LOCUS NM_000410 2222 bp mRNA linear PRI 05-NOV-2019 DEFINITION Homo sapiens homeostatic iron regulator (HFE), transcript variant 1, mRNA. ACCESSION NM_000410 VERSION NM_000410.3 KEYWORDS RefSeq; RefSeq Select. SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 2222) AUTHORS Schonfeld EA and Brown RS Jr. TITLE Genetic Causes of Liver Disease: When to Suspect a Genetic Etiology, Initial Lab Testing, and the Basics of Management JOURNAL Med. Clin. North Am. 103 (6), 991-1003 (2019) PUBMED 31582009 REMARK GeneRIF: Most (80%-90%) cases of Hereditary Hemochromatosis are caused by an autosomal recessive mutation in the HFE gene; specifically, the most common genetic mutation is homozygosity for C282Y.Two less common mutations are H63D and S65C, which usually only cause signs and symptoms of iron overload when present as compound heterozygotes with C282Y. Review article REFERENCE 2 (bases 1 to 2222) AUTHORS Paganini J, Abi-Rached L, Gouret P, Pontarotti P, Chiaroni J and Di Cristofaro J. TITLE HLAIb worldwide genetic diversity: New HLA-H alleles and haplotype structure description JOURNAL Mol. Immunol. 112, 40-50 (2019) PUBMED 31078115 REMARK GeneRIF: The high LD between HLA-H and -A. REFERENCE 3 (bases 1 to 2222) AUTHORS Allen A, Premawardhena A, Allen S, Rodrigo R, Manamperi A, Perera L, Wray K, Armitage A, Fisher C, Drakesmith A, Robson K and Weatherall D. TITLE The p.H63D allele of the HFE gene protects against low iron stores in Sri Lanka JOURNAL Blood Cells Mol. Dis. 76, 72-77 (2019) PUBMED 30827762 REMARK GeneRIF: findings suggest that selective pressure by mild iron deficiency contributes to the high frequencies of the p.H63D variant. REFERENCE 4 (bases 1 to 2222) AUTHORS Dopsaj V, Topic A, Savkovic M, Milinkovic N, Novakovic I, Cujic D and Simic-Ogrizovic S. TITLE Associations of Common Variants in HFE and TMPRSS6 Genes with Hepcidin-25 and Iron Status Parameters in Patients with End-Stage Renal Disease JOURNAL Dis. Markers 2019, 4864370 (2019) PUBMED 30984307 REMARK GeneRIF: HFE SNPs (C282Y and H63D) affect serum hepcidin-25 levels and iron status parameters in patients with end-stage renal disease. Publication Status: Online-Only REFERENCE 5 (bases 1 to 2222) AUTHORS Chen CJ, Lin TY, Wang CL, Ho CK, Chuang HY and Yu HS. TITLE Interactive Effects between Chronic Lead Exposure and the Homeostatic Iron Regulator Transport HFE Polymorphism on the Human Red Blood Cell Mean Corpuscular Volume (MCV) JOURNAL Int J Environ Res Public Health 16 (3), E354 (2019) PUBMED 30691187 REMARK GeneRIF: The aim of our study was to investigate whether the HFE genotype modifies the blood lead levels that affect the distributions of serum iron and other red blood cell indices Publication Status: Online-Only REFERENCE 6 (bases 1 to 2222) AUTHORS Barton,J.C. and Edwards,C.Q. TITLE HFE Hemochromatosis JOURNAL (in) Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K and Amemiya A (Eds.); GENEREVIEWS((R)); (1993) PUBMED 20301613 REFERENCE 7 (bases 1 to 2222) AUTHORS Geraghty DE, Koller BH, Pei J and Hansen JA. TITLE Examination of four HLA class I pseudogenes. Common events in the evolution of HLA genes and pseudogenes JOURNAL J. Immunol. 149 (6), 1947-1956 (1992) PUBMED 1517564 REFERENCE 8 (bases 1 to 2222) AUTHORS Dugast IJ, Papadopoulos P, Zappone E, Jones C, Theriault K, Handelman GJ, Benarous R and Drysdale JW. TITLE Identification of two human ferritin H genes on the short arm of chromosome 6 JOURNAL Genomics 6 (2), 204-211 (1990) PUBMED 2307464 REFERENCE 9 (bases 1 to 2222) AUTHORS Walsh,C.H. and Malins,J.M. TITLE Proliferative retinopathy in a patient with diabetes mellitus and idiopathic haemochromatosis JOURNAL Br Med J 2 (6129), 16-17 (1978) PUBMED 678784 REFERENCE 10 (bases 1 to 2222) AUTHORS Markert,R. TITLE [Biochemical studies and biopsy examination in the evaluation of liver function in cholelithiasis] JOURNAL Pol Tyg Lek 32 (27), 1041-1042 (1977) PUBMED 896549 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AJ249337.1, AF115265.1 and U91328.1. This sequence is a reference standard in the RefSeqGene project. On Apr 10, 2006 this sequence version replaced NM_000410.2. Summary: 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. At least nine alternatively spliced variants have been described for this gene. Additional variants have been found but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]. Transcript Variant: This variant (1) encodes the longest isoform. CCDS Note: This CCDS ID represents the longest isoform encoded by the HFE gene. This isoform contains both a Class I Histocompatibility antigen (MHC_I) and an Immunoglobulin constant region (IGc) domain. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1803616.105052.1, SRR1660807.164609.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END## COMPLETENESS: complete on the 3' end. PRIMARY REFSEQ_SPAN PRIMARY_IDENTIFIER PRIMARY_SPAN COMP 1-149 AJ249337.1 1-149 150-1338 AF115265.1 1-1189 1339-2222 U91328.1 45818-46701 c FEATURES Location/Qualifiers source 1..2222 /organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon:9606" /chromosome="6" /map="6p22.2" gene 1..2222 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /note="homeostatic iron regulator" /db_xref="GeneID:3077" /db_xref="HGNC:HGNC:4886" /db_xref="MIM:613609" exon 1..236 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /inference="alignment:Splign:2.1.0" misc_feature 131..133 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /note="upstream in-frame stop codon" CDS 161..1207 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /note="isoform 1 precursor is encoded by transcript variant 1; high Fe; MHC class I-like protein HFE; hereditary hemochromatosis protein HLA-H" /codon_start=1 /product="hereditary hemochromatosis protein isoform 1 precursor" /protein_id="NP_000401.1" /db_xref="CCDS:CCDS4578.1" /db_xref="GeneID:3077" /db_xref="HGNC:HGNC:4886" /db_xref="MIM:613609" /translation="MGPRARPALLLLMLLQTAVLQGRLLRSHSLHYLFMGASEQDLGL SLFEALGYVDDQLFVFYDHESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDF WTIMENHNHSKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDHLEFCPDTLDWRAAEP RAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVTS SVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGE EQRYTCQVEHPGLDQPLIVIWEPSPSGTLVIGVISGIAVFVVILFIGILFIILRKRQG SRGAMGHYVLAERE" sig_peptide 161..226 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /inference="COORDINATES: ab initio prediction:SignalP:4.0" mat_peptide 227..1204 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /product="hereditary hemochromatosis protein isoform 1" misc_feature 227..502 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q30201.1); Region: Alpha-1" misc_feature 488..490 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /experiment="experimental evidence, no additional details recorded" /note="N-linked (GlcNAc...) asparagine. {ECO:0000255}; propagated from UniProtKB/Swiss-Prot (Q30201.1); glycosylation site" misc_feature 503..775 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q30201.1); Region: Alpha-2" misc_feature 548..550 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /experiment="experimental evidence, no additional details recorded" /note="N-linked (GlcNAc...) asparagine. {ECO:0000255}; propagated from UniProtKB/Swiss-Prot (Q30201.1); glycosylation site" misc_feature 776..1051 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q30201.1); Region: Alpha-3" misc_feature 860..862 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /experiment="experimental evidence, no additional details recorded" /note="N-linked (GlcNAc...) asparagine. {ECO:0000255}; propagated from UniProtKB/Swiss-Prot (Q30201.1); glycosylation site" misc_feature 1052..1078 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q30201.1); Region: Connecting peptide" misc_feature 1079..1150 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (Q30201.1); transmembrane region" exon 237..500 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /inference="alignment:Splign:2.1.0" exon 501..776 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /inference="alignment:Splign:2.1.0" exon 777..1052 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /inference="alignment:Splign:2.1.0" exon 1053..1166 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /inference="alignment:Splign:2.1.0" exon 1167..2222 /gene="HFE" /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2" /inference="alignment:Splign:2.1.0" ORIGIN 1 ctaaagttct gaaagacctg ttgcttttca ccaggaagtt ttactgggca tctcctgagc 61 ctaggcaata gctgtagggt gacttctgga gccatccccg tttccccgcc ccccaaaaga 121 agcggagatt taacggggac gtgcggccag agctggggaa atgggcccgc gagccaggcc 181 ggcgcttctc ctcctgatgc ttttgcagac cgcggtcctg caggggcgct tgctgcgttc 241 acactctctg cactacctct tcatgggtgc ctcagagcag gaccttggtc tttccttgtt 301 tgaagctttg ggctacgtgg atgaccagct gttcgtgttc tatgatcatg agagtcgccg 361 tgtggagccc cgaactccat gggtttccag tagaatttca agccagatgt ggctgcagct 421 gagtcagagt ctgaaagggt gggatcacat gttcactgtt gacttctgga ctattatgga 481 aaatcacaac cacagcaagg agtcccacac cctgcaggtc atcctgggct gtgaaatgca 541 agaagacaac agtaccgagg gctactggaa gtacgggtat gatgggcagg accaccttga 601 attctgccct gacacactgg attggagagc agcagaaccc agggcctggc ccaccaagct 661 ggagtgggaa aggcacaaga ttcgggccag gcagaacagg gcctacctgg agagggactg 721 ccctgcacag ctgcagcagt tgctggagct ggggagaggt gttttggacc aacaagtgcc 781 tcctttggtg aaggtgacac atcatgtgac ctcttcagtg accactctac ggtgtcgggc 841 cttgaactac tacccccaga acatcaccat gaagtggctg aaggataagc agccaatgga 901 tgccaaggag ttcgaaccta aagacgtatt gcccaatggg gatgggacct accagggctg 961 gataaccttg gctgtacccc ctggggaaga gcagagatat acgtgccagg tggagcaccc 1021 aggcctggat cagcccctca ttgtgatctg ggagccctca ccgtctggca ccctagtcat 1081 tggagtcatc agtggaattg ctgtttttgt cgtcatcttg ttcattggaa ttttgttcat 1141 aatattaagg aagaggcagg gttcaagagg agccatgggg cactacgtct tagctgaacg 1201 tgagtgacac gcagcctgca gactcactgt gggaaggaga caaaactaga gactcaaaga 1261 gggagtgcat ttatgagctc ttcatgtttc aggagagagt tgaacctaaa catagaaatt 1321 gcctgacgaa ctccttgatt ttagccttct ctgttcattt cctcaaaaag atttccccat 1381 ttaggtttct gagttcctgc atgccggtga tccctagctg tgacctctcc cctggaactg 1441 tctctcatga acctcaagct gcatctagag gcttccttca tttcctccgt cacctcagag 1501 acatacacct atgtcatttc atttcctatt tttggaagag gactccttaa atttggggga 1561 cttacatgat tcattttaac atctgagaaa agctttgaac cctgggacgt ggctagtcat 1621 aaccttacca gatttttaca catgtatcta tgcattttct ggacccgttc aacttttcct 1681 ttgaatcctc tctctgtgtt acccagtaac tcatctgtca ccaagccttg gggattcttc 1741 catctgattg tgatgtgagt tgcacagcta tgaaggctgt acactgcacg aatggaagag 1801 gcacctgtcc cagaaaaagc atcatggcta tctgtgggta gtatgatggg tgtttttagc 1861 aggtaggagg caaatatctt gaaaggggtt gtgaagaggt gttttttcta attggcatga 1921 aggtgtcata cagatttgca aagtttaatg gtgccttcat ttgggatgct actctagtat 1981 tccagacctg aagaatcaca ataattttct acctggtctc tccttgttct gataatgaaa 2041 attatgataa ggatgataaa agcacttact tcgtgtccga ctcttctgag cacctactta 2101 catgcattac tgcatgcact tcttacaata attctatgag ataggtacta ttatccccat 2161 ttctttttta aatgaagaaa gtgaagtagg ccgggcacgg tggctcacgc ctgtaatccc 2221 ag //