LOCUS       NM_000410               5176 bp    mRNA    linear   PRI 05-OCT-2024
DEFINITION  Homo sapiens homeostatic iron regulator (HFE), transcript variant
            1, mRNA.
ACCESSION   NM_000410
VERSION     NM_000410.4
KEYWORDS    RefSeq; MANE 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 5176)
  AUTHORS   Li,K., Chai,D., Ren,S., Lian,X., Shi,X., Xu,Y., Bao,L., Yang,S.,
            Liang,Y., Li,X. and Du,H.
  TITLE     beta2-microglobulin induced apoptosis of tumor cells via the ERK
            signaling pathway by directly interacting with HFE in
            HER2-overexpressing breast cancer
  JOURNAL   BMC Cancer 24 (1), 991 (2024)
   PUBMED   39128984
  REMARK    GeneRIF: beta2-microglobulin induced apoptosis of tumor cells via
            the ERK signaling pathway by directly interacting with HFE in
            HER2-overexpressing breast cancer.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 5176)
  AUTHORS   Mikaeeli,S., Ben Djoudi Ouadda,A., Evagelidis,A., Essalmani,R.,
            Ramos,O.H.P., Fruchart-Gaillard,C. and Seidah,N.G.
  TITLE     Insights into PCSK9-LDLR Regulation and Trafficking via the
            Differential Functions of MHC-I Proteins HFE and HLA-C
  JOURNAL   Cells 13 (10), 857 (2024)
   PUBMED   38786080
  REMARK    GeneRIF: Insights into PCSK9-LDLR Regulation and Trafficking via
            the Differential Functions of MHC-I Proteins HFE and HLA-C.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 5176)
  AUTHORS   Mannisto,V.T., Hakkarainen,K., Jula,A., Lundqvist,A.,
            Vihervaara,T., Erlund,I. and Aberg,F.
  TITLE     Serum ferritin level is associated with liver fibrosis and incident
            liver-related outcomes independent of HFE genotype in the general
            population
  JOURNAL   Scand J Gastroenterol 59 (5), 592-599 (2024)
   PUBMED   38329447
  REMARK    GeneRIF: Serum ferritin level is associated with liver fibrosis and
            incident liver-related outcomes independent of HFE genotype in the
            general population.
REFERENCE   4  (bases 1 to 5176)
  AUTHORS   Singal,M., Mahmoud,A. and Phatak,P.D.
  TITLE     Clinical characteristics of HFE C282Y/H63D compound heterozygotes
            identified in a specialty practice: key differences from HFE C282Y
            homozygotes
  JOURNAL   Expert Rev Hematol 17 (4-5), 145-152 (2024)
   PUBMED   38551816
  REMARK    GeneRIF: Clinical characteristics of HFE C282Y/H63D compound
            heterozygotes identified in a specialty practice: key differences
            from HFE C282Y homozygotes.
REFERENCE   5  (bases 1 to 5176)
  AUTHORS   Lucas,M.R., Atkins,J.L., Pilling,L.C., Shearman,J.D. and Melzer,D.
  TITLE     HFE genotypes, haemochromatosis diagnosis and clinical outcomes at
            age 80 years: a prospective cohort study in the UK Biobank
  JOURNAL   BMJ Open 14 (3), e081926 (2024)
   PUBMED   38479735
  REMARK    GeneRIF: HFE genotypes, haemochromatosis diagnosis and clinical
            outcomes at age 80 years: a prospective cohort study in the UK
            Biobank.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 5176)
  AUTHORS   Barton,J.C. and Parker,C.J.
  TITLE     HFE-Related Hemochromatosis
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301613
REFERENCE   7  (bases 1 to 5176)
  AUTHORS   Geraghty,D.E., Koller,B.H., Pei,J. and Hansen,J.A.
  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 5176)
  AUTHORS   Dugast,I.J., Papadopoulos,P., Zappone,E., Jones,C., Theriault,K.,
            Handelman,G.J., Benarous,R. and Drysdale,J.W.
  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 5176)
  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 5176)
  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 U91328.1.
            
            On Jun 2, 2020 this sequence version replaced NM_000410.3.
            
            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. [provided by
            RefSeq, May 2022].
            
            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 :: SRR14038197.360750.1,
                                           SRR1803611.128876.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000357618.10/ ENSP00000417404.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-88                U91328.1           53543-53630         c
            89-352              U91328.1           49955-50218         c
            353-628             U91328.1           49470-49745         c
            629-904             U91328.1           48099-48374         c
            905-1018            U91328.1           47827-47940         c
            1019-5176           U91328.1           42716-46873         c
FEATURES             Location/Qualifiers
     source          1..5176
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p22.2"
     gene            1..5176
                     /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..88
                     /gene="HFE"
                     /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2"
                     /inference="alignment:Splign:2.1.0"
     CDS             13..1059
                     /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"
     exon            89..352
                     /gene="HFE"
                     /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2"
                     /inference="alignment:Splign:2.1.0"
     exon            353..628
                     /gene="HFE"
                     /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2"
                     /inference="alignment:Splign:2.1.0"
     exon            629..904
                     /gene="HFE"
                     /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2"
                     /inference="alignment:Splign:2.1.0"
     exon            905..1018
                     /gene="HFE"
                     /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1019..5176
                     /gene="HFE"
                     /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3641..3646
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HFE"
                     /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2"
                     /note="hexamer: AATAAA"
     polyA_site      3662
                     /gene="HFE"
                     /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2"
                     /note="major polyA site"
     regulatory      5153..5158
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HFE"
                     /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2"
                     /note="hexamer: ATTAAA"
     polyA_site      5176
                     /gene="HFE"
                     /gene_synonym="HFE1; HH; HLA-H; MVCD7; TFQTL2"
ORIGIN      
        1 agagctgggg aaatgggccc gcgagccagg ccggcgcttc tcctcctgat gcttttgcag
       61 accgcggtcc tgcaggggcg cttgctgcgt tcacactctc tgcactacct cttcatgggt
      121 gcctcagagc aggaccttgg tctttccttg tttgaagctt tgggctacgt ggatgaccag
      181 ctgttcgtgt tctatgatca tgagagtcgc cgtgtggagc cccgaactcc atgggtttcc
      241 agtagaattt caagccagat gtggctgcag ctgagtcaga gtctgaaagg gtgggatcac
      301 atgttcactg ttgacttctg gactattatg gaaaatcaca accacagcaa ggagtcccac
      361 accctgcagg tcatcctggg ctgtgaaatg caagaagaca acagtaccga gggctactgg
      421 aagtacgggt atgatgggca ggaccacctt gaattctgcc ctgacacact ggattggaga
      481 gcagcagaac ccagggcctg gcccaccaag ctggagtggg aaaggcacaa gattcgggcc
      541 aggcagaaca gggcctacct ggagagggac tgccctgcac agctgcagca gttgctggag
      601 ctggggagag gtgttttgga ccaacaagtg cctcctttgg tgaaggtgac acatcatgtg
      661 acctcttcag tgaccactct acggtgtcgg gccttgaact actaccccca gaacatcacc
      721 atgaagtggc tgaaggataa gcagccaatg gatgccaagg agttcgaacc taaagacgta
      781 ttgcccaatg gggatgggac ctaccagggc tggataacct tggctgtacc ccctggggaa
      841 gagcagagat atacgtgcca ggtggagcac ccaggcctgg atcagcccct cattgtgatc
      901 tgggagccct caccgtctgg caccctagtc attggagtca tcagtggaat tgctgttttt
      961 gtcgtcatct tgttcattgg aattttgttc ataatattaa ggaagaggca gggttcaaga
     1021 ggagccatgg ggcactacgt cttagctgaa cgtgagtgac acgcagcctg cagactcact
     1081 gtgggaagga gacaaaacta gagactcaaa gagggagtgc atttatgagc tcttcatgtt
     1141 tcaggagaga gttgaaccta aacatagaaa ttgcctgacg aactccttga ttttagcctt
     1201 ctctgttcat ttcctcaaaa agatttcccc atttaggttt ctgagttcct gcatgccggt
     1261 gatccctagc tgtgacctct cccctggaac tgtctctcat gaacctcaag ctgcatctag
     1321 aggcttcctt catttcctcc gtcacctcag agacatacac ctatgtcatt tcatttccta
     1381 tttttggaag aggactcctt aaatttgggg gacttacatg attcatttta acatctgaga
     1441 aaagctttga accctgggac gtggctagtc ataaccttac cagattttta cacatgtatc
     1501 tatgcatttt ctggacccgt tcaacttttc ctttgaatcc tctctctgtg ttacccagta
     1561 actcatctgt caccaagcct tggggattct tccatctgat tgtgatgtga gttgcacagc
     1621 tatgaaggct gtacactgca cgaatggaag aggcacctgt cccagaaaaa gcatcatggc
     1681 tatctgtggg tagtatgatg ggtgttttta gcaggtagga ggcaaatatc ttgaaagggg
     1741 ttgtgaagag gtgttttttc taattggcat gaaggtgtca tacagatttg caaagtttaa
     1801 tggtgccttc atttgggatg ctactctagt attccagacc tgaagaatca caataatttt
     1861 ctacctggtc tctccttgtt ctgataatga aaattatgat aaggatgata aaagcactta
     1921 cttcgtgtcc gactcttctg agcacctact tacatgcatt actgcatgca cttcttacaa
     1981 taattctatg agataggtac tattatcccc atttcttttt taaatgaaga aagtgaagta
     2041 ggccgggcac ggtggctcac gcctgtaatc ccagcacttt gggaggccaa agcgggtgga
     2101 tcacgaggtc aggagatcga gaccatcctg gctaacatgg tgaaacccca tctctaataa
     2161 aaatacaaaa aattagctgg gcgtggtggc agacgcctgt agtcccagct actcggaagg
     2221 ctgaggcagg agaatggcat gaacccagga ggcagagctt gcagtgagcc gagtttgcgc
     2281 cactgcactc cagcctaggt gacagagtga gactccatct caaaaaaata aaaataaaaa
     2341 taaaaaaatg aaaaaaaaaa gaaagtgaag tatagagtat ctcatagttt gtcagtgata
     2401 gaaacaggtt tcaaactcag tcaatctgac cgtttgatac atctcagaca ccactacatt
     2461 cagtagttta gatgcctaga ataaatagag aaggaaggag atggctcttc tcttgtctca
     2521 ttgtgtttct tctgagtgag cttgaatcac atgaagggga acagcagaaa acaaccaact
     2581 gatcctcagc tgtcatgttt cctttaaaag tccctgaagg aaggtcctgg aatgtgactc
     2641 ccttgctcct ctgttgctct ctttggcatt catttctttg gaccctacgc aaggactgta
     2701 attggtgggg acagctagtg gccctgctgg gcttcacaca cggtgtcctc cctaggccag
     2761 tgcctctgga gtcagaactc tggtggtatt tccctcaatg aagtggagta agctctctca
     2821 ttttgagatg gtataatgga agccaccaag tggcttagag gatgcccagg tccttccatg
     2881 gagccactgg ggttccggtg cacattaaaa aaaaaatcta accaggacat tcaggaattg
     2941 ctagattctg ggaaatcagt tcaccatgtt caaaagagtc tttttttttt ttttgagact
     3001 ctattgccca ggctggagtg caatggcatg atctcggctc actgtaacct ctgcctccca
     3061 ggttcaagcg attctcctgt ctcagcctcc caagtagctg ggattacagg cgtgcaccac
     3121 catgcccggc taatttttgt atttttagta gagacagggt ttcaccatgt tggccaggct
     3181 ggtctcgaac tctcctgacc tcgtgatccg cctgcctcgg cctcccaaag tgctgagatt
     3241 acaggtgtga gccaccctgc ccagccgtca aaagagtctt aatatatata tccagatggc
     3301 atgtgtttac tttatgttac tacatgcact tggctgcata aatgtggtac aagcattctg
     3361 tcttgaaggg caggtgcttc aggataccat atacagctca gaagtttctt ctttaggcat
     3421 taaattttag caaagatatc tcatctcttc ttttaaacca ttttcttttt ttgtggttag
     3481 aaaagttatg tagaaaaaag taaatgtgat ttacgctcat tgtagaaaag ctataaaatg
     3541 aatacaatta aagctgttat ttaattagcc agtgaaaaac tattaacaac ttgtctatta
     3601 cctgttagta ttattgttgc attaaaaatg catatacttt aataaatgta tattgtattg
     3661 tatactgcat gattttattg aagttcttgt tcatcttgtg tatatactta atcgctttgt
     3721 cattttggag acatttattt tgcttctaat ttctttacat tttgtcttac ggaatatttt
     3781 cattcaactg tggtagccga attaatcgtg tttcttcact ctagggacat tgtcgtctaa
     3841 gttgtaagac attggttatt ttaccagcaa accattctga aagcatatga caaattattt
     3901 ctctcttaat atcttactat actgaaagca gactgctata aggcttcact tactcttcta
     3961 cctcataagg aatatgttac aattaattta ttaggtaagc atttgtttta tattggtttt
     4021 atttcacctg ggctgagatt tcaagaaaca ccccagtctt cacagtaaca catttcacta
     4081 acacatttac taaacatcag caactgtggc ctgttaattt ttttaataga aattttaagt
     4141 cctcattttc tttcggtgtt ttttaagctt aatttttctg gctttattca taaattctta
     4201 aggtcaacta catttgaaaa atcaaagacc tgcattttaa attcttattc acctctggca
     4261 aaaccattca caaaccatgg tagtaaagag aagggtgaca cctggtggcc ataggtaaat
     4321 gtaccacggt ggtccggtga ccagagatgc agcgctgagg gttttcctga aggtaaagga
     4381 ataaagaatg ggtggagggg cgtgcactgg aaatcacttg tagagaaaag cccctgaaaa
     4441 tttgagaaaa caaacaagaa actacttacc agctatttga attgctggaa tcacaggcca
     4501 ttgctgagct gcctgaactg ggaacacaac agaaggaaaa caaaccactc tgataatcat
     4561 tgagtcaagt acagcaggtg attgaggact gctgagaggt acaggccaaa attcttatgt
     4621 tgtattataa taatgtcatc ttataatact gtcagtattt tataaaacat tcttcacaaa
     4681 ctcacacaca tttaaaaaca aaacactgtc tctaaaatcc ccaaattttt cataaactca
     4741 gttttaaact aacttttttt caaaccacaa tctgatttaa caatgactat catttaaata
     4801 tttctgactt tcaaattaaa gattttcaca tgcaggctga tatttgtaat tgtgattctc
     4861 tctgtaggct ttgggtataa tgtgttcttt tccttttttg catcagcgat taacttctac
     4921 actctaacat gtagaatgtt actacaatat taaagtattt tgtatgacaa ttttatttga
     4981 aagcctagga tgcgttgaca tcctgcatgc atttattact tgatatgcat gcattctggt
     5041 atctcaagca ttctatttct gagtaattgt ttaaggtgta gaagagatag atatggtgga
     5101 tttggagttg atacttatat attttctatt tcttggatgg atgaatttgt acattaaaag
     5161 ttttccatgg cagaaa
//
