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HFE homeostatic iron regulator [ Homo sapiens (human) ]

Gene ID: 3077, updated on 25-Nov-2021

Summary

Official Symbol
HFEprovided by HGNC
Official Full Name
homeostatic iron regulatorprovided by HGNC
Primary source
HGNC:HGNC:4886
See related
Ensembl:ENSG00000010704 MIM:613609
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]
Expression
Ubiquitous expression in thyroid (RPKM 5.0), gall bladder (RPKM 4.6) and 24 other tissues See more
Orthologs
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Genomic context

See HFE in Genome Data Viewer
Location:
6p22.2
Exon count:
7
Annotation release Status Assembly Chr Location
109.20211119 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (26087347..26098343)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (26087657..26098571)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene H3 clustered histone 3 Neighboring gene H1.2 linker histone, cluster member Neighboring gene HFE antisense RNA 1 Neighboring gene H4 clustered histone 3 Neighboring gene H1.6 linker histone, cluster member

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
A genome-wide association study of red blood cell traits using the electronic medical record.
GeneReviews: Not available
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.
GeneReviews: Not available
Alzheimer disease
MedGen: C0002395 OMIM: 104300 GeneReviews: Alzheimer Disease Overview
Compare labs
Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations.
GeneReviews: Not available
Biological, clinical and population relevance of 95 loci for blood lipids.
GeneReviews: Not available
Common variants at 10 genomic loci influence hemoglobin A₁(C) levels via glycemic and nonglycemic pathways.
GeneReviews: Not available
Common variants in TMPRSS6 are associated with iron status and erythrocyte volume.
GeneReviews: Not available
Discovery and refinement of loci associated with lipid levels.
GeneReviews: Not available
Familial porphyria cutanea tarda Compare labs
Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits.
GeneReviews: Not available
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
GeneReviews: Not available
Genome-wide admixture and association study of serum iron, ferritin, transferrin saturation and total iron binding capacity in African Americans.
GeneReviews: Not available
Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network.
GeneReviews: Not available
Genome-wide association study identifies genetic loci associated with iron deficiency.
GeneReviews: Not available
Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
GeneReviews: Not available
Genome-wide association study identifies two loci strongly affecting transferrin glycosylation.
GeneReviews: Not available
Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels.
GeneReviews: Not available
Genome-wide association study of hematological and biochemical traits in a Japanese population.
GeneReviews: Not available
GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.
GeneReviews: Not available
Hemochromatosis type 1
MedGen: C3469186 OMIM: 235200 GeneReviews: HFE Hemochromatosis
Compare labs
Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels.
GeneReviews: Not available
Microvascular complications of diabetes 7
MedGen: C2673520 OMIM: 612635 GeneReviews: Not available
Compare labs
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
GeneReviews: Not available
Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels.
GeneReviews: Not available
Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis.
GeneReviews: Not available
Sequence variants in three loci influence monocyte counts and erythrocyte volume.
GeneReviews: Not available
Seventy-five genetic loci influencing the human red blood cell.
GeneReviews: Not available
Transferrin serum level quantitative trait locus 2
MedGen: C3280096 OMIM: 614193 GeneReviews: Not available
Compare labs
Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels.
GeneReviews: Not available
Variegate porphyria
MedGen: C0162532 OMIM: 176200 GeneReviews: Variegate Porphyria
Compare labs

HIV-1 interactions

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables beta-2-microglobulin binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables co-receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
NOT enables peptide antigen binding IDA
Inferred from Direct Assay
more info
PubMed 
NOT enables peptide antigen binding IKR
Inferred from Key Residues
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables signaling receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables transferrin receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables transferrin receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
involved_in BMP signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
NOT involved_in antigen processing and presentation IC
Inferred by Curator
more info
PubMed 
NOT involved_in antigen processing and presentation of peptide antigen via MHC class I IKR
Inferred from Key Residues
more info
PubMed 
involved_in cellular iron ion homeostasis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in cellular response to iron ion IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in hormone biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
involved_in iron ion homeostasis IC
Inferred by Curator
more info
PubMed 
involved_in iron ion homeostasis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in iron ion import across plasma membrane IEA
Inferred from Electronic Annotation
more info
 
involved_in multicellular organismal iron ion homeostasis IEA
Inferred from Electronic Annotation
more info
 
involved_in negative regulation of CD8-positive, alpha-beta T cell activation IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in negative regulation of T cell antigen processing and presentation IEA
Inferred from Electronic Annotation
more info
 
involved_in negative regulation of T cell cytokine production IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in negative regulation of proteasomal ubiquitin-dependent protein catabolic process IC
Inferred by Curator
more info
PubMed 
involved_in negative regulation of receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of signaling receptor activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of ferrous iron binding IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in positive regulation of gene expression ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in positive regulation of pathway-restricted SMAD protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of peptide hormone secretion IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of protein binding IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in positive regulation of receptor binding IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in positive regulation of receptor-mediated endocytosis IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in positive regulation of signaling receptor activity IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in positive regulation of transferrin receptor binding IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in protein-containing complex assembly TAS
Traceable Author Statement
more info
PubMed 
involved_in regulation of iron ion transport IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in regulation of iron ion transport IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in regulation of protein localization to cell surface IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in response to iron ion IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in response to iron ion starvation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Component Evidence Code Pubs
part_of HFE-transferrin receptor complex IDA
Inferred from Direct Assay
more info
PubMed 
NOT part_of MHC class I protein complex IDA
Inferred from Direct Assay
more info
PubMed 
NOT part_of MHC class I protein complex IKR
Inferred from Key Residues
more info
PubMed 
located_in apical part of cell IDA
Inferred from Direct Assay
more info
PubMed 
located_in basal part of cell IDA
Inferred from Direct Assay
more info
PubMed 
located_in cytoplasmic vesicle IDA
Inferred from Direct Assay
more info
PubMed 
located_in early endosome IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in external side of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in external side of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
located_in integral component of plasma membrane TAS
Traceable Author Statement
more info
PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
 
located_in perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 
located_in plasma membrane TAS
Traceable Author Statement
more info
 
located_in recycling endosome IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
hereditary hemochromatosis protein
Names
MHC class I-like protein HFE
hereditary hemochromatosis protein HLA-H
high Fe

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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_000410.4NP_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)
    U91328
    Consensus CDS
    CCDS4578.1
    UniProtKB/Swiss-Prot
    Q30201
    Related
    ENSP00000417404.1, ENST00000357618.10
    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_001300749.2NP_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/Swiss-Prot
    Q30201
    UniProtKB/TrEMBL
    B4DV50, F8W7W8
    Related
    ENSP00000311698.6, ENST00000309234.10
    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_001384164.1NP_001371093.1  hereditary hemochromatosis protein isoform 13 precursor

    Status: REVIEWED

    Source sequence(s)
    U91328
    Conserved Domains (2) summary
    cd21021
    Location:204297
    IgC1_MHC_Ib_HLA-H; Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H; member of the C1-set of Ig superfamily (IgSF) domains
    cl08246
    Location:27202
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  4. NM_139003.3NP_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
    Related
    ENSP00000337819.8, ENST00000336625.12
    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
  5. NM_139004.3NP_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
    ENSP00000313776.7, ENST00000317896.11
    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
  6. NM_139006.3NP_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, U91328
    Consensus CDS
    CCDS54974.1
    UniProtKB/Swiss-Prot
    Q30201
    Related
    ENSP00000420802.1, ENST00000461397.5
    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
  7. NM_139007.3NP_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
    ENSP00000259699.6, ENST00000349999.8
    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
  8. NM_139008.3NP_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, U91328
    Consensus CDS
    CCDS54975.1
    UniProtKB/Swiss-Prot
    Q30201
    Related
    ENSP00000420559.1, ENST00000488199.5
    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
  9. NM_139009.3NP_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
    Related
    ENSP00000380217.3, ENST00000397022.7
    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
  10. NM_139010.3NP_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
    Related
    ENSP00000312342.5, ENST00000353147.9
    Conserved Domains (1) summary
    cd07698
    Location:27118
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
  11. NM_139011.3NP_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
    Related
    ENSP00000315936.4, ENST00000352392.8

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20211119

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    Range
    26087347..26098343
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

RNA

  1. XR_241893.4 RNA Sequence

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.
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