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 disor... See more...

Aliases for HFE Gene

Aliases for HFE Gene

  • Homeostatic Iron Regulator 2 3 5
  • Hereditary Hemochromatosis Protein 3 4
  • High Fe 2 3
  • HLA-H 3 4
  • Hereditary Hemochromatosis Protein HLA-H 3
  • MHC Class I-Like Protein HFE 3
  • Hemochromatosis 2
  • TFQTL2 3
  • MVCD7 3
  • HFE1 3
  • HLAH 4
  • HH 3

External Ids for HFE Gene

Previous GeneCards Identifiers for HFE Gene

  • GC06P026130
  • GC06P026195
  • GC06P026030

Summaries for HFE Gene

Entrez Gene Summary for HFE Gene

  • 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]

GeneCards Summary for HFE Gene

HFE (Homeostatic Iron Regulator) is a Protein Coding gene. Diseases associated with HFE include Hemochromatosis, Type 1 and Transferrin Serum Level Quantitative Trait Locus 2. Among its related pathways are Hfe effect on hepcidin production. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and peptide antigen binding. An important paralog of this gene is HLA-F.

UniProtKB/Swiss-Prot Summary for HFE Gene

  • Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.

Gene Wiki entry for HFE Gene

Additional gene information for HFE Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HFE Gene

Genomics for HFE Gene

GeneHancer (GH) Regulatory Elements for HFE Gene

Promoters and enhancers for HFE Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HFE on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HFE

Top Transcription factor binding sites by QIAGEN in the HFE gene promoter:
  • C/EBPalpha

Genomic Locations for HFE Gene

Genomic Locations for HFE Gene
chr6:26,087,281-26,098,343
(GRCh38/hg38)
Size:
11,063 bases
Orientation:
Plus strand
chr6:26,087,509-26,098,571
(GRCh37/hg19)
Size:
11,063 bases
Orientation:
Plus strand

Genomic View for HFE Gene

Genes around HFE on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HFE Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HFE Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HFE Gene

Proteins for HFE Gene

  • Protein details for HFE Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q30201-HFE_HUMAN
    Recommended name:
    Hereditary hemochromatosis protein
    Protein Accession:
    Q30201
    Secondary Accessions:
    • B2CKL0
    • O75929
    • O75930
    • O75931
    • Q17RT0
    • Q96KU5
    • Q96KU6
    • Q96KU7
    • Q96KU8
    • Q9HC64
    • Q9HC68
    • Q9HC70
    • Q9HC83

    Protein attributes for HFE Gene

    Size:
    348 amino acids
    Molecular mass:
    40108 Da
    Quaternary structure:
    • Binds TFR through the extracellular domain in a pH-dependent manner.
    Miscellaneous:
    • [Isoform 1]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Three dimensional structures from OCA and Proteopedia for HFE Gene

    Alternative splice isoforms for HFE Gene

neXtProt entry for HFE Gene

Post-translational modifications for HFE Gene

  • Glycosylation at Asn130, Asn234, and Asn110
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for HFE Gene

Domains & Families for HFE Gene

Gene Families for HFE Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for HFE Gene

Suggested Antigen Peptide Sequences for HFE Gene

GenScript: Design optimal peptide antigens:
  • HFE (F5B2M9_HUMAN)
  • HLA-H (HFE_HUMAN)
  • Hemochromatosis (Q86WL1_HUMAN)
  • Hereditary hemochromatosis protein HLA-H (Q8MH46_HUMAN)
  • Hereditary hemochromatosis protein (Q9BXI5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q30201

UniProtKB/Swiss-Prot:

HFE_HUMAN :
  • Belongs to the MHC class I family.
Family:
  • Belongs to the MHC class I family.
genes like me logo Genes that share domains with HFE: view

Function for HFE Gene

Molecular function for HFE Gene

UniProtKB/Swiss-Prot Function:
Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.
GENATLAS Biochemistry:
HFE protein,defective in HH normally expressed in cryptal enterocytes of the duodenum and in placenta,complexing with beta 2 microglobulin and transferrin receptor (TFR2),negative modulator of the uptake of transferrin-bound iron from plasma

Phenotypes From GWAS Catalog for HFE Gene

Gene Ontology (GO) - Molecular Function for HFE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding IPI 10638746
GO:0005515 protein binding IPI 15880641
GO:0030881 beta-2-microglobulin binding IPI 9465039
GO:0039706 co-receptor binding IPI 22728873
GO:0042605 NOT peptide antigen binding IKR 8696333
genes like me logo Genes that share ontologies with HFE: view
genes like me logo Genes that share phenotypes with HFE: view

Human Phenotype Ontology for HFE Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HFE Gene

MGI Knock Outs for HFE:
  • Hfe Hfe<tm1.1Gfn>
  • Hfe Hfe<tm2Nca>
  • Hfe Hfe<tm1Sly>
  • Hfe Hfe<tm1Gfn>
  • Hfe Hfe<tm1.1Wsr>

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids for HFE

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for HFE Gene

Localization for HFE Gene

Subcellular locations from UniProtKB/Swiss-Prot for HFE Gene

Cell membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HFE gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 5
endosome 5
cytoskeleton 3
mitochondrion 3
cytosol 3
endoplasmic reticulum 2
lysosome 2
golgi apparatus 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HFE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IBA,IDA 21173098
GO:0005623 cell IEA --
GO:0005654 nucleoplasm IDA --
GO:0005769 early endosome IDA 15880641
GO:0005886 plasma membrane TAS,IBA --
genes like me logo Genes that share ontologies with HFE: view

Pathways & Interactions for HFE Gene

PathCards logo

SuperPathways for HFE Gene

genes like me logo Genes that share pathways with HFE: view

Pathways by source for HFE Gene

1 BioSystems pathway for HFE Gene

Gene Ontology (GO) - Biological Process for HFE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001916 positive regulation of T cell mediated cytotoxicity IBA 21873635
GO:0002474 NOT antigen processing and presentation of peptide antigen via MHC class I IKR 8696333
GO:0002476 antigen processing and presentation of endogenous peptide antigen via MHC class Ib IBA 21873635
GO:0002486 antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent IBA 21873635
GO:0002626 negative regulation of T cell antigen processing and presentation IEA --
genes like me logo Genes that share ontologies with HFE: view

No data available for SIGNOR curated interactions for HFE Gene

Drugs & Compounds for HFE Gene

(18) Drugs for HFE Gene - From: PharmGKB, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Iron Approved, Experimental Pharma 1496
Adalimumab Approved Pharma 587
heme Pharma Agonist 0

(14) Additional Compounds for HFE Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with HFE: view

Transcripts for HFE Gene

mRNA/cDNA for HFE Gene

12 REFSEQ mRNAs :
35 NCBI additional mRNA sequence :
14 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for HFE

Alternative Splicing Database (ASD) splice patterns (SP) for HFE Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6 ^ 7a · 7b · 7c · 7d
SP1: - -
SP2: - -
SP3: - - -
SP4: - - -
SP5: - - -
SP6: - - - -
SP7: - - - -
SP8: - - - - -
SP9: - - - - -
SP10: -
SP11: - - - - - - -

Relevant External Links for HFE Gene

GeneLoc Exon Structure for
HFE

Expression for HFE Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HFE Gene

Protein differential expression in normal tissues from HIPED for HFE Gene

This gene is overexpressed in Spleen (31.0) and Placenta (12.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HFE Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HFE

SOURCE GeneReport for Unigene cluster for HFE Gene:

Hs.233325

mRNA Expression by UniProt/SwissProt for HFE Gene:

Q30201-HFE_HUMAN
Tissue specificity: Expressed in all tissues tested except brain.

Evidence on tissue expression from TISSUES for HFE Gene

  • Intestine(4.6)
  • Liver(3.3)
  • Blood(2.7)
  • Heart(2.3)
  • Nervous system(2.3)
  • Muscle(2.1)
  • Pancreas(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HFE Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • lymphatic
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • pituitary gland
  • salivary gland
  • skull
Thorax:
  • breast
  • chest wall
  • clavicle
  • esophagus
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • abdominal wall
  • gallbladder
  • intestine
  • kidney
  • liver
  • pancreas
  • small intestine
  • spleen
Pelvis:
  • fallopian tube
  • ovary
  • pelvis
  • penis
  • prostate
  • testicle
  • uterus
  • vagina
  • vulva
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • nail
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • hair
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal column
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with HFE: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Protein tissue co-expression partners for HFE Gene

Orthologs for HFE Gene

This gene was present in the common ancestor of chordates.

Orthologs for HFE Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia HFE 31 30
  • 99.9 (n)
OneToOne
cow
(Bos Taurus)
Mammalia HFE 31 30
  • 83.24 (n)
OneToOne
dog
(Canis familiaris)
Mammalia HFE 31 30
  • 82.13 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hfe 30
  • 78.3 (n)
mouse
(Mus musculus)
Mammalia Hfe 17 31 30
  • 77.23 (n)
oppossum
(Monodelphis domestica)
Mammalia HFE 31
  • 59 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 35 (a)
ManyToMany
chicken
(Gallus gallus)
Aves -- 31
  • 31 (a)
ManyToMany
-- 31
  • 31 (a)
ManyToMany
-- 31
  • 30 (a)
ManyToMany
-- 31
  • 30 (a)
ManyToMany
-- 31
  • 30 (a)
ManyToMany
-- 31
  • 29 (a)
ManyToMany
BFIV21 31
  • 29 (a)
ManyToMany
BF1 31
  • 29 (a)
ManyToMany
-- 31
  • 28 (a)
ManyToMany
-- 31
  • 28 (a)
ManyToMany
-- 31
  • 28 (a)
ManyToMany
-- 31
  • 26 (a)
ManyToMany
-- 31
  • 26 (a)
ManyToMany
-- 31
  • 25 (a)
ManyToMany
-- 31
  • 24 (a)
ManyToMany
-- 31
  • 24 (a)
ManyToMany
-- 31
  • 24 (a)
ManyToMany
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 39 (a)
ManyToMany
-- 31
  • 38 (a)
ManyToMany
-- 31
  • 38 (a)
ManyToMany
-- 31
  • 35 (a)
ManyToMany
-- 31
  • 33 (a)
ManyToMany
-- 31
  • 33 (a)
ManyToMany
-- 31
  • 33 (a)
ManyToMany
-- 31
  • 32 (a)
ManyToMany
-- 31
  • 32 (a)
ManyToMany
-- 31
  • 32 (a)
ManyToMany
-- 31
  • 32 (a)
ManyToMany
-- 31
  • 31 (a)
ManyToMany
-- 31
  • 31 (a)
ManyToMany
-- 31
  • 31 (a)
ManyToMany
-- 31
  • 31 (a)
ManyToMany
-- 31
  • 31 (a)
ManyToMany
-- 31
  • 29 (a)
ManyToMany
-- 31
  • 29 (a)
ManyToMany
-- 31
  • 26 (a)
ManyToMany
-- 31
  • 26 (a)
ManyToMany
Species where no ortholog for HFE was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for HFE Gene

ENSEMBL:
Gene Tree for HFE (if available)
TreeFam:
Gene Tree for HFE (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HFE: view image

Paralogs for HFE Gene

(135) SIMAP similar genes for HFE Gene using alignment to 42 proteins:

  • HFE_HUMAN
  • F5B2M9_HUMAN
  • F8W7W8_HUMAN
  • G3LGQ4_HUMAN
  • G3LGQ5_HUMAN
  • G3LGQ6_HUMAN
  • G3LGQ7_HUMAN
  • G3LGQ9_HUMAN
  • G3LGR0_HUMAN
  • G3LGR1_HUMAN
  • H2E8T4_HUMAN
  • H2E8T5_HUMAN
  • H2E8T7_HUMAN
  • H2E8T8_HUMAN
  • H2EQK2_HUMAN
  • H7C4K4_HUMAN
  • I1VA54_HUMAN
  • I1VA55_HUMAN
  • I1VA56_HUMAN
  • I1VA57_HUMAN
  • I1VA63_HUMAN
  • I1VA65_HUMAN
  • I1VA66_HUMAN
  • I1VA70_HUMAN
  • I1VA71_HUMAN
  • I1VA72_HUMAN
  • J9QF30_HUMAN
  • K0I859_HUMAN
  • K0IIP4_HUMAN
  • Q6B0J5_HUMAN
  • Q86WL1_HUMAN
  • Q8MH46_HUMAN
  • Q9BXI5_HUMAN
  • Q9HC63_HUMAN
  • Q9HC65_HUMAN
  • Q9HC66_HUMAN
  • Q9HC67_HUMAN
  • Q9HC69_HUMAN
  • Q9HC71_HUMAN
  • Q9HC72_HUMAN
  • Q9TQ79_HUMAN
  • Q9UK37_HUMAN
genes like me logo Genes that share paralogs with HFE: view

Variants for HFE Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for HFE Gene

HFE_HUMAN-Q30201
Genetic variations in HFE define the transferrin serum level quantitative trait locus 2 (TFQTL2) [MIM:614193]. Iron is essential for biochemical functions such as oxygen transport and oxidative phosphorylation. Excessive iron can cause iron-overload-related liver diseases, whereas iron deficiency can lead to anemia. Iron status can be assessed by measuring the levels of serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HFE Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
573282 Uncertain Significance: Hereditary hemochromatosis 26,092,690(+) C/A MISSENSE_VARIANT,INTRON_VARIANT
rs111033557 Benign: HFE POLYMORPHISM. - 26,090,939(+) G/Ap.Val59Met MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,INTRON_VARIANT
rs111033558 Pathogenic: Hemochromatosis type 1. Hemochromatosis 1 (HFE1) [MIM:235200] 26,093,215(+) G/Tp.Arg330Met MISSENSE_VARIANT
rs111033563 Pathogenic: Hemochromatosis type 1. Hemochromatosis 1 (HFE1) [MIM:235200] 26,092,916(+) A/Cp.Gln283Pro MISSENSE_VARIANT,INTRON_VARIANT
rs114758821 Benign: Hereditary hemochromatosis 26,087,461(+) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for HFE Gene

Structural Variations from Database of Genomic Variants (DGV) for HFE Gene

Variant ID Type Subtype PubMed ID
dgv5926n100 CNV gain 25217958
nsv1023453 CNV gain 25217958
nsv428137 CNV loss 18775914

Variation tolerance for HFE Gene

Residual Variation Intolerance Score: 83.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.56; 72.23% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HFE Gene

Human Gene Mutatio