26633544</a>] [<a href="https://doi.org/10.1038/gim.2015.140" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26633544">Wallace and Subramaniam (2016)</a> reviewed 161 variants previously associated with any form of hereditary hemochromatosis and found that 43 were represented among next-generation sequence public databases including ESP, 1000 Genomes Project, and ExAC. The frequency of the C282Y mutation in HFE (<a href="/entry/613609#0001">613609.0001</a>) matched previous estimates from similar populations. Of the non-HFE forms of iron overload, TFR2 (<a href="/entry/604720">604720</a>)-, HFE2 (<a href="/entry/608374">608374</a>)-, and HAMP (<a href="/entry/606464">606464</a>)-related forms were extremely rare, with pathogenic allele frequencies in the range of 0.00007 to 0.0005. However, SLC40A1 variants were identified in several populations (pathogenic allele frequency 0.0004), being most prevalent among Africans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26633544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Malaria Resistance</em></strong></p><p>
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For discussion of a possible relationship between a gln248-to-his (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11568350;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs11568350</a>) variant in the SLC40A1 gene and resistance to malaria, see <a href="/entry/611162">611162</a>.</p>
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<p><a href="#7" class="mim-tip-reference" title="Donovan, A., Lima, C. A., Pinkus, J. L., Pinkus, G. S., Zon, L. I., Robine, S., Andrews, N. C. <strong>The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis.</strong> Cell Metab. 1: 191-200, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16054062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16054062</a>] [<a href="https://doi.org/10.1016/j.cmet.2005.01.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16054062">Donovan et al. (2005)</a> found that knockout of the ferroportin gene in mice resulted in embryonic lethality, likely from a defect in iron transfer from the mother. Heterozygous animals were viable and showed a mild disruption of iron homeostasis. Mutant mice with ferroportin deleted in all tissues except extraembryonic visceral endoderm and placenta appeared normal at birth, but they developed anemia and abnormal iron accumulation in duodenal enterocytes, Kupffer cells and hepatocytes, and splenic macrophages. Mice with ferroportin deletion restricted to the intestines developed severe iron deficiency anemia. <a href="#7" class="mim-tip-reference" title="Donovan, A., Lima, C. A., Pinkus, J. L., Pinkus, G. S., Zon, L. I., Robine, S., Andrews, N. C. <strong>The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis.</strong> Cell Metab. 1: 191-200, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16054062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16054062</a>] [<a href="https://doi.org/10.1016/j.cmet.2005.01.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16054062">Donovan et al. (2005)</a> concluded that ferroportin is essential for prenatal and postnatal iron homeostasis, specifically in iron transfer across extraembryonic visceral endoderm, and iron export from enterocytes, macrophages, and hepatocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16054062" 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="Zohn, I. E., De Domenico, I., Pollock, A., Ward, D. M., Goodman, J. F., Liang, X., Sanchez, A. J., Niswander, L., Kaplan, J. <strong>The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease.</strong> Blood 109: 4174-4180, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17289807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17289807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17289807[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/10.1182/blood-2007-01-066068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17289807">Zohn et al. (2007)</a> reported the mouse flatiron (ffe) mutation, a his32-to-arg (H32R) substitution in Fpn that affected its localization and iron export activity. Similar to human patients with classic ferroportin disease, heterozygous ffe/+ mice exhibited iron loading on Kupffer cells, high serum ferritin, and low transferrin saturation. Using macrophages from ffe/+ mice and through expression of Fpn(ffe) in human embryonic kidney cells, <a href="#22" class="mim-tip-reference" title="Zohn, I. E., De Domenico, I., Pollock, A., Ward, D. M., Goodman, J. F., Liang, X., Sanchez, A. J., Niswander, L., Kaplan, J. <strong>The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease.</strong> Blood 109: 4174-4180, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17289807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17289807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17289807[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/10.1182/blood-2007-01-066068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17289807">Zohn et al. (2007)</a> showed that Fpn(ffe) acted in a dominant-negative manner and prevented wildtype Fpn from localizing on the cell surface and transporting iron. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17289807" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893662 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893662;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=rs104893662" 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=rs104893662" 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=RCV000005743" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005743" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005743</a>
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<p>In a large Dutch family with autosomal dominant hemochromatosis (HFE4; <a href="/entry/606069">606069</a>), <a href="#15" class="mim-tip-reference" title="Njajou, O. T., Vaessen, N., Joosse, M., Berghuis, B., van Dongen, J. W. F., Breuning, M. H., Snijders, P. J. L. M., Rutten, W. P. F., Sandkuijl, L. A., Oostra, B. A., van Duijn, C. M., Heutink, P. <strong>A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis.</strong> Nature Genet. 28: 213-214, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431687</a>] [<a href="https://doi.org/10.1038/90038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11431687">Njajou et al. (2001)</a> identified an A-to-C transversion at nucleotide 734 in exon 5 of the SLC40A1 gene, resulting in an asn144-to-his substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11431687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28939076 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939076;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=rs28939076" 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=rs28939076" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Italian family, <a href="#12" class="mim-tip-reference" title="Montosi, G., Donovan, A., Totaro, A., Garuti, C., Pignatti, E., Cassanelli, S., Trenor, C. C., Gasparini, P., Andrews, N. C., Pietrangelo, A. <strong>Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene.</strong> J. Clin. Invest. 108: 619-623, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11518736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11518736</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11518736[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI13468" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11518736">Montosi et al. (2001)</a> determined linkage of autosomal dominant hemochromatosis (HFE4; <a href="/entry/606069">606069</a>) to 2q32 and demonstrated a nonconservative missense mutation in the ferroportin gene: a GCC-to-GAC change resulting in an ala77-to-asp (A77D) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11518736" 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 147 Indian patients with thalassemia major and 65 cirrhotic controls, <a href="#1" class="mim-tip-reference" title="Agarwal, S., Sankar, V. H., Tewari, D., Pradhan, M. <strong>Ferroportin (SLC40A1) gene in thalassemic patients of Indian descent. (Letter)</strong> Clin. Genet. 70: 86-87, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16813613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16813613</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00644.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16813613">Agarwal et al. (2006)</a> analyzed the SLC40A1 gene and other modifier genes of iron hemostasis and identified the A77D mutation in 3 thalassemia patients, 2 heterozygotes and 1 homozygote. The mutation was not found in the control group. <a href="#1" class="mim-tip-reference" title="Agarwal, S., Sankar, V. H., Tewari, D., Pradhan, M. <strong>Ferroportin (SLC40A1) gene in thalassemic patients of Indian descent. (Letter)</strong> Clin. Genet. 70: 86-87, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16813613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16813613</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00644.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16813613">Agarwal et al. (2006)</a> stated that this was the first report of a ferroportin mutation in the Indian population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16813613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 HEMOCHROMATOSIS, TYPE 4</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">rs878854984 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs878854984;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=rs878854984" 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=rs878854984" 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=RCV000005747 OR RCV003407282" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005747, RCV003407282" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005747...</a>
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<p>In an Australian family with autosomal dominant hemochromatosis (HFE4; <a href="/entry/606069">606069</a>), <a href="#19" class="mim-tip-reference" title="Wallace, D. F., Pedersen, P., Dixon, J. L., Stephenson, P., Searle, J. W., Powell, L. W., Subramaniam, V. N. <strong>Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis.</strong> Blood 100: 692-694, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12091366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12091366</a>] [<a href="https://doi.org/10.1182/blood.v100.2.692" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12091366">Wallace et al. (2002)</a> found heterozygosity for a 3-bp (TTG) deletion in exon 5 of the FPN1 gene, resulting in the deletion of valine at position 162. They proposed that the deletion is a loss-of-function mutation that results in impaired iron homeostasis and leads to iron overload. The mutation was present in 2 brothers in whom the diagnosis was made at ages 56 and 73 years and who had hepatic fibrosis. It was also present in the first brother's children: his son, in whom the diagnosis was made at age 20 years and who had mild fibrosis, and his daughter, age 19 years, who had no hepatic abnormality. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12091366" 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 the United Kingdom, <a href="#5" class="mim-tip-reference" title="Devalia, V., Carter, K., Walker, A. P., Perkins, S. J., Worwood, M., May, A., Dooley, J. S. <strong>Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3).</strong> Blood 100: 695-697, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12091367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12091367</a>] [<a href="https://doi.org/10.1182/blood-2001-11-0132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12091367">Devalia et al. (2002)</a> found the same mutation in members of a family with autosomal dominant hemochromatosis. The proband was a 38-year-old woman who presented with fatigue and was found to have a high serum ferritin concentration and, by liver biopsy, heavy iron deposition in both hepatocytes and Kupffer cells. Venesection therapy was poorly tolerated (i.e., anemia developed), suggesting a defect in iron release from reticuloendothelial stores. The proband's sister likewise had high serum ferritin concentration, and MRI suggested iron accumulation in both the liver and spleen. Liver biopsy showed no fibrosis but marked iron accumulation in Kupffer cells. The combination of erythropoietin administration with phlebotomy permitted removal of iron without anemia. Although details were not provided, other members of the family were affected in a pedigree pattern consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12091367" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The same heterozygous 3-bp deletion in the FPN1 gene was reported by <a href="#17" class="mim-tip-reference" title="Roetto, A., Merryweather-Clarke, A. T., Daraio, F., Livesey, K., Pointon, J. J., Barbabietola, G., Piga, A., Mackie, P. H., Robson, K. J. H., Camaschella, C. <strong>A valine deletion of ferroportin 1: a common mutation in hemochromatosis type 4? (Letter)</strong> Blood 100: 733-734, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12123233/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12123233</a>] [<a href="https://doi.org/10.1182/blood-2002-03-0693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12123233">Roetto et al. (2002)</a> in 2 related Italian patients and in 1 unrelated British patient, suggesting that this is a particularly common mutation in type 4 hemochromatosis. <a href="#17" class="mim-tip-reference" title="Roetto, A., Merryweather-Clarke, A. T., Daraio, F., Livesey, K., Pointon, J. J., Barbabietola, G., Piga, A., Mackie, P. H., Robson, K. J. H., Camaschella, C. <strong>A valine deletion of ferroportin 1: a common mutation in hemochromatosis type 4? (Letter)</strong> Blood 100: 733-734, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12123233/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12123233</a>] [<a href="https://doi.org/10.1182/blood-2002-03-0693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12123233">Roetto et al. (2002)</a> suggested that haploinsufficiency for ferroportin-1 would be more limiting to iron transport in reticuloendothelial cells than in duodenal enterocytes, because the flux of iron through the reticuloendothelial macrophages far exceeds the flux of iron through the duodenal mucosa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12123233" 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="#2" class="mim-tip-reference" title="Cazzola, M., Cremonesi, L., Papaioannou, M., Soriani, N., Kioumi, A., Charalambidou, A., Paroni, R., Romtsou, K., Levi, S., Ferrari, M., Arosio, P., Christakis, J. <strong>Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3).</strong> Brit. J. Haemat. 119: 539-546, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12406098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12406098</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2002.03946.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12406098">Cazzola et al. (2002)</a> found the same mutation in a family with autosomal dominant hyperferritinemia in whom the proband showed selective iron accumulation in the Kupffer cells on liver biopsy. The mutation occurred in the region of nucleotides 780-791, which comprises 4 TTG repeats; the loss of 1 TTG unit was predicted to result in the deletion of 1 of 3 sequential valine residues, codons 160-162. This is a recurrent mutation, presumably due to slippage mispairing. Affected individuals showed marginally low serum iron and transferrin saturation. Serum ferritin levels were directly related to age, but were 10 to 20 times higher than normal. <a href="#2" class="mim-tip-reference" title="Cazzola, M., Cremonesi, L., Papaioannou, M., Soriani, N., Kioumi, A., Charalambidou, A., Paroni, R., Romtsou, K., Levi, S., Ferrari, M., Arosio, P., Christakis, J. <strong>Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3).</strong> Brit. J. Haemat. 119: 539-546, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12406098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12406098</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2002.03946.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12406098">Cazzola et al. (2002)</a> suggested that heterozygosity for this mutation represents the prototype of selective reticuloendothelial iron overload, and should be taken into account in the differential diagnosis of hereditary or congenital hyperferritinemias, such as hyperferritinemia-cataract syndrome (<a href="/entry/600886">600886</a>), which is due to mutations in the ferritin light chain gene (FTL; <a href="/entry/134790">134790</a>), or disorders of the ferritin heavy chain gene (FTH1; <a href="/entry/134770">134770</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12406098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893663 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893663;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=rs104893663" 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=rs104893663" 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=RCV000005745" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005745" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005745</a>
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<p>In a patient with type 4 hemochromatosis (HFE4; <a href="/entry/606069">606069</a>), <a href="#10" class="mim-tip-reference" title="Hetet, G., Devaux, I., Soufir, N., Grandchamp, B., Beaumont, C. <strong>Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations.</strong> Blood 102: 1904-1910, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12730114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12730114</a>] [<a href="https://doi.org/10.1182/blood-2003-02-0439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12730114">Hetet et al. (2003)</a> identified an asp157-to-gly (D157G) mutation in the SLC40A1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12730114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<strong>.0005 HEMOCHROMATOSIS, TYPE 4</strong>
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SLC40A1, GLN182HIS
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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> rs104893670 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893670;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/rs104893670?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=rs104893670" 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=rs104893670" 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=RCV000005746" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005746" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005746</a>
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<p>In a patient with type 4 hemochromatosis (HFE4; <a href="/entry/606069">606069</a>), <a href="#10" class="mim-tip-reference" title="Hetet, G., Devaux, I., Soufir, N., Grandchamp, B., Beaumont, C. <strong>Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations.</strong> Blood 102: 1904-1910, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12730114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12730114</a>] [<a href="https://doi.org/10.1182/blood-2003-02-0439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12730114">Hetet et al. (2003)</a> identified a gln182-to-his (Q182H) mutation in the SLC40A1 gene. The patient's daughter also had increased serum ferritin levels and was found to carry the Q182H mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12730114" 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="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 HEMOCHROMATOSIS, TYPE 4</strong>
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</h4>
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SLC40A1, GLY323VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893671 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893671;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=rs104893671" 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=rs104893671" 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=RCV000005748" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005748" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005748</a>
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<span class="mim-text-font">
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<p>In a patient with type 4 hemochromatosis (HFE4; <a href="/entry/606069">606069</a>), <a href="#10" class="mim-tip-reference" title="Hetet, G., Devaux, I., Soufir, N., Grandchamp, B., Beaumont, C. <strong>Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations.</strong> Blood 102: 1904-1910, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12730114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12730114</a>] [<a href="https://doi.org/10.1182/blood-2003-02-0439" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12730114">Hetet et al. (2003)</a> identified a gly323-to-val (G323V) mutation in the SLC40A1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12730114" 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="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 HEMOCHROMATOSIS, TYPE 4</strong>
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</span>
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</h4>
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<div style="float: left;">
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SLC40A1, ASP181VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893672 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893672;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=rs104893672" 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=rs104893672" 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=RCV000005749" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005749" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005749</a>
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<span class="mim-text-font">
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<p>In affected members of an Italian family with elevated serum ferritin and low hepcidin/ferritin ratios (HFE4; <a href="/entry/606069">606069</a>), <a href="#3" class="mim-tip-reference" title="Cremonesi, L., Forni, G. L., Soriani, N., Lamagna, M., Fermo, I., Daraio, F., Galli, A., Pietra, D., Malcovati, L., Ferrari, M., Camaschella, C., Cazzola, M. <strong>Genetic and clinical heterogeneity of ferroportin disease.</strong> Brit. J. Haemat. 131: 663-670, 2005. Note: Erratum: Brit. J. Haemat. 132: 806 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16351644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16351644</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2005.05815.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16351644">Cremonesi et al. (2005)</a> identified heterozygosity for an 846A-T transversion in exon 6 of the SLC40A1 gene, resulting in an asp181-to-val (D181V) substitution. A liver biopsy from the 34-year-old male proband revealed heavy iron deposition in both hepatocytes and Kupffer cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16351644" 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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<h4>
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<span class="mim-font">
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<strong>.0008 HEMOCHROMATOSIS, TYPE 4</strong>
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</span>
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</h4>
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</div>
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SLC40A1, GLY80VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893673 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893673;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=rs104893673" 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=rs104893673" 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=RCV000005750" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005750" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005750</a>
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<span class="mim-text-font">
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<p>In 3 affected members of an Italian family with elevated serum ferritin (HFE4; <a href="/entry/606069">606069</a>), <a href="#3" class="mim-tip-reference" title="Cremonesi, L., Forni, G. L., Soriani, N., Lamagna, M., Fermo, I., Daraio, F., Galli, A., Pietra, D., Malcovati, L., Ferrari, M., Camaschella, C., Cazzola, M. <strong>Genetic and clinical heterogeneity of ferroportin disease.</strong> Brit. J. Haemat. 131: 663-670, 2005. Note: Erratum: Brit. J. Haemat. 132: 806 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16351644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16351644</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2005.05815.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16351644">Cremonesi et al. (2005)</a> identified heterozygosity for a 543G-T transversion in exon 3 of the SLC40A1 gene, resulting in a gly80-to-val (G80V) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16351644" 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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<h4>
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<span class="mim-font">
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<strong>.0009 HEMOCHROMATOSIS, TYPE 4</strong>
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</span>
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</h4>
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SLC40A1, GLY267ASP
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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> rs104893664 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893664;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/rs104893664?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=rs104893664" 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=rs104893664" 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=RCV000005751" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005751" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005751</a>
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</span>
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<span class="mim-text-font">
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<p>In 6 affected members of family of Chinese descent with isolated elevated serum ferritin (HFE4; <a href="/entry/606069">606069</a>), <a href="#3" class="mim-tip-reference" title="Cremonesi, L., Forni, G. L., Soriani, N., Lamagna, M., Fermo, I., Daraio, F., Galli, A., Pietra, D., Malcovati, L., Ferrari, M., Camaschella, C., Cazzola, M. <strong>Genetic and clinical heterogeneity of ferroportin disease.</strong> Brit. J. Haemat. 131: 663-670, 2005. Note: Erratum: Brit. J. Haemat. 132: 806 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16351644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16351644</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2005.05815.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16351644">Cremonesi et al. (2005)</a> identified heterozygosity for a 1104G-A transition in exon 7 of the SLC40A1 gene, resulting in a gly267-to-asp (G267D) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16351644" 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>REFERENCES</strong>
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|
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<a id="1" class="mim-anchor"></a>
|
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<a id="Agarwal2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Agarwal, S., Sankar, V. H., Tewari, D., Pradhan, M.
|
|
<strong>Ferroportin (SLC40A1) gene in thalassemic patients of Indian descent. (Letter)</strong>
|
|
Clin. Genet. 70: 86-87, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16813613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16813613</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16813613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2006.00644.x" target="_blank">Full Text</a>]
|
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|
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|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Cazzola2002" class="mim-anchor"></a>
|
|
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|
|
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|
|
Cazzola, M., Cremonesi, L., Papaioannou, M., Soriani, N., Kioumi, A., Charalambidou, A., Paroni, R., Romtsou, K., Levi, S., Ferrari, M., Arosio, P., Christakis, J.
|
|
<strong>Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3).</strong>
|
|
Brit. J. Haemat. 119: 539-546, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12406098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12406098</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12406098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2002.03946.x" target="_blank">Full Text</a>]
|
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|
|
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|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Cremonesi2005" class="mim-anchor"></a>
|
|
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|
|
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|
|
Cremonesi, L., Forni, G. L., Soriani, N., Lamagna, M., Fermo, I., Daraio, F., Galli, A., Pietra, D., Malcovati, L., Ferrari, M., Camaschella, C., Cazzola, M.
|
|
<strong>Genetic and clinical heterogeneity of ferroportin disease.</strong>
|
|
Brit. J. Haemat. 131: 663-670, 2005. Note: Erratum: Brit. J. Haemat. 132: 806 only, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16351644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16351644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16351644" 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.1365-2141.2005.05815.x" target="_blank">Full Text</a>]
|
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|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="De Domenico2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
De Domenico, I., Ward, D. M., Nemeth, E., Vaughn, M. B., Musci, G., Ganz, T., Kaplan, J.
|
|
<strong>The molecular basis of ferroportin-linked hemochromatosis.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 8955-8960, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15956209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15956209</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15956209[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=15956209" 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.0503804102" target="_blank">Full Text</a>]
|
|
|
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|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Devalia2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Devalia, V., Carter, K., Walker, A. P., Perkins, S. J., Worwood, M., May, A., Dooley, J. S.
|
|
<strong>Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3).</strong>
|
|
Blood 100: 695-697, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12091367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12091367</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12091367" 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/10.1182/blood-2001-11-0132" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Donovan2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, Z., Law, T. C., Brugnara, C., Lux, S. E., Pinkus, G. S., Pinkus, J. L., Kingsley, P. D., Palis, J., Fleming, M. D., Andrews, N. C., Zon, L. I.
|
|
<strong>Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter.</strong>
|
|
Nature 403: 776-781, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10693807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10693807</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10693807" 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/10.1038/35001596" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Donovan2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Donovan, A., Lima, C. A., Pinkus, J. L., Pinkus, G. S., Zon, L. I., Robine, S., Andrews, N. C.
|
|
<strong>The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis.</strong>
|
|
Cell Metab. 1: 191-200, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16054062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16054062</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16054062" 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.cmet.2005.01.003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Fleming2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fleming, R. E., Sly, W. S.
|
|
<strong>Ferroportin mutation in autosomal dominant hemochromatosis: loss of function, gain in understanding.</strong>
|
|
J. Clin. Invest. 108: 521-522, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11518724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11518724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11518724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI13739" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Haile2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Haile, D. J.
|
|
<strong>Assignment of Slc11a3 to mouse chromosome 1 band 1B and SLC11A3 to human chromosome 2q21 by in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 88: 328-329, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10828623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10828623</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10828623" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000015522" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Hetet2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hetet, G., Devaux, I., Soufir, N., Grandchamp, B., Beaumont, C.
|
|
<strong>Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations.</strong>
|
|
Blood 102: 1904-1910, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12730114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12730114</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12730114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2003-02-0439" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="McKie2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., Hediger, M. A., Hentze, M. W., Simpson, R. J.
|
|
<strong>A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.</strong>
|
|
Molec. Cell 5: 299-309, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10882071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10882071</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10882071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s1097-2765(00)80425-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Montosi2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montosi, G., Donovan, A., Totaro, A., Garuti, C., Pignatti, E., Cassanelli, S., Trenor, C. C., Gasparini, P., Andrews, N. C., Pietrangelo, A.
|
|
<strong>Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene.</strong>
|
|
J. Clin. Invest. 108: 619-623, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11518736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11518736</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11518736[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=11518736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI13468" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Nairz2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nairz, M., Schleicher, U., Schroll, A., Sonnweber, T., Theurl, I., Ludwiczek, S., Talasz, H., Brandacher, G., Moser, P. L., Muckenthaler, M. U., Fang, F. C., Bogdan, C., Weiss, G.
|
|
<strong>Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection.</strong>
|
|
J. Exp. Med. 210: 855-873, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23630227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23630227</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23630227[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=23630227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.20121946" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Nemeth2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., Kaplan, J.
|
|
<strong>Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.</strong>
|
|
Science 306: 2090-2093, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15514116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15514116</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15514116" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1104742" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Njajou2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Njajou, O. T., Vaessen, N., Joosse, M., Berghuis, B., van Dongen, J. W. F., Breuning, M. H., Snijders, P. J. L. M., Rutten, W. P. F., Sandkuijl, L. A., Oostra, B. A., van Duijn, C. M., Heutink, P.
|
|
<strong>A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis.</strong>
|
|
Nature Genet. 28: 213-214, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431687</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11431687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/90038" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Pietrangelo1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pietrangelo, A., Montosi, G., Totaro, A., Garuti, C., Conte, D., Cassanelli, S., Fraquelli, M., Sardini, C., Vasta, F., Gasparini, P.
|
|
<strong>Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene.</strong>
|
|
New Eng. J. Med. 341: 725-732, 1999.
|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471458</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10471458" 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/10.1056/NEJM199909023411003" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Roetto2002" class="mim-anchor"></a>
|
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<div class="">
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<p class="mim-text-font">
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|
Roetto, A., Merryweather-Clarke, A. T., Daraio, F., Livesey, K., Pointon, J. J., Barbabietola, G., Piga, A., Mackie, P. H., Robson, K. J. H., Camaschella, C.
|
|
<strong>A valine deletion of ferroportin 1: a common mutation in hemochromatosis type 4? (Letter)</strong>
|
|
Blood 100: 733-734, 2002.
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|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12123233/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12123233</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12123233" 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/10.1182/blood-2002-03-0693" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Sangokoya2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sangokoya, C., Doss, J. F., Chi, J.-T.
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|
<strong>Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin.</strong>
|
|
PLoS Genet. 9: e1003408, 2013. Note: Electronic Article.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23593016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23593016</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23593016[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=23593016" 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/10.1371/journal.pgen.1003408" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Wallace2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wallace, D. F., Pedersen, P., Dixon, J. L., Stephenson, P., Searle, J. W., Powell, L. W., Subramaniam, V. N.
|
|
<strong>Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis.</strong>
|
|
Blood 100: 692-694, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12091366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12091366</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12091366" 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/10.1182/blood.v100.2.692" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Wallace2016" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wallace, D. F., Subramaniam, V. N.
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<strong>The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data.</strong>
|
|
Genet. Med. 18: 618-626, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26633544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26633544</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26633544" 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/gim.2015.140" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Zhang2018" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, D.-L., Wu, J., Shah, B. N., Greutelaers, K. C., Ghosh, M. C., Ollivierre, H., Su, X., Thuma, P. E., Bedu-Addo, G., Mockenhaupt, F. P., Gordeuk, V. R., Rouault, T. A.
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|
<strong>Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk.</strong>
|
|
Science 359: 1520-1523, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29599243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29599243</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29599243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.aal2022" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Zohn2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zohn, I. E., De Domenico, I., Pollock, A., Ward, D. M., Goodman, J. F., Liang, X., Sanchez, A. J., Niswander, L., Kaplan, J.
|
|
<strong>The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease.</strong>
|
|
Blood 109: 4174-4180, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17289807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17289807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17289807[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=17289807" 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/10.1182/blood-2007-01-066068" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 11/06/2018
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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Ada Hamosh - updated : 10/23/2018<br>Paul J. Converse - updated : 7/2/2014<br>Patricia A. Hartz - updated : 8/28/2013<br>Patricia A. Hartz - updated : 5/1/2008<br>Marla J. F. O'Neill - updated : 9/8/2006<br>Marla J. F. O'Neill - updated : 3/30/2006<br>Marla J. F. O'Neill - updated : 7/11/2005<br>Patricia A. Hartz - updated : 4/19/2005<br>Ada Hamosh - updated : 1/27/2005<br>Victor A. McKusick - updated : 11/26/2003<br>Victor A. McKusick - updated : 1/10/2003<br>Victor A. McKusick - updated : 9/26/2002<br>Victor A. McKusick - updated : 1/10/2002<br>Victor A. McKusick - updated : 6/22/2001<br>Joanna S. Amberger - updated : 8/7/2000<br>Stylianos E. Antonarakis - updated : 3/30/2000
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh : 3/6/2000
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 11/06/2018
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/24/2018<br>alopez : 10/23/2018<br>mgross : 07/14/2014<br>mcolton : 7/2/2014<br>mgross : 8/28/2013<br>mgross : 8/28/2013<br>terry : 3/15/2013<br>carol : 10/21/2010<br>mgross : 5/1/2008<br>wwang : 9/12/2006<br>terry : 9/8/2006<br>wwang : 3/31/2006<br>terry : 3/30/2006<br>wwang : 7/20/2005<br>terry : 7/11/2005<br>mgross : 4/20/2005<br>terry : 4/19/2005<br>wwang : 2/2/2005<br>terry : 1/27/2005<br>tkritzer : 12/8/2003<br>tkritzer : 12/3/2003<br>terry : 11/26/2003<br>carol : 3/13/2003<br>carol : 3/13/2003<br>terry : 3/12/2003<br>tkritzer : 1/14/2003<br>terry : 1/10/2003<br>carol : 10/1/2002<br>tkritzer : 9/27/2002<br>tkritzer : 9/26/2002<br>carol : 1/14/2002<br>terry : 1/10/2002<br>mgross : 6/27/2001<br>terry : 6/22/2001<br>carol : 8/21/2000<br>carol : 8/8/2000<br>joanna : 8/7/2000<br>alopez : 4/4/2000<br>mgross : 3/30/2000<br>alopez : 3/6/2000
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
|
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<strong>*</strong> 604653
|
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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|
|
SOLUTE CARRIER FAMILY 40 (IRON-REGULATED TRANSPORTER), MEMBER 1; SLC40A1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
FERROPORTIN 1; FPN1<br />
|
|
IRON-REGULATED TRANSPORTER 1; IREG1<br />
|
|
SOLUTE CARRIER FAMILY 11 (PROTON-COUPLED DIVALENT METAL ION TRANSPORTER), MEMBER 3, FORMERLY; SLC11A3, FORMERLY
|
|
</span>
|
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: SLC40A1</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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|
<strong>SNOMEDCT:</strong> 1303911001, 719975002;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 2q32.2
|
|
|
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:189,560,590-189,580,786 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
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</div>
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<div>
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<br />
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
2q32.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Hemochromatosis, type 4
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
606069
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
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|
|
</tbody>
|
|
</table>
|
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</div>
|
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</div>
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<div>
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<br />
|
|
</div>
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<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</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>Defects in iron absorption and utilization lead to iron deficiency and overload disorders. Adult mammals absorb iron through the duodenum, whereas embryos obtain iron through placental transport. Iron uptake from the intestinal lumen through the apical surface of the polarized duodenal enterocytes is mediated by the divalent metal transporter, DMT1 (600523). A second transporter had been postulated to export iron across the basolateral surface to the circulation. Donovan et al. (2000) used positional cloning to identify the gene responsible for the hypochromic anemia of the zebrafish mutant 'weissherbst.' The gene, which they called ferroportin-1 (fpn1), encodes a multiple-transmembrane domain protein expressed in the yolk sac that was a candidate for the elusive iron transporter. Zebrafish ferroportin-1 is required for the transport of iron from maternally-derived yolk stores to the circulation and functions as an iron exporter when expressed in Xenopus oocytes. </p><p>Donovan et al. (2000) isolated mouse and human ferroportin-1 cDNAs by RT-PCR of liver and placenta, respectively. Human ferroportin-1 is a protein of 571 amino acids. A conserved sequence, predicted to form a hairpin-loop structure typical of iron response elements (IREs), was identified in the 5-prime untranslated region of the cDNAs from all 3 species. Northern blot analysis showed the highest level of expression in human placenta, liver, spleen, and kidney. In mouse, primitive erythroblasts derived from the blood islands do not express ferroportin-1, whereas the trophoblast cells of the inner placenta express high levels of ferroportin-1. In the human placenta, ferroportin-1 protein was primarily expressed in a basal location within the syncytiotrophoblasts, suggesting that it transports iron from mother to embryo. Mammalian ferroportin-1 is also expressed at the basolateral surface of duodenal enterocytes. On the basis of basolateral expression pattern of ferroportin-1 in mammalian enterocytes and the implication that ferroportin-1 is required for intestinal iron absorption and iron transport in zebrafish, Donovan et al. (2000) suggested that the protein is probably involved in iron export from enterocytes in mammals. </p><p>Iron absorption by the duodenal mucosa is initiated by uptake of ferrous Fe(II) iron across the brush border membrane and culminates in transfer of the metal across the basolateral membrane to the portal vein circulation by an unknown mechanism. Using a subtractive cloning strategy and PCR analysis, McKie et al. (2000) isolated mouse and human duodenal cDNAs encoding FPN1, which they called iron-regulated transporter-1 (IREG1). The IREG1 protein contains 10 transmembrane domains and is localized to the basolateral membrane of polarized epithelial cells. IREG1 mRNA and protein expression are increased under conditions of increased iron absorption, and the 5-prime untranslated region of the IREG1 mRNA contains a functional IRE. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By FISH, Haile (2000) mapped the SLC40A1 gene to human chromosome 2q32 and mouse chromosome 1B. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>McKie et al. (2000) found that IREG1 stimulated iron efflux following expression in Xenopus oocytes. They concluded that IREG1 represents the long-sought duodenal iron export protein and is upregulated in the iron overload disease hereditary hemochromatosis (235200). </p><p>Nemeth et al. (2004) reported that hepcidin (606464) bound to ferroportin in tissue culture cells. After binding, ferroportin was internalized and degraded, leading to decreased export of cellular iron. Nemeth et al. (2004) postulated that the posttranslational regulation of ferroportin by hepcidin may complete a homeostatic loop regulating iron plasma levels and the tissue distribution of iron. </p><p>Sangokoya et al. (2013) stated that FPN expression is downregulated in an iron-dependent manner by binding of iron regulatory protein (IRP; see 100880) to the IRE in the 5-prime UTR of the FPN transcript. Using a reporter gene assay, they confirmed that FPN expression decreased during iron depletion and increased significantly during iron supplementation in human HepG2 hepatocytes. Sangokoya et al. (2013) also identified a regulatory region in the 3-prime UTR of FPN that bound the microRNA MIR485-3p (615385). MIR485-3p was induced during iron deficiency in human cell lines, and MIR485-3p binding to the 3-prime UTR of the FPN transcript repressed FPN translation, leading to increased cellular ferritin (see 134790) levels and increased cellular iron. Inhibition of MIR485-3p activity or mutation of the MIR485-3p-binding site in the FPN 3-prime UTR relieved FPN repression and led to cellular iron deficiency. IRP and MIR485-3p downregulated FPN expression in an additive manner. </p><p>Nairz et al. (2013) found that macrophages from mice lacking nitric oxide synthase-2 (NOS2; 163730) displayed reduced expression of Fpn1. Nitric oxide upregulated FPN1 expression in mouse and human cells. Nos2-null mouse macrophages had increased iron content due to reduced Fpn1 activity. Reduced Fpn1 expression allowed enhanced iron acquisition by the intracellular bacterium Salmonella typhimurium. Mice lacking Nos2 or mice in which Nos2 activity was inhibited had increased iron accumulation in spleen and spleen macrophages. Lack of nitric oxide formation resulted in impaired Nrf2 (NFE2L2; 600492) expression and, consequently, reduced Fpn1 transcription and cellular iron export. Infection of Nos2-null mice or macrophages with S. typhimurium led not only to increased iron accumulation, but also to reduced Tnf (191160), Il2 (147680), and Ifng (147570) expression and impaired pathogen control, all of which could be restored by treatment with iron chelators or overexpression of Fpn1 or Nrf2. Nairz et al. (2013) concluded that iron accumulation in Nos2-null macrophages counteracts a proinflammatory host response and that the protective effects of nitric oxide partially result from its ability to prevent iron overload in macrophages. </p><p>Zhang et al. (2018) found that ferroportin is highly abundant in mature red blood cells and that its activity is inhibited by iron supplementation and hepcidin. Additional deletion of the FPN1 gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. Fpn knockout increased non-heme iron content and intracellular ferritin levels in erythroblasts and resulted in a mild compensated anemia and extramedullary erythropoiesis. The anemia was not caused by a defect in erythroblast differentiation, but instead by the increased fragility and hemolysis of mature red blood cells, as evidenced by the 2.5-fold increase of free plasma hemoglobin after storage at 4 degrees C for 20 hours. Zhang et al. (2018) intravenously injected wildtype and Fpn knockout mice with Plasmodium yoelii, a lethal murine malaria strain. The knockout mice had 60% more parasite-infected red blood cells than wildtype mice on multiple successive days after infection, and died more rapidly after infection. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>By mutation analysis of all exons, intron-exon boundaries, and the 5-prime and 3-prime untranslated region (including the IRE) of the SLC40A1 gene in a Dutch family with hemochromatosis type 4 (HFE4; 606069), Njajou et al. (2001) identified a heterozygous A-to-C transversion at nucleotide 734 in exon 5 in all affected individuals. The mutation resulted in an asn144-to-his substitution (604653.0001). The substituted asn is a highly conserved amino acid in vertebrates. </p><p>Independently, in an Italian family with autosomal dominant hemochromatosis originally reported by Pietrangelo et al. (1999), Montosi et al. (2001) mapped the disease locus responsible for autosomal dominant hemochromatosis to 2q32 and recognized ferroportin as a compelling positional candidate for the site of the mutation. They identified a mutation in the SLC40A1 gene (604653.0002). They pointed out that the distinguishing features of this disorder, in addition to autosomal dominant inheritance, is early iron accumulation in reticuloendothelial cells and a marked increase in serum ferritin before elevation of the transferrin saturation. Fleming and Sly (2001) commented that haploinsufficiency for ferroportin would (at least initially) favor low serum iron by decreasing dietary iron absorption and by impairing iron release from macrophages. This could explain the low transferrin saturations, the anemia early in life, and the sensitivity to phlebotomy observed in many of these patients. The hepatocellular iron loading might be explained by the secondary effects of the 'erythropoietic regulator' stimulating intestinal iron absorption, or possibly by ferroportin-1 haploinsufficiency in hepatocytes. </p><p>Unexplained hyperferritinemia is a common clinical finding, even in asymptomatic persons. When early-onset bilateral cataracts are also present, hereditary hyperferritinemia-cataract syndrome (600886), resulting from a heterozygous point mutation in the L ferritin (FTL; 134790) IRE sequence, can be suspected. Hetet et al. (2003) sequenced exon 1 of the FTL gene in 52 DNA samples from patients referred for molecular diagnosis of hyperferritinemia-cataract syndrome. They identified 24 samples with a point mutation or deletion in the IRE. For the 28 samples in which no IRE mutation was present, they also genotyped for mutations in the HFE gene (613609) and sequenced both the H ferritin (FTH1; 134770) and SLC40A1 genes. They found an increased frequency (12 of 28) of heterozygotes for the HFE his63-to-asp mutation (H63D; 613609.0002), but no H ferritin mutations. They identified 3 novel SLC40A1 mutations (604653.0004-604653.0006), suggesting that these patients had dominant type 4 hemochromatosis. The study demonstrated that both L ferritin IRE and SLC40A1 mutations can account for isolated hyperferritinemia. The presence of cataract does not permit the unambiguous identification of patients with hereditary hyperferritinemia-cataract syndrome, although the existence of a family history of cataract was only encountered in these patients. This raised the possibility that lens ferritin accumulation may be a factor contributing to age-related cataract in the general population. </p><p>In transfection experiments using HEK 293T cells, De Domenico et al. (2005) showed that known human mutations introduced into the mouse Slc40a1 gene generate proteins that either are defective in cell surface localization or have a decreased ability to be internalized and degraded in response to hepcidin. Coimmunoprecipitation studies revealed that ferroportin is multimeric. Both wildtype and mutant ferroportin participated in the multimer, and mutant ferroportin affected the localization of wildtype ferroportin, its stability, and its response to hepcidin. De Domenico et al. (2005) concluded that the behavior of mutant ferroportin in cell culture and its ability to act as a dominant negative explain the dominant inheritance of the disease as well as the different patient phenotypes. </p><p>Cremonesi et al. (2005) studied 2 Italian families and 1 of Chinese descent with elevated serum ferritin levels and identified heterozygosity for 3 different mutations in the SLC40A1 gene, respectively. The authors noted the variability in phenotypes between the families and suggested that the mutation (604653.0007) in the first Italian family, in which the proband had a liver biopsy showing heavy iron deposition in both hepatocytes and Kupffer cells, likely caused decreased responsiveness to hepcidin, whereas the mutations (604653.0008 and 604653.0009) in the latter 2 families likely caused defective localization of the protein to the cell surface. </p><p>Wallace and Subramaniam (2016) reviewed 161 variants previously associated with any form of hereditary hemochromatosis and found that 43 were represented among next-generation sequence public databases including ESP, 1000 Genomes Project, and ExAC. The frequency of the C282Y mutation in HFE (613609.0001) matched previous estimates from similar populations. Of the non-HFE forms of iron overload, TFR2 (604720)-, HFE2 (608374)-, and HAMP (606464)-related forms were extremely rare, with pathogenic allele frequencies in the range of 0.00007 to 0.0005. However, SLC40A1 variants were identified in several populations (pathogenic allele frequency 0.0004), being most prevalent among Africans. </p><p><strong><em>Malaria Resistance</em></strong></p><p>
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For discussion of a possible relationship between a gln248-to-his (rs11568350) variant in the SLC40A1 gene and resistance to malaria, see 611162.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Donovan et al. (2005) found that knockout of the ferroportin gene in mice resulted in embryonic lethality, likely from a defect in iron transfer from the mother. Heterozygous animals were viable and showed a mild disruption of iron homeostasis. Mutant mice with ferroportin deleted in all tissues except extraembryonic visceral endoderm and placenta appeared normal at birth, but they developed anemia and abnormal iron accumulation in duodenal enterocytes, Kupffer cells and hepatocytes, and splenic macrophages. Mice with ferroportin deletion restricted to the intestines developed severe iron deficiency anemia. Donovan et al. (2005) concluded that ferroportin is essential for prenatal and postnatal iron homeostasis, specifically in iron transfer across extraembryonic visceral endoderm, and iron export from enterocytes, macrophages, and hepatocytes. </p><p>Zohn et al. (2007) reported the mouse flatiron (ffe) mutation, a his32-to-arg (H32R) substitution in Fpn that affected its localization and iron export activity. Similar to human patients with classic ferroportin disease, heterozygous ffe/+ mice exhibited iron loading on Kupffer cells, high serum ferritin, and low transferrin saturation. Using macrophages from ffe/+ mice and through expression of Fpn(ffe) in human embryonic kidney cells, Zohn et al. (2007) showed that Fpn(ffe) acted in a dominant-negative manner and prevented wildtype Fpn from localizing on the cell surface and transporting iron. </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>ALLELIC VARIANTS</strong>
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</span>
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<strong>9 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 HEMOCHROMATOSIS, TYPE 4</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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SLC40A1, ASN144HIS
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<br />
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SNP: rs104893662,
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ClinVar: RCV000005743
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a large Dutch family with autosomal dominant hemochromatosis (HFE4; 606069), Njajou et al. (2001) identified an A-to-C transversion at nucleotide 734 in exon 5 of the SLC40A1 gene, resulting in an asn144-to-his substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 HEMOCHROMATOSIS, TYPE 4</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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SLC40A1, ALA77ASP
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<br />
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SNP: rs28939076,
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ClinVar: RCV000005744
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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 Italian family, Montosi et al. (2001) determined linkage of autosomal dominant hemochromatosis (HFE4; 606069) to 2q32 and demonstrated a nonconservative missense mutation in the ferroportin gene: a GCC-to-GAC change resulting in an ala77-to-asp (A77D) substitution. </p><p>In 147 Indian patients with thalassemia major and 65 cirrhotic controls, Agarwal et al. (2006) analyzed the SLC40A1 gene and other modifier genes of iron hemostasis and identified the A77D mutation in 3 thalassemia patients, 2 heterozygotes and 1 homozygote. The mutation was not found in the control group. Agarwal et al. (2006) stated that this was the first report of a ferroportin mutation in the Indian population. </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 HEMOCHROMATOSIS, TYPE 4</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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SLC40A1, 3-BP DEL, VAL162DEL
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<br />
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SNP: rs878854984,
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ClinVar: RCV000005747, RCV003407282
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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 family with autosomal dominant hemochromatosis (HFE4; 606069), Wallace et al. (2002) found heterozygosity for a 3-bp (TTG) deletion in exon 5 of the FPN1 gene, resulting in the deletion of valine at position 162. They proposed that the deletion is a loss-of-function mutation that results in impaired iron homeostasis and leads to iron overload. The mutation was present in 2 brothers in whom the diagnosis was made at ages 56 and 73 years and who had hepatic fibrosis. It was also present in the first brother's children: his son, in whom the diagnosis was made at age 20 years and who had mild fibrosis, and his daughter, age 19 years, who had no hepatic abnormality. </p><p>In the United Kingdom, Devalia et al. (2002) found the same mutation in members of a family with autosomal dominant hemochromatosis. The proband was a 38-year-old woman who presented with fatigue and was found to have a high serum ferritin concentration and, by liver biopsy, heavy iron deposition in both hepatocytes and Kupffer cells. Venesection therapy was poorly tolerated (i.e., anemia developed), suggesting a defect in iron release from reticuloendothelial stores. The proband's sister likewise had high serum ferritin concentration, and MRI suggested iron accumulation in both the liver and spleen. Liver biopsy showed no fibrosis but marked iron accumulation in Kupffer cells. The combination of erythropoietin administration with phlebotomy permitted removal of iron without anemia. Although details were not provided, other members of the family were affected in a pedigree pattern consistent with autosomal dominant inheritance. </p><p>The same heterozygous 3-bp deletion in the FPN1 gene was reported by Roetto et al. (2002) in 2 related Italian patients and in 1 unrelated British patient, suggesting that this is a particularly common mutation in type 4 hemochromatosis. Roetto et al. (2002) suggested that haploinsufficiency for ferroportin-1 would be more limiting to iron transport in reticuloendothelial cells than in duodenal enterocytes, because the flux of iron through the reticuloendothelial macrophages far exceeds the flux of iron through the duodenal mucosa. </p><p>Cazzola et al. (2002) found the same mutation in a family with autosomal dominant hyperferritinemia in whom the proband showed selective iron accumulation in the Kupffer cells on liver biopsy. The mutation occurred in the region of nucleotides 780-791, which comprises 4 TTG repeats; the loss of 1 TTG unit was predicted to result in the deletion of 1 of 3 sequential valine residues, codons 160-162. This is a recurrent mutation, presumably due to slippage mispairing. Affected individuals showed marginally low serum iron and transferrin saturation. Serum ferritin levels were directly related to age, but were 10 to 20 times higher than normal. Cazzola et al. (2002) suggested that heterozygosity for this mutation represents the prototype of selective reticuloendothelial iron overload, and should be taken into account in the differential diagnosis of hereditary or congenital hyperferritinemias, such as hyperferritinemia-cataract syndrome (600886), which is due to mutations in the ferritin light chain gene (FTL; 134790), or disorders of the ferritin heavy chain gene (FTH1; 134770). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 HEMOCHROMATOSIS, TYPE 4</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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SLC40A1, ASP157GLY
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<br />
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SNP: rs104893663,
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ClinVar: RCV000005745
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with type 4 hemochromatosis (HFE4; 606069), Hetet et al. (2003) identified an asp157-to-gly (D157G) mutation in the SLC40A1 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>.0005 HEMOCHROMATOSIS, TYPE 4</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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SLC40A1, GLN182HIS
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<br />
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SNP: rs104893670,
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gnomAD: rs104893670,
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ClinVar: RCV000005746
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with type 4 hemochromatosis (HFE4; 606069), Hetet et al. (2003) identified a gln182-to-his (Q182H) mutation in the SLC40A1 gene. The patient's daughter also had increased serum ferritin levels and was found to carry the Q182H mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 HEMOCHROMATOSIS, TYPE 4</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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SLC40A1, GLY323VAL
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<br />
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SNP: rs104893671,
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ClinVar: RCV000005748
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with type 4 hemochromatosis (HFE4; 606069), Hetet et al. (2003) identified a gly323-to-val (G323V) mutation in the SLC40A1 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>.0007 HEMOCHROMATOSIS, TYPE 4</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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SLC40A1, ASP181VAL
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<br />
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SNP: rs104893672,
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ClinVar: RCV000005749
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In affected members of an Italian family with elevated serum ferritin and low hepcidin/ferritin ratios (HFE4; 606069), Cremonesi et al. (2005) identified heterozygosity for an 846A-T transversion in exon 6 of the SLC40A1 gene, resulting in an asp181-to-val (D181V) substitution. A liver biopsy from the 34-year-old male proband revealed heavy iron deposition in both hepatocytes and Kupffer cells. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0008 HEMOCHROMATOSIS, TYPE 4</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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SLC40A1, GLY80VAL
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<br />
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SNP: rs104893673,
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ClinVar: RCV000005750
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 affected members of an Italian family with elevated serum ferritin (HFE4; 606069), Cremonesi et al. (2005) identified heterozygosity for a 543G-T transversion in exon 3 of the SLC40A1 gene, resulting in a gly80-to-val (G80V) substitution. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0009 HEMOCHROMATOSIS, TYPE 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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SLC40A1, GLY267ASP
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<br />
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|
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SNP: rs104893664,
|
|
|
|
|
|
gnomAD: rs104893664,
|
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|
|
|
|
ClinVar: RCV000005751
|
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 6 affected members of family of Chinese descent with isolated elevated serum ferritin (HFE4; 606069), Cremonesi et al. (2005) identified heterozygosity for a 1104G-A transition in exon 7 of the SLC40A1 gene, resulting in a gly267-to-asp (G267D) substitution. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Agarwal, S., Sankar, V. H., Tewari, D., Pradhan, M.
|
|
<strong>Ferroportin (SLC40A1) gene in thalassemic patients of Indian descent. (Letter)</strong>
|
|
Clin. Genet. 70: 86-87, 2006.
|
|
|
|
|
|
[PubMed: 16813613]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2006.00644.x]
|
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</p>
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</li>
|
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<li>
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<p class="mim-text-font">
|
|
Cazzola, M., Cremonesi, L., Papaioannou, M., Soriani, N., Kioumi, A., Charalambidou, A., Paroni, R., Romtsou, K., Levi, S., Ferrari, M., Arosio, P., Christakis, J.
|
|
<strong>Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3).</strong>
|
|
Brit. J. Haemat. 119: 539-546, 2002.
|
|
|
|
|
|
[PubMed: 12406098]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2002.03946.x]
|
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|
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</p>
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cremonesi, L., Forni, G. L., Soriani, N., Lamagna, M., Fermo, I., Daraio, F., Galli, A., Pietra, D., Malcovati, L., Ferrari, M., Camaschella, C., Cazzola, M.
|
|
<strong>Genetic and clinical heterogeneity of ferroportin disease.</strong>
|
|
Brit. J. Haemat. 131: 663-670, 2005. Note: Erratum: Brit. J. Haemat. 132: 806 only, 2006.
|
|
|
|
|
|
[PubMed: 16351644]
|
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|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.2005.05815.x]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
De Domenico, I., Ward, D. M., Nemeth, E., Vaughn, M. B., Musci, G., Ganz, T., Kaplan, J.
|
|
<strong>The molecular basis of ferroportin-linked hemochromatosis.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 8955-8960, 2005.
|
|
|
|
|
|
[PubMed: 15956209]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0503804102]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Devalia, V., Carter, K., Walker, A. P., Perkins, S. J., Worwood, M., May, A., Dooley, J. S.
|
|
<strong>Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3).</strong>
|
|
Blood 100: 695-697, 2002.
|
|
|
|
|
|
[PubMed: 12091367]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2001-11-0132]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, Z., Law, T. C., Brugnara, C., Lux, S. E., Pinkus, G. S., Pinkus, J. L., Kingsley, P. D., Palis, J., Fleming, M. D., Andrews, N. C., Zon, L. I.
|
|
<strong>Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter.</strong>
|
|
Nature 403: 776-781, 2000.
|
|
|
|
|
|
[PubMed: 10693807]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/35001596]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donovan, A., Lima, C. A., Pinkus, J. L., Pinkus, G. S., Zon, L. I., Robine, S., Andrews, N. C.
|
|
<strong>The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis.</strong>
|
|
Cell Metab. 1: 191-200, 2005.
|
|
|
|
|
|
[PubMed: 16054062]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cmet.2005.01.003]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fleming, R. E., Sly, W. S.
|
|
<strong>Ferroportin mutation in autosomal dominant hemochromatosis: loss of function, gain in understanding.</strong>
|
|
J. Clin. Invest. 108: 521-522, 2001.
|
|
|
|
|
|
[PubMed: 11518724]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI13739]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Haile, D. J.
|
|
<strong>Assignment of Slc11a3 to mouse chromosome 1 band 1B and SLC11A3 to human chromosome 2q21 by in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 88: 328-329, 2000.
|
|
|
|
|
|
[PubMed: 10828623]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000015522]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hetet, G., Devaux, I., Soufir, N., Grandchamp, B., Beaumont, C.
|
|
<strong>Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations.</strong>
|
|
Blood 102: 1904-1910, 2003.
|
|
|
|
|
|
[PubMed: 12730114]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2003-02-0439]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., Hediger, M. A., Hentze, M. W., Simpson, R. J.
|
|
<strong>A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.</strong>
|
|
Molec. Cell 5: 299-309, 2000.
|
|
|
|
|
|
[PubMed: 10882071]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1097-2765(00)80425-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montosi, G., Donovan, A., Totaro, A., Garuti, C., Pignatti, E., Cassanelli, S., Trenor, C. C., Gasparini, P., Andrews, N. C., Pietrangelo, A.
|
|
<strong>Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene.</strong>
|
|
J. Clin. Invest. 108: 619-623, 2001.
|
|
|
|
|
|
[PubMed: 11518736]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI13468]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nairz, M., Schleicher, U., Schroll, A., Sonnweber, T., Theurl, I., Ludwiczek, S., Talasz, H., Brandacher, G., Moser, P. L., Muckenthaler, M. U., Fang, F. C., Bogdan, C., Weiss, G.
|
|
<strong>Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection.</strong>
|
|
J. Exp. Med. 210: 855-873, 2013.
|
|
|
|
|
|
[PubMed: 23630227]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20121946]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., Kaplan, J.
|
|
<strong>Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.</strong>
|
|
Science 306: 2090-2093, 2004.
|
|
|
|
|
|
[PubMed: 15514116]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1104742]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Njajou, O. T., Vaessen, N., Joosse, M., Berghuis, B., van Dongen, J. W. F., Breuning, M. H., Snijders, P. J. L. M., Rutten, W. P. F., Sandkuijl, L. A., Oostra, B. A., van Duijn, C. M., Heutink, P.
|
|
<strong>A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis.</strong>
|
|
Nature Genet. 28: 213-214, 2001.
|
|
|
|
|
|
[PubMed: 11431687]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/90038]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pietrangelo, A., Montosi, G., Totaro, A., Garuti, C., Conte, D., Cassanelli, S., Fraquelli, M., Sardini, C., Vasta, F., Gasparini, P.
|
|
<strong>Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene.</strong>
|
|
New Eng. J. Med. 341: 725-732, 1999.
|
|
|
|
|
|
[PubMed: 10471458]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199909023411003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roetto, A., Merryweather-Clarke, A. T., Daraio, F., Livesey, K., Pointon, J. J., Barbabietola, G., Piga, A., Mackie, P. H., Robson, K. J. H., Camaschella, C.
|
|
<strong>A valine deletion of ferroportin 1: a common mutation in hemochromatosis type 4? (Letter)</strong>
|
|
Blood 100: 733-734, 2002.
|
|
|
|
|
|
[PubMed: 12123233]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2002-03-0693]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sangokoya, C., Doss, J. F., Chi, J.-T.
|
|
<strong>Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin.</strong>
|
|
PLoS Genet. 9: e1003408, 2013. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 23593016]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1371/journal.pgen.1003408]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. F., Pedersen, P., Dixon, J. L., Stephenson, P., Searle, J. W., Powell, L. W., Subramaniam, V. N.
|
|
<strong>Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis.</strong>
|
|
Blood 100: 692-694, 2002.
|
|
|
|
|
|
[PubMed: 12091366]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood.v100.2.692]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. F., Subramaniam, V. N.
|
|
<strong>The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data.</strong>
|
|
Genet. Med. 18: 618-626, 2016.
|
|
|
|
|
|
[PubMed: 26633544]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/gim.2015.140]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, D.-L., Wu, J., Shah, B. N., Greutelaers, K. C., Ghosh, M. C., Ollivierre, H., Su, X., Thuma, P. E., Bedu-Addo, G., Mockenhaupt, F. P., Gordeuk, V. R., Rouault, T. A.
|
|
<strong>Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk.</strong>
|
|
Science 359: 1520-1523, 2018.
|
|
|
|
|
|
[PubMed: 29599243]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.aal2022]
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|
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|
</p>
|
|
</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Zohn, I. E., De Domenico, I., Pollock, A., Ward, D. M., Goodman, J. F., Liang, X., Sanchez, A. J., Niswander, L., Kaplan, J.
|
|
<strong>The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease.</strong>
|
|
Blood 109: 4174-4180, 2007.
|
|
|
|
|
|
[PubMed: 17289807]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2007-01-066068]
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</p>
|
|
</li>
|
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|
|
</ol>
|
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<div>
|
|
<br />
|
|
</div>
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|
</div>
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</div>
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<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
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Ada Hamosh - updated : 11/06/2018<br>Ada Hamosh - updated : 10/23/2018<br>Paul J. Converse - updated : 7/2/2014<br>Patricia A. Hartz - updated : 8/28/2013<br>Patricia A. Hartz - updated : 5/1/2008<br>Marla J. F. O'Neill - updated : 9/8/2006<br>Marla J. F. O'Neill - updated : 3/30/2006<br>Marla J. F. O'Neill - updated : 7/11/2005<br>Patricia A. Hartz - updated : 4/19/2005<br>Ada Hamosh - updated : 1/27/2005<br>Victor A. McKusick - updated : 11/26/2003<br>Victor A. McKusick - updated : 1/10/2003<br>Victor A. McKusick - updated : 9/26/2002<br>Victor A. McKusick - updated : 1/10/2002<br>Victor A. McKusick - updated : 6/22/2001<br>Joanna S. Amberger - updated : 8/7/2000<br>Stylianos E. Antonarakis - updated : 3/30/2000
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