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HFE hemochromatosis [ Homo sapiens (human) ]

Gene ID: 3077, updated on 8-Apr-2014
Official Symbol
HFEprovided by HGNC
Official Full Name
hemochromatosisprovided by HGNC
Primary source
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]
Location :
6p21.3
Sequence :
Chromosome: 6; NC_000006.12 (26087281..26096117)

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?

Associated conditions

Description Tests
Alzheimer's disease
MedGen: C0002395 OMIM: 104300 GeneReviews: Alzheimer Disease Overview
Compare labs
Familial porphyria cutanea tarda
MedGen: C0268323 OMIM: 176100 GeneReviews: Not available
Compare labs
Hereditary hemochromatosis Compare labs
Microvascular complications of diabetes 7
MedGen: CN034317 OMIM: 612635 GeneReviews: Not available
Compare labs
Transferrin serum level quantitative trait locus 2
MedGen: C3280096 OMIM: 614193 GeneReviews: Not available
Compare labs
Variegate porphyria
MedGen: C0162532 OMIM: 176200 GeneReviews: Not available
Compare labs

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
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 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
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, p27 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 Protein Interaction Database

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
antigen binding IBA
Inferred from Biological aspect of Ancestor
more info
 
peptide antigen binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
antigen processing and presentation IBA
Inferred from Biological aspect of Ancestor
more info
 
antigen processing and presentation of peptide antigen via MHC class I IEA
Inferred from Electronic Annotation
more info
 
cellular iron ion homeostasis TAS
Traceable Author Statement
more info
PubMed 
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 
multicellular organismal iron ion homeostasis IEA
Inferred from Electronic Annotation
more info
 
positive regulation of T cell mediated cytotoxicity IEA
Inferred from Electronic Annotation
more info
 
protein complex assembly TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
MHC class I protein complex IEA
Inferred from Electronic Annotation
more info
 
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 
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 
Preferred Names
hereditary hemochromatosis protein
Names
hereditary hemochromatosis protein
high Fe
MHC class I-like protein HFE
hereditary hemochromatosis protein HLA-H

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)

mRNA and Protein(s)

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

    See proteins identical to 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
    Blast Score: 307
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:27202
    Blast Score: 382
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  2. NM_139003.2NP_620572.1  hereditary hemochromatosis protein isoform 3 precursor

    See proteins identical to 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
    Blast Score: 280
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:27113
    Blast Score: 165
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  3. NM_139004.2NP_620573.1  hereditary hemochromatosis protein isoform 4 precursor

    See proteins identical to 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
    Blast Score: 307
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:27113
    Blast Score: 167
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  4. NM_139006.2NP_620575.1  hereditary hemochromatosis protein isoform 6 precursor

    See proteins identical to 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
    Blast Score: 279
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:27202
    Blast Score: 377
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  5. NM_139007.2NP_620576.1  hereditary hemochromatosis protein isoform 7 precursor

    See proteins identical to 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
    Blast Score: 307
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:27114
    Blast Score: 234
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  6. NM_139008.2NP_620577.1  hereditary hemochromatosis protein isoform 8 precursor

    See proteins identical to 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
    Blast Score: 279
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:27114
    Blast Score: 230
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  7. NM_139009.2NP_620578.1  hereditary hemochromatosis protein isoform 9 precursor

    See proteins identical to 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
    Blast Score: 304
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:23179
    Blast Score: 343
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  8. NM_139010.2NP_620579.1  hereditary hemochromatosis protein isoform 10 precursor

    See proteins identical to 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
    Blast Score: 303
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
  9. NM_139011.2NP_620580.1  hereditary hemochromatosis protein isoform 11 precursor

    See proteins identical to 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 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000006.12

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

mRNA and Protein(s)

  1. XM_006715075.1XP_006715138.1  

    Conserved Domains (2) summary
    cd07698
    Location:206298
    Blast Score: 306
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:27202
    Blast Score: 383
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2

RNA

  1. XR_241893.1 RNA Sequence

Alternate HuRef

Genomic

  1. AC_000138.1 Alternate HuRef

    Range
    26030572..26038529
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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.

Supplemental Content

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