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Aliases for HFE2 Gene

Aliases for HFE2 Gene

  • Hemochromatosis Type 2 (Juvenile) 2 3 5
  • Hemochromatosis Type 2 Protein 3 4
  • Repulsive Guidance Molecule C 2 3
  • RGM Domain Family Member C 3 4
  • RGMC 3 4
  • HJV 3 4
  • Haemojuvelin 3
  • Hemojuvelin 3
  • HFE2A 3
  • JH 3

External Ids for HFE2 Gene

Previous GeneCards Identifiers for HFE2 Gene

  • GC01U990224
  • GC01P143161
  • GC01P142902
  • GC01P144124
  • GC01P145413
  • GC01P119377

Summaries for HFE2 Gene

Entrez Gene Summary for HFE2 Gene

  • The product of this gene is involved in iron metabolism. It may be a component of the signaling pathway which activates hepcidin or it may act as a modulator of hepcidin expression. It could also represent the cellular receptor for hepcidin. Two uORFs in the 5' UTR negatively regulate the expression and activity of the encoded protein. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Defects in this gene are the cause of hemochromatosis type 2A, also called juvenile hemochromatosis (JH). JH is an early-onset autosomal recessive disorder due to severe iron overload resulting in hypogonadotrophic hypogonadism, hepatic fibrosis or cirrhosis and cardiomyopathy, occurring typically before age of 30. [provided by RefSeq, Oct 2015]

GeneCards Summary for HFE2 Gene

HFE2 (Hemochromatosis Type 2 (Juvenile)) is a Protein Coding gene. Diseases associated with HFE2 include Hemochromatosis, Type 2A and Hemochromatosis Type 2. Among its related pathways are Developmental Biology and Hfe effect on hepcidin production. Gene Ontology (GO) annotations related to this gene include coreceptor activity. An important paralog of this gene is RGMA.

UniProtKB/Swiss-Prot for HFE2 Gene

  • Acts as a bone morphogenetic protein (BMP) coreceptor. Through enhancement of BMP signaling regulates hepcidin (HAMP) expression and regulates iron homeostasis.

Gene Wiki entry for HFE2 Gene

Additional gene information for HFE2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HFE2 Gene

Genomics for HFE2 Gene

GeneHancer (GH) Regulatory Elements for HFE2 Gene

Promoters and enhancers for HFE2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01I146034 Promoter/Enhancer 1.9 Ensembl ENCODE dbSUPER 554.6 -0.8 -805 5.6 CLOCK MLX DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ZNF143 ZNF548 HFE2 GC01P146046 PIR58458 TRE-CTC1-1 TRG-TCC2-1 TRH-GTG1-1 TRK-CTT2-1 PIAS3 POLR3C NBPF20
GH01I146019 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE dbSUPER 550.4 +15.4 15442 3.2 HDGF FOXA2 PKNOX1 ARNT ARID4B YY1 GTF3C2 FOS ATF7 RXRA HFE2 ANKRD35 TRE-CTC1-1 TXNIP
GH01I145990 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 11.9 +41.4 41404 10.5 CLOCK MLX FEZF1 DMAP1 IRF4 YY1 SLC30A9 E2F8 NFYC MEF2D TXNIP PIR35110 POLR3C NBPF20 LIX1L-AS1 PIAS3 ENSG00000213240 HFE2 RBM8A GPR89A
GH01I145954 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE 10.7 +80.0 80047 4.2 HDGF PKNOX1 CLOCK SMAD1 ARNT ARID4B SIN3A YBX1 DMAP1 YY1 LIX1L LIX1L-AS1 POLR3C RBM8A GNRHR2 PEX11B TXNIP ITGA10 HFE2 ENSG00000213240
GH01I145976 Enhancer 1.8 FANTOM5 Ensembl ENCODE dbSUPER 11.8 +54.5 54463 10.6 CLOCK YBX1 FEZF1 IRF4 YY1 ZNF213 E2F8 ZNF143 SP3 NFYC NBPF20 POLR3C GPR89A PIAS3 ANKRD35 HFE2 RBM8A LIX1L-AS1 PEX11B ENSG00000213240
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around HFE2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the HFE2 gene promoter:

Genomic Locations for HFE2 Gene

Genomic Locations for HFE2 Gene
19,279 bases
Minus strand

Genomic View for HFE2 Gene

Genes around HFE2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HFE2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HFE2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HFE2 Gene

Proteins for HFE2 Gene

  • Protein details for HFE2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Protein Accession:
    Secondary Accessions:
    • B1ALI7
    • Q2PQ63
    • Q6IMF6
    • Q8NAH2
    • Q8WVJ5

    Protein attributes for HFE2 Gene

    426 amino acids
    Molecular mass:
    45080 Da
    Quaternary structure:
    • Interacts with BMP2 and BMP4 (By similarity). Interacts with BMPR1B. Interacts with TMPRSS6.

    Three dimensional structures from OCA and Proteopedia for HFE2 Gene

    Alternative splice isoforms for HFE2 Gene


neXtProt entry for HFE2 Gene

Post-translational modifications for HFE2 Gene

  • Autocatalytically cleaved at low pH; the two chains remain linked via two disulfide bonds. Also proteolytically processed by TMPRSS6, several fragments being released in the extracellular space; regulates HFE2 activity in BMP signaling and thefore iron homeostasis.
  • Glycosylation at isoforms=2118, isoforms=2213, and posLast=372372
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for HFE2 Gene

Domains & Families for HFE2 Gene

Gene Families for HFE2 Gene

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

Protein Domains for HFE2 Gene

Suggested Antigen Peptide Sequences for HFE2 Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the repulsive guidance molecule (RGM) family.
  • Belongs to the repulsive guidance molecule (RGM) family.
genes like me logo Genes that share domains with HFE2: view

Function for HFE2 Gene

Molecular function for HFE2 Gene

UniProtKB/Swiss-Prot Function:
Acts as a bone morphogenetic protein (BMP) coreceptor. Through enhancement of BMP signaling regulates hepcidin (HAMP) expression and regulates iron homeostasis.

Phenotypes From GWAS Catalog for HFE2 Gene

Gene Ontology (GO) - Molecular Function for HFE2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 receptor binding IPI 18326817
GO:0005515 protein binding IPI 18335997
GO:0015026 coreceptor activity IDA,IEA 16604073
GO:0036122 BMP binding IPI,IEA 18335997
GO:0098821 contributes_to BMP receptor activity IDA 16604073
genes like me logo Genes that share ontologies with HFE2: view
genes like me logo Genes that share phenotypes with HFE2: view

Human Phenotype Ontology for HFE2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HFE2 Gene

MGI Knock Outs for HFE2:

Animal Model Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for HFE2 Gene

Localization for HFE2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HFE2 Gene

Cell membrane; Lipid-anchor, GPI-anchor. Note=Also released in the extracellular space. {ECO:0000269 PubMed:25156943}.

Subcellular locations from

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 HFE2 gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytosol 1

Gene Ontology (GO) - Cellular Components for HFE2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IDA 17938254
GO:0005886 plasma membrane IDA 16075058
GO:0009986 cell surface IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with HFE2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HFE2 Gene

Pathways & Interactions for HFE2 Gene

genes like me logo Genes that share pathways with HFE2: view

Pathways by source for HFE2 Gene

2 BioSystems pathways for HFE2 Gene
3 Reactome pathways for HFE2 Gene

Gene Ontology (GO) - Biological Process for HFE2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II ISS --
GO:0006879 cellular iron ion homeostasis ISS --
GO:0016540 protein autoprocessing IMP 18335997
GO:0030509 BMP signaling pathway IEA,IMP 16604073
GO:0030514 negative regulation of BMP signaling pathway IEA --
genes like me logo Genes that share ontologies with HFE2: view

No data available for SIGNOR curated interactions for HFE2 Gene

Drugs & Compounds for HFE2 Gene

(1) Drugs for HFE2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for HFE2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
genes like me logo Genes that share compounds with HFE2: view

Transcripts for HFE2 Gene

Unigene Clusters for HFE2 Gene

Hemochromatosis type 2 (juvenile):
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for HFE2 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b · 3c ^ 4 ^ 5a · 5b
SP2: -
SP3: - -
SP4: - - - - - -

Relevant External Links for HFE2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HFE2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for HFE2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HFE2 Gene

This gene is overexpressed in Muscle - Skeletal (x33.9), Liver (x10.6), and Heart - Atrial Appendage (x4.2).

Protein differential expression in normal tissues from HIPED for HFE2 Gene

This gene is overexpressed in Colon muscle (61.0) and Breast (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for HFE2 Gene

Protein tissue co-expression partners for HFE2 Gene

NURSA nuclear receptor signaling pathways regulating expression of HFE2 Gene:


SOURCE GeneReport for Unigene cluster for HFE2 Gene:


mRNA Expression by UniProt/SwissProt for HFE2 Gene:

Tissue specificity: Adult and fetal liver, heart, and skeletal muscle.

Evidence on tissue expression from TISSUES for HFE2 Gene

  • Liver(4.7)
  • Muscle(4.6)
  • Nervous system(4)
  • Heart(2.4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HFE2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • skeletal muscle
  • skeleton
  • urinary
Head and neck:
  • brain
  • ear
  • eye
  • head
  • mouth
  • pituitary gland
  • salivary gland
  • breast
  • esophagus
  • heart
  • heart valve
  • kidney
  • liver
  • pancreas
  • spleen
  • ovary
  • penis
  • prostate
  • testicle
  • uterus
  • vagina
  • vulva
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • nail
  • shoulder
  • toe
  • upper limb
  • wrist
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • hair
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with HFE2: view

Orthologs for HFE2 Gene

This gene was present in the common ancestor of animals.

Orthologs for HFE2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia HFE2 33 34
  • 99.67 (n)
(Bos Taurus)
Mammalia HFE2 33 34
  • 91.25 (n)
(Canis familiaris)
Mammalia HFE2 33 34
  • 90.5 (n)
(Rattus norvegicus)
Mammalia Hfe2 33
  • 84.44 (n)
(Mus musculus)
Mammalia Hfe2 33 16 34
  • 84.09 (n)
(Monodelphis domestica)
Mammalia HFE2 34
  • 81 (a)
(Ornithorhynchus anatinus)
Mammalia HFE2 34
  • 62 (a)
(Anolis carolinensis)
Reptilia -- 34
  • 57 (a)
-- 34
  • 55 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia hfe2 33
  • 62.1 (n)
(Danio rerio)
Actinopterygii hfe2 33 34
  • 55.49 (n)
(Caenorhabditis elegans)
Secernentea drag-1 34
  • 22 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 39 (a)
Species where no ortholog for HFE2 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)
  • chicken (Gallus gallus)
  • 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 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)
  • wheat (Triticum aestivum)

Evolution for HFE2 Gene

Gene Tree for HFE2 (if available)
Gene Tree for HFE2 (if available)

Paralogs for HFE2 Gene

Paralogs for HFE2 Gene

(2) SIMAP similar genes for HFE2 Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with HFE2: view

Variants for HFE2 Gene

Sequence variations from dbSNP and Humsavar for HFE2 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs111753853 uncertain-significance, Juvenile hemochromatosis 146,021,632(-) A/G 5_prime_UTR_variant
rs12025510 benign, Hemochromatosis type 2A 146,020,223(-) C/G 5_prime_UTR_variant, coding_sequence_variant, intron_variant, missense_variant
rs121434374 pathogenic, Hemochromatosis type 2A, Hemochromatosis type 1, Hemochromatosis 2A (HFE2A) [MIM:602390] 146,018,395(-) G/C/T coding_sequence_variant, missense_variant, stop_gained
rs121434375 pathogenic, Hemochromatosis type 2A 146,019,672(-) T/A 5_prime_UTR_variant, coding_sequence_variant, intron_variant, stop_gained
rs140919572 uncertain-significance, Juvenile hemochromatosis 146,018,530(-) G/T coding_sequence_variant, synonymous_variant

Structural Variations from Database of Genomic Variants (DGV) for HFE2 Gene

Variant ID Type Subtype PubMed ID
nsv1005055 CNV loss 25217958
nsv2699 CNV insertion 18451855
nsv509457 CNV insertion 20534489
nsv831359 CNV loss 17160897

Variation tolerance for HFE2 Gene

Residual Variation Intolerance Score: 33.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.70; 57.33% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HFE2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HFE2 Gene

Disorders for HFE2 Gene

MalaCards: The human disease database

(12) MalaCards diseases for HFE2 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search HFE2 in MalaCards View complete list of genes associated with diseases


  • Hemochromatosis 2A (HFE2A) [MIM:602390]: A juvenile form of hemochromatosis, a disorder of iron metabolism with excess deposition of iron in a variety of organs leading to their failure, bronze skin pigmentation, hepatic cirrhosis, arthropathy and diabetes. The most common symptoms of juvenile hemochromatosis at presentation are hypogonadism and cardiomyopathy. {ECO:0000269 PubMed:14647275, ECO:0000269 PubMed:14982867, ECO:0000269 PubMed:14982873, ECO:0000269 PubMed:15461631}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for HFE2

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with HFE2: view

No data available for Genatlas for HFE2 Gene

Publications for HFE2 Gene

  1. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. (PMID: 14647275) Papanikolaou G … Goldberg YP (Nature genetics 2004) 2 3 4 22 58
  2. Non-classical hereditary hemochromatosis in Portugal: novel mutations identified in iron metabolism-related genes. (PMID: 18762941) Mendes AI … Faustino P (Annals of hematology 2009) 3 22 44 58
  3. Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene. (PMID: 19214511) Altès A … Baiget M (Annals of hematology 2009) 3 22 44 58
  4. Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia. (PMID: 19357398) Silvestri L … Grandchamp B (Blood 2009) 3 4 22 58
  5. Common variants in the BMP2, BMP4, and HJV genes of the hepcidin regulation pathway modulate HFE hemochromatosis penetrance. (PMID: 17847004) Milet J … Mosser J (American journal of human genetics 2007) 3 22 44 58

Products for HFE2 Gene

Sources for HFE2 Gene

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