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453 lines
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<span>HFE</span>
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<div class="rprt"><h1 class="g_title"><span class="gn"><em>HFE</em></span> homeostatic iron regulator</h1><span class="geneid">Gene ID: 3077, updated on
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4-Mar-2025</span><br /><span class="geneid">Gene type: protein coding</span><br /><span class="known-as"><em>Also known as: </em>HH; HFE1; HLA-H; MVCD7; TFQTL2</span><ul class="inline-list" style="padding-left:0;"><li><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=3077[geneid]" data-ga-label="see_all_available_tests">See all available tests in GTR for this gene</a></li><li><a href="/gene/3077/" ref="log_uid=3077&ncbi_uid=3077" data-ga-label="go_to_complete_gene_record">Go to complete Gene record for HFE</a></li><li><a href="/variation/view/?assm=GCF_000001405.25&q=HFE[gene]" ref="ncbi_uid=3077" data-ga-label="go_to_variation_viewer">Go to Variation Viewer for HFE variants</a></li></ul><h2>Summary</h2><p>The protein encoded by this gene is a membrane protein that is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). It is thought that this protein functions to regulate iron absorption by regulating the interaction of the transferrin receptor with transferrin. The iron storage disorder, hereditary haemochromatosis, is a recessive genetic disorder that results from defects in this gene. [provided by RefSeq, May 2022]</p><div id="associated-conditions"><h2>Associated conditions</h2><p><a href="/gtr/all/tests/?term=3077[geneid]" data-ga-label="see_all_available_tests">See all available tests in GTR for this gene</a></p><div class="associated-conditions-table"><table class="jig-ncbigrid gtr-associated-cond"><thead><tr><th class="description">Description</th><th>Tests</th></tr></thead><tbody><tr><td>A genome-wide association study of red blood cell traits using the electronic medical record.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Biological, clinical and population relevance of 95 loci for blood lipids.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Common variants at 10 genomic loci influence hemoglobin A&amp;#x000e2;&amp;#x00082;&amp;#x00081;(C) levels via glycemic and nonglycemic pathways.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Common variants in TMPRSS6 are associated with iron status and erythrocyte volume.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Discovery and refinement of loci associated with lipid levels.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Genome-wide admixture and association study of serum iron, ferritin, transferrin saturation and total iron binding capacity in African Americans.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Genome-wide association study identifies genetic loci associated with iron deficiency.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Genome-wide association study identifies two loci strongly affecting transferrin glycosylation.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Genome-wide association study of hematological and biochemical traits in a Japanese population.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td><a href="/gtr/conditions/C3469186" ref="ncbi_uid=3077&link_uid=C3469186" data-ga-label="condition">Hemochromatosis type 1</a><div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">MedGen: <a href="/medgen/C3469186" ref="ncbi_uid=3077&link_uid=C3469186" data-ga-label="medgen">C3469186</a></span><span class="gtr-associated-cond-extra-i">OMIM: <a href="https://www.ncbi.nlm.nih.gov/omim/235200" ref="ncbi_uid=3077" data-ga-label="omim"> 235200</a></span><span class="gtr-associated-cond-extra-i">GeneReviews: <a href="/books/NBK1440" ref="ncbi_uid=3077" data-ga-label="gene_reviews">HFE-Related Hemochromatosis</a></span></div></td><td><a href="/gtr/all/labs/?term=C3469186[DISCUI]" ref="ncbi_uid=3077" data-ga-label="labs">See labs</a></td></tr><tr><td>Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Sequence variants in three loci influence monocyte counts and erythrocyte volume.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Seventy-five genetic loci influencing the human red blood cell.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr><tr><td>Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels.<div class="gtr-associated-cond-extra"><span class="gtr-associated-cond-extra-i">GeneReviews: <span>Not available</span></span></div></td><td></td></tr></tbody></table></div></div><div id="genomic-context"><h2>Genomic context</h2><div class="map_location_wr"><div class="ch_location-wr"><dl class="chr_location"><dt>Location:</dt><dd>6p22.2</dd></dl><dl class="chr_location"><dt>Sequence: </dt><dd>Chromosome: 6; NC_000006.12 (26087429..26098343)</dd></dl><dl class="chr_location"><dt>Total number of exons:</dt><dd>7</dd></dl></div><div class="note-link"></div></div><div class="viewer"><div class="choose"><label for="accession" class="label">Genomic Sequence </label><select name="accessionList" sid="1" id="accessionList"><option value="NC_000006.12_26087428_26098342" data-assembly="GRCh38.p14">NC_000006 Chromosome 6 Reference GRCh38.p14 Primary Assembly (location A)</option><option value="NC_000006.11_26087656_26098570" data-assembly="GRCh37.p13">NC_000006 Chromosome 6 Reference GRCh37.p13 Primary Assembly (location B)</option><option value="NC_060930.1_25955570_25966490" data-assembly="T2T-CHM13v2.0">NC_060930 Chromosome 6 Alternate T2T-CHM13v2.0 (location A)</option><option value="NG_008720.2_5000_12960" data-assembly="">NG_008720 RefSeqGene</option></select></div><script type="text/javascript" src="/projects/sviewer/js/sviewer.js" id="autoload"></script><div id="NC_000006" class="divAccession"><div class="seq-viewer"><p class="note-link"><strong>Go to nucleotide</strong><a href="/nuccore/NC_000006.12?report=graph&from=26085791&to=26099979&tracks=[key:sequence_track,name:Sequence,display_name:Sequence,category:Sequence,annots:Sequence,ShowLabel:false][key:gene_model_track,name:Genes---Unnamed,display_name:Genes,annots:Unnamed,Options:MergePairs,SNPs:false,CDSProductFeats:true,ShowLabelsForAllFeatures:true,HighlightMode:2][key:feature_track,name:Genes---other,display_name:Genes - other,subkey:ncRNA,annots:other,Layout:Adaptive][key:feature_track,name:Genes---tRNA,display_name:Genes - tRNA,subkey:tRNA,annots:tRNA,Layout:Adaptive][key:SNP_track,name:SNP,annots:SNP,Layout:Adaptive][key:SNP_Bins_track,name:Clinical Variants][key:SNP_Bins_track,name:Cited Variants][key:GWAS_track,name:GWAS Tracks,display_name:Association Results]" title="Nucleotide graphic report" ref="ordinalpos=1&ncbi_uid=&link_uid=NC_000006.12">Graphics</a> <a href="/nuccore/NC_000006.12?report=fasta&from=26085791&to=26099979" title="Nucleotide graphic report" ref="ordinalpos=1&ncbi_uid=&link_uid=NC_000006.12">FASTA</a> <a href="/nuccore/NC_000006.12?report=genbank&from=26085791&to=26099979" title="Nucleotide GenBank report" ref="ordinalpos=1&ncbi_uid=&link_uid=NC_000006.12">GenBank</a> </p><div id="divNC_000006" class="SeqViewerApp" style="clear:both;" data-sv="appname=ncbi-portal-gtr&embedded=true&noslider=1&id=NC_000006.12&from=26085791&to=26099979&tracks=[key:sequence_track,name:Sequence,display_name:Sequence,category:Sequence,annots:Sequence,ShowLabel:false][key:gene_model_track,name:Genes---Unnamed,display_name:Genes,annots:Unnamed,Options:MergePairs,SNPs:false,CDSProductFeats:true,ShowLabelsForAllFeatures:true,HighlightMode:2][key:feature_track,name:Genes---other,display_name:Genes - other,subkey:ncRNA,annots:other,Layout:Adaptive][key:feature_track,name:Genes---tRNA,display_name:Genes - tRNA,subkey:tRNA,annots:tRNA,Layout:Adaptive][key:SNP_track,name:SNP,annots:SNP,Layout:Adaptive][key:SNP_Bins_track,name:Clinical Variants][key:SNP_Bins_track,name:Cited Variants][key:GWAS_track,name:GWAS Tracks,display_name:Association Results]"><a href="?appname=ncbi-portal-gtr&embedded=true&noslider=1&id=NC_000006.12&from=26085791&to=26099979&tracks=[key:sequence_track,name:Sequence,display_name:Sequence,category:Sequence,annots:Sequence,ShowLabel:false][key:gene_model_track,name:Genes---Unnamed,display_name:Genes,annots:Unnamed,Options:MergePairs,SNPs:false,CDSProductFeats:true,ShowLabelsForAllFeatures:true,HighlightMode:2][key:feature_track,name:Genes---other,display_name:Genes - other,subkey:ncRNA,annots:other,Layout:Adaptive][key:feature_track,name:Genes---tRNA,display_name:Genes - tRNA,subkey:tRNA,annots:tRNA,Layout:Adaptive][key:SNP_track,name:SNP,annots:SNP,Layout:Adaptive][key:SNP_Bins_track,name:Clinical Variants][key:SNP_Bins_track,name:Cited Variants][key:GWAS_track,name:GWAS Tracks,display_name:Association Results]"></a></div></div></div><input name="nucleotideLink_NC_000006.12" sid="1" type="hidden" id="nucleotideLink_NC_000006_12_26087428_26098342" value="<p class="note-link"><strong class="margin_r1">Go to nucleotide</strong><a title="Nucleotide Graphic report" href="/nuccore/NC_000006.12?report=graph&amp;from=26085791&amp;to=26099979&amp;content=5" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NC_000006.12">Graphics</a><a title="Nucleotide FASTA report" href="/nuccore/NC_000006.12?report=fasta&amp;from=26087429&amp;to=26098343" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NC_000006.12">FASTA</a><a title="Nucleotide GenBank report" href="/nuccore/NC_000006.12?report=genbank&amp;from=26087429&amp;to=26098343" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NC_000006.12">GenBank</a></p>" /><input name="relString_NC_000006.12" sid="1" type="hidden" id="relString_NC_000006_12_26087428_26098342" value="embedded=true&amp;noslider=1&amp;id=NC_000006.12&amp;from=26085791&amp;to=26099979&amp;content=5" /><input name="nucleotideLink_NG_008720.2" sid="1" type="hidden" id="nucleotideLink_NG_008720_2_5000_12960" value="<p class="note-link"><strong class="margin_r1">Go to nucleotide</strong><a title="Nucleotide Graphic report" href="/nuccore/NG_008720.2?report=graph&amp;from=3806&amp;to=14154&amp;content=5" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NG_008720.2">Graphics</a><a title="Nucleotide FASTA report" href="/nuccore/NG_008720.2?report=fasta&amp;from=5001&amp;to=12961" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NG_008720.2">FASTA</a><a title="Nucleotide GenBank report" href="/nuccore/NG_008720.2?report=genbank&amp;from=5001&amp;to=12961" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NG_008720.2">GenBank</a></p>" /><input name="relString_NG_008720.2" sid="1" type="hidden" id="relString_NG_008720_2_5000_12960" value="embedded=true&amp;noslider=1&amp;id=NG_008720.2&amp;from=3806&amp;to=14154&amp;content=5" /><input name="nucleotideLink_NC_060930.1" sid="1" type="hidden" id="nucleotideLink_NC_060930_1_25955570_25966490" value="<p class="note-link"><strong class="margin_r1">Go to nucleotide</strong><a title="Nucleotide Graphic report" href="/nuccore/NC_060930.1?report=graph&amp;from=25953932&amp;to=25968128&amp;content=5" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NC_060930.1">Graphics</a><a title="Nucleotide FASTA report" href="/nuccore/NC_060930.1?report=fasta&amp;from=25955571&amp;to=25966491" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NC_060930.1">FASTA</a><a title="Nucleotide GenBank report" href="/nuccore/NC_060930.1?report=genbank&amp;from=25955571&amp;to=25966491" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NC_060930.1">GenBank</a></p>" /><input name="relString_NC_060930.1" sid="1" type="hidden" id="relString_NC_060930_1_25955570_25966490" value="embedded=true&amp;noslider=1&amp;id=NC_060930.1&amp;from=25953932&amp;to=25968128&amp;content=5" /><input name="nucleotideLink_NC_000006.11" sid="1" type="hidden" id="nucleotideLink_NC_000006_11_26087656_26098570" value="<p class="note-link"><strong class="margin_r1">Go to nucleotide</strong><a title="Nucleotide Graphic report" href="/nuccore/NC_000006.11?report=graph&amp;from=26086019&amp;to=26100207&amp;content=5" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NC_000006.11">Graphics</a><a title="Nucleotide FASTA report" href="/nuccore/NC_000006.11?report=fasta&amp;from=26087657&amp;to=26098571" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NC_000006.11">FASTA</a><a title="Nucleotide GenBank report" href="/nuccore/NC_000006.11?report=genbank&amp;from=26087657&amp;to=26098571" ref="ordinalpos=1&amp;ncbi_uid=&amp;link_uid=NC_000006.11">GenBank</a></p>" /><input name="relString_NC_000006.11" sid="1" type="hidden" id="relString_NC_000006_11_26087656_26098570" value="embedded=true&amp;noslider=1&amp;id=NC_000006.11&amp;from=26086019&amp;to=26100207&amp;content=5" /></div></div><div id="variation"><h2>Variation</h2><div class="ui-ncbigrid-outer-div"><div class="ui-ncbigrid-inner-div"><table class="jig-ncbigrid" data-jigconfig=""><thead><tr><th>Resource</th><th>Links for this gene</th></tr></thead><tbody><tr><td>ClinVar</td><td><a href="/clinvar?LinkName=gene_clinvar&from_uid=3077" ref="log$=recordlinks">Variants reported to ClinVar</a></td></tr><tr><td>dbVar</td><td><a href="/dbvar?LinkName=gene_dbvar&from_uid=3077" ref="log$=recordlinks">Studies and variants</a></td></tr><tr><td>SNP</td><td><a href="https://www.ncbi.nlm.nih.gov/variation/view/?q=HFE%5bgenesymbol%5d&filters=source:dbsnp" ref="ncbi_uid=3077">Variation Viewer for HFE variants</a></td></tr><tr><td>Genome viewer</td><td><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?id=GSM923418,GSM923422,GSM923420&context=GEO&assm=GCF_000001405.25&q=HFE%5bgenesymbol%5d">Explore NCBI-annotated and select non-NCBI annotated genome assemblies</a></td></tr></tbody></table></div></div></div><div id="related-pubmed"><h2>Related articles in PubMed</h2><dl><dt><a href="/pubmed?LinkName=gene_pubmed_citedinomim&from_uid=3077" ref="ncbi_uid=3077&from=gtr_gene_related_pubmed_section" data-ga-label="pubmed_omim">PubMed-OMIM</a></dt><dd>publications in PubMed explicitly cited by the gene record in OMIM.
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</dd><dt><a href="/pubmed/clinical/?term=HFE" data-ga-label="pubmed_clinical">PubMed Clinical Queries</a></dt><dd>publications in PubMed limited specific clinical
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research.</dd><dt><a href="/pubmed/?LinkName=gene_pubmed&from_uid=3077" data-ga-label="pubmed_all_related">All related articles in PubMed</a></dt><dd>sorted by relevance are shown below. <a href="/pubmed/?LinkName=gene_pubmed&from_uid=3077" data-ga-label="pubmed_all_related">Click to see all (1000) citations.</a></dd></dl><div class="generefbl-link"><ol class="generef-link"><li><a href="/pubmed/16186539/" ref="ncbi_uid=3077&link_uid=16186539" data-ga-label="pubmed_article">Association of the H63D polymorphism in the hemochromatosis gene with sporadic ALS.</a><span class="pubmed-auth-date"><br />Goodall EF, Greenway MJ, van Marion I, Carroll CB, Hardiman O, Morrison KEGoodall EF, <em>et al</em>. Neurology, 2005 Sep 27. PMID 16186539</span></li><li><a href="/pubmed/16399493/" ref="ncbi_uid=3077&link_uid=16399493" data-ga-label="pubmed_article">HFE genotypes and dietary heme iron: no evidence of strong gene-nutrient interaction on serum ferritin concentrations in middle-aged women.</a><span class="pubmed-auth-date"><br />van der A DL, Peeters PH, Grobbee DE, Roest M, Voorbij HA, van der Schouw YTvan der A DL, <em>et al</em>. Nutr Metab Cardiovasc Dis, 2006 Jan. PMID 16399493</span></li><li><a href="/pubmed/16393683/" ref="ncbi_uid=3077&link_uid=16393683" data-ga-label="pubmed_article">Iron binding saturation and genotypic testing for hereditary hemochromatosis in patients with liver disease.</a><span class="pubmed-auth-date"><br />Nichols L, Dickson G, Phan PG, Kant JANichols L, <em>et al</em>. Am J Clin Pathol, 2006 Feb. PMID 16393683</span></li><li><a href="/pubmed/16364490/" ref="ncbi_uid=3077&link_uid=16364490" data-ga-label="pubmed_article">Effect of correcting transferrin saturation for body mass index in HFE C282Y homozygotes.</a><span class="pubmed-auth-date"><br />Waalen J, Beutler EWaalen J, <em>et al</em>. J Hepatol, 2006 Feb. PMID 16364490</span></li><li><a href="/pubmed/16337066/" ref="ncbi_uid=3077&link_uid=16337066" data-ga-label="pubmed_article">[Screening for HFE C282Y mutation at birth?].</a><span class="pubmed-auth-date"><br />Rochette J, Cadet ERochette J, <em>et al</em>. Rev Med Interne, 2006 Jan. PMID 16337066</span></li></ol></div></div></div>
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