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    HFE hemochromatosis [ Homo sapiens (human) ]

    Gene ID: 3077, updated on 28-Jun-2015
    Official Symbol
    HFEprovided by HGNC
    Official Full Name
    hemochromatosisprovided by HGNC
    Primary source
    HGNC:HGNC:4886
    See related
    Ensembl:ENSG00000010704; HPRD:01993; MIM:613609; Vega:OTTHUMG00000016348
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HH; HFE1; HLA-H; MVCD7; TFQTL2
    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]
    Orthologs
    Location:
    6p21.3
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    107 current GRCh38.p2 (GCF_000001405.28) 6 NC_000006.12 (26087281..26096117)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (26087422..26096438)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene histone cluster 1, H3c Neighboring gene histone cluster 1, H1c Neighboring gene histone cluster 1, H4c Neighboring gene histone cluster 1, H1t

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    NHGRI GWAS Catalog

    Description
    A genome-wide association study of red blood cell traits using the electronic medical record.
    NHGRI GWA Catalog
    A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.
    NHGRI GWA Catalog
    Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations.
    NHGRI GWA Catalog
    Biological, clinical and population relevance of 95 loci for blood lipids.
    NHGRI GWA Catalog
    Common variants at 10 genomic loci influence hemoglobin A₁(C) levels via glycemic and nonglycemic pathways.
    NHGRI GWA Catalog
    Common variants in TMPRSS6 are associated with iron status and erythrocyte volume.
    NHGRI GWA Catalog
    Discovery and refinement of loci associated with lipid levels.
    NHGRI GWA Catalog
    Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits.
    NHGRI GWA Catalog
    Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
    NHGRI GWA Catalog
    Genome-wide admixture and association study of serum iron, ferritin, transferrin saturation and total iron binding capacity in African Americans.
    NHGRI GWA Catalog
    Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network.
    NHGRI GWA Catalog
    Genome-wide association study identifies genetic loci associated with iron deficiency.
    NHGRI GWA Catalog
    Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
    NHGRI GWA Catalog
    Genome-wide association study identifies two loci strongly affecting transferrin glycosylation.
    NHGRI GWA Catalog
    Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels.
    NHGRI GWA Catalog
    Genome-wide association study of hematological and biochemical traits in a Japanese population.
    NHGRI GWA Catalog
    GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.
    NHGRI GWA Catalog
    Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels.
    NHGRI GWA Catalog
    Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
    NHGRI GWA Catalog
    Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels.
    NHGRI GWA Catalog
    Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis.
    NHGRI GWA Catalog
    Sequence variants in three loci influence monocyte counts and erythrocyte volume.
    NHGRI GWA Catalog
    Seventy-five genetic loci influencing the human red blood cell.
    NHGRI GWA Catalog
    Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels.
    NHGRI GWA Catalog

    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef Myristoylation of HIV-1 Nef at position 2 and the PxxP proline-rich motif of Nef at positions 62-65 are required for Nef-induced downregulation of HFE; amino acid residue Y282 in HFE is involved in the downregulation by Nef PubMed
    nef HIV-1 Nef downregulates the macrophage-expressed MHC 1b protein HFE by rerouting HFE to a perinuclear structure that overlaps the trans-Golgi network, causing a 90% reduction of surface HFE PubMed

    Go to the HIV-1, Human Interaction Database

    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • MGC103790, MGC:150812, dJ221C16.10.1, IMAGE:40125754

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    beta-2-microglobulin binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    co-receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    NOT peptide antigen binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    NOT peptide antigen binding IKR
    Inferred from Key Residues
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    transferrin receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    BMP signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acute-phase response IEA
    Inferred from Electronic Annotation
    more info
     
    NOT antigen processing and presentation IC
    Inferred by Curator
    more info
    PubMed 
    NOT antigen processing and presentation of peptide antigen via MHC class I IKR
    Inferred from Key Residues
    more info
    PubMed 
    cellular iron ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to iron ion starvation IEA
    Inferred from Electronic Annotation
    more info
     
    female pregnancy IEA
    Inferred from Electronic Annotation
    more info
     
    hormone biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    immune response IEA
    Inferred from Electronic Annotation
    more info
     
    iron ion import into cell IDA
    Inferred from Direct Assay
    more info
    PubMed 
    liver regeneration IEA
    Inferred from Electronic Annotation
    more info
     
    multicellular organismal iron ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of CD8-positive, alpha-beta T cell activation IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    negative regulation of T cell antigen processing and presentation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of T cell cytokine production IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    negative regulation of proteasomal ubiquitin-dependent protein catabolic process IC
    Inferred by Curator
    more info
    PubMed 
    negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of receptor binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of pathway-restricted SMAD protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein complex assembly TAS
    Traceable Author Statement
    more info
    PubMed 
    response to iron ion starvation IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    HFE-transferrin receptor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    NOT MHC class I protein complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    NOT MHC class I protein complex IKR
    Inferred from Key Residues
    more info
    PubMed 
    apical part of cell IDA
    Inferred from Direct Assay
    more info
    PubMed 
    basal part of cell IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytoplasmic vesicle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    early endosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    external side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    integral component of plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    recycling endosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    terminal web IEA
    Inferred from Electronic Annotation
    more info
     
    Preferred Names
    hereditary hemochromatosis protein
    Names
    hereditary hemochromatosis protein
    MHC class I-like protein HFE
    hereditary hemochromatosis protein HLA-H
    high Fe

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008720.2 RefSeqGene

      Range
      5001..12961
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_748

    mRNA and Protein(s)

    1. NM_000410.3NP_000401.1  hereditary hemochromatosis protein isoform 1 precursor

      See identical proteins and their annotated locations for NP_000401.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform.
      Source sequence(s)
      AF115265, AJ249337, U91328
      Consensus CDS
      CCDS4578.1
      UniProtKB/Swiss-Prot
      Q30201
      Conserved Domains (2) summary
      cd07698
      Location:206298
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:27202
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    2. NM_001300749.1NP_001287678.1  hereditary hemochromatosis protein isoform 12 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (12) uses an alternate splice acceptor site at its 3'-terminal exon, compared to variant 1. This variant encodes isoform 12 which has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AJ249337, AJ298840, AK300933, BC117201
      Consensus CDS
      CCDS75412.1
      UniProtKB/TrEMBL
      B4DV50
      UniProtKB/TrEMBL
      F8W7W8
      UniProtKB/Swiss-Prot
      Q30201
      Conserved Domains (2) summary
      cd07698
      Location:206298
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:27202
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    3. NM_139003.2NP_620572.1  hereditary hemochromatosis protein isoform 3 precursor

      See identical proteins and their annotated locations for NP_620572.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an internal in-frame segment of the coding region, as compared to variant 1, resulting in a shorter protein (isoform 3).
      Source sequence(s)
      AF149804, AJ249335, U91328
      Consensus CDS
      CCDS47386.1
      UniProtKB/Swiss-Prot
      Q30201
      Conserved Domains (2) summary
      cd07698
      Location:110192
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:27113
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    4. NM_139004.2NP_620573.1  hereditary hemochromatosis protein isoform 4 precursor

      See identical proteins and their annotated locations for NP_620573.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an internal in-frame segment of the coding region, compared to variant 1, resulting in a shorter protein (isoform 4).
      Source sequence(s)
      AJ249337, U91328
      Consensus CDS
      CCDS4579.1
      UniProtKB/Swiss-Prot
      Q30201
      Related
      ENSP00000313776, OTTHUMP00000215790, ENST00000317896, OTTHUMT00000356137
      Conserved Domains (2) summary
      cd07698
      Location:114206
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:27113
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    5. NM_139006.2NP_620575.1  hereditary hemochromatosis protein isoform 6 precursor

      See identical proteins and their annotated locations for NP_620575.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks an internal in-frame segment of the coding region, as compared to variant 1, resulting in a shorter protein (isoform 6).
      Source sequence(s)
      AF079407, AJ249335, U91328
      Consensus CDS
      CCDS54974.1
      UniProtKB/Swiss-Prot
      Q30201
      Conserved Domains (2) summary
      cd07698
      Location:207284
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:27202
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    6. NM_139007.2NP_620576.1  hereditary hemochromatosis protein isoform 7 precursor

      See identical proteins and their annotated locations for NP_620576.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) lacks an internal in-frame segment of the coding region, as compared to variant 1, resulting in a shorter protein isoform (7).
      Source sequence(s)
      AJ249336, U91328
      Consensus CDS
      CCDS4580.1
      UniProtKB/Swiss-Prot
      Q30201
      Related
      ENSP00000259699, OTTHUMP00000215788, ENST00000349999, OTTHUMT00000356135
      Conserved Domains (2) summary
      cd07698
      Location:118210
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:27114
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    7. NM_139008.2NP_620577.1  hereditary hemochromatosis protein isoform 8 precursor

      See identical proteins and their annotated locations for NP_620577.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) lacks two internal in-frame segments of the coding region, as compared to variant 1, resulting in a shorter protein (isoform 8).
      Source sequence(s)
      AF079409, AJ249335, U91328
      Consensus CDS
      CCDS54975.1
      UniProtKB/Swiss-Prot
      Q30201
      Conserved Domains (2) summary
      cd07698
      Location:119196
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:27114
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    8. NM_139009.2NP_620578.1  hereditary hemochromatosis protein isoform 9 precursor

      See identical proteins and their annotated locations for NP_620578.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) lacks an internal in-frame segment of the coding region through the use of an alternate splice acceptor site, as compared to variant 1, resulting in a shorter protein (isoform 9).
      Source sequence(s)
      AJ249335, U91328
      Consensus CDS
      CCDS47387.1
      UniProtKB/Swiss-Prot
      Q30201
      Conserved Domains (2) summary
      cd07698
      Location:183275
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:23179
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    9. NM_139010.2NP_620579.1  hereditary hemochromatosis protein isoform 10 precursor

      See identical proteins and their annotated locations for NP_620579.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10) lacks an internal in-frame segment of the coding region, as compared to variant 1, resulting in a shorter protein (isoform 10).
      Source sequence(s)
      AJ250635, U91328
      Consensus CDS
      CCDS4581.1
      UniProtKB/Swiss-Prot
      Q30201
      Conserved Domains (1) summary
      cd07698
      Location:27118
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    10. NM_139011.2NP_620580.1  hereditary hemochromatosis protein isoform 11 precursor

      See identical proteins and their annotated locations for NP_620580.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (11) lacks a large internal part of the coding region but the reading frame is maintained, as compared to variant 1. The protein encoded is the shortest isoform (11).
      Source sequence(s)
      AJ249338, U91328
      Consensus CDS
      CCDS4582.1
      UniProtKB/Swiss-Prot
      Q30201

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p2 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p2 Primary Assembly

      Range
      26087281..26096117
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011514544.1XP_011512846.1  

      See identical proteins and their annotated locations for XP_011512846.1

      Conserved Domains (2) summary
      cd07698
      Location:210295
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:27202
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    2. XM_011514543.1XP_011512845.1  

      Conserved Domains (2) summary
      cd07698
      Location:206298
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:27202
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2

    RNA

    1. XR_241893.2 RNA Sequence

    Alternate CHM1_1.1

    Genomic

    1. NC_018917.2 Alternate CHM1_1.1

      Range
      26089764..26097723
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_139002.2: Suppressed sequence

      Description
      NM_139002.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    2. NM_139005.2: Suppressed sequence

      Description
      NM_139005.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.