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HFE2 Gene(Protein Coding)

Hemochromatosis Type 2 (Juvenile)

GCID:
GC01M146017
GIFtS:
62
Genes Participants
UDN Logo

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. 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

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

Genomics for HFE2 Gene

Products:

  1. Regulatory Element

Regulatory Elements for HFE2 Gene

Enhancers for HFE2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH01G145976 2.1 FANTOM5 Ensembl ENCODE dbSUPER 11.8 +54.5 54464 10.6 YBX1 FEZF1 YY1 ZNF143 ZNF263 SP3 NFYC TBX21 MEF2D SSRP1 ANKRD35 HFE2 RBM8A LIX1L-AS1 PEX11B ENSG00000213240 GNRHR2 NOTCH2NL POLR3C LIX1L
GH01G145990 1.8 FANTOM5 ENCODE dbSUPER 11.9 +41.4 41404 10.5 MLX CREB3L1 AGO1 FEZF1 DMAP1 YY1 SLC30A9 ZNF263 NFYC MEF2D LIX1L-AS1 ENSG00000213240 TXNIP HFE2 RBM8A PEX11B GNRHR2 CD160 POLR3C ANKRD34A
GH01G145954 1.3 Ensembl ENCODE 10.7 +80.0 80048 4.2 HDGF PKNOX1 FOXA2 ARNT WRNIP1 ARID4B SIN3A YBX1 DMAP1 YY1 RBM8A LIX1L-AS1 GNRHR2 PEX11B TXNIP ITGA10 HFE2 ENSG00000213240 ANKRD35 POLR3C
GH01G145917 1.1 ENCODE 10.4 +117.9 117925 2.8 HDGF ARNT ZFP64 ARID4B SIN3A YY1 ZNF143 ZNF263 SP3 ZHX2 ANKRD35 HFE2 ENSG00000213240 POLR3C LIX1L-AS1 PEX11B ITGA10
GH01G145987 0.9 ENCODE dbSUPER 11.8 +48.7 48717 0.8 ESRRA ZNF3 RARA ZNF121 ZNF316 POLR2A EGR1 EMSY RBFOX2 SUPT5H ENSG00000213240 HFE2 RBM8A LIX1L-AS1 PEX11B GNRHR2 PIR45915 GC01P145988
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around HFE2 on UCSC Golden Path with GeneCards custom track

Promoters for HFE2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000012962 -654 4801 MLX CREB3L1 FEZF1 DMAP1 YY1 SLC30A9 ZNF143 ZNF548 SP3 TBX21

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

Genomic Location for HFE2 Gene

Chromosome:
1
Start:
146,017,468 bp from pter
End:
146,036,746 bp from pter
Size:
19,279 bases
Orientation:
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 Structure • Gene Density

RefSeq DNA sequence for HFE2 Gene

Proteins for HFE2 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

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

    Protein Symbol:
    Q6ZVN8-RGMC_HUMAN
    Recommended name:
    Hemojuvelin
    Protein Accession:
    Q6ZVN8
    Secondary Accessions:
    • B1ALI7
    • Q2PQ63
    • Q6IMF6
    • Q8NAH2
    • Q8WVJ5

    Protein attributes for HFE2 Gene

    Size:
    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

    UniProtKB/Swiss-Prot:

neXtProt entry for HFE2 Gene

Protein Expression for HFE2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

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 posLast=118118, isoforms=2213, and isoforms=2, 3372
  • Modification sites at PhosphoSitePlus

Other Protein References for HFE2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for HFE2 (RGM-C/Hemojuvelin)

No data available for DME Specific Peptides for HFE2 Gene

Domains & Families for HFE2 Gene

Protein Domains for HFE2 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for HFE2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q6ZVN8

UniProtKB/Swiss-Prot:

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

No data available for Gene Families for HFE2 Gene

Function for HFE2 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

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.

Gene Ontology (GO) - Molecular Function for HFE2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001948 glycoprotein binding IPI 22728873
GO:0005102 receptor binding IPI 18326817
GO:0005515 protein binding IPI 18335997
GO:0015026 coreceptor activity IEA,IDA 16604073
GO:0036122 BMP binding IPI,IEA 18335997
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

CRISPR Products

Inhibitory RNA Products

Flow Cytometry 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

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 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

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 from RNA polymerase II promoter ISS --
GO:0006879 cellular iron ion homeostasis ISS --
GO:0016540 protein autoprocessing IMP 18335997
GO:0030509 BMP signaling pathway IMP,IEA 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

Products:

  1. Drug

(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
Fe2+
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
 15438-31-0
genes like me logo Genes that share compounds with HFE2: view

Transcripts for HFE2 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for HFE2 Gene

(6) REFSEQ mRNAs :
(11) Additional mRNA sequences :
(64) Selected AceView cDNA sequences:
(7) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for HFE2 Gene

Hemochromatosis type 2 (juvenile):
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Flow Cytometry Products

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

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b · 3c ^ 4 ^ 5a · 5b
SP1:
SP2: -
SP3: - -
SP4: - - - - - -
SP5:

Relevant External Links for HFE2 Gene

GeneLoc Exon Structure for
HFE2
ECgene alternative splicing isoforms for
HFE2

Expression for HFE2 Gene

Products:

  1. Primer

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

mRNA expression in normal human tissues for HFE2 Gene
mRNA expression by BioGPS for HFE2 GenemRNA expression by GTEx 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:

HFE2

SOURCE GeneReport for Unigene cluster for HFE2 Gene:

Hs.632436

mRNA Expression by UniProt/SwissProt for HFE2 Gene:

Q6ZVN8-RGMC_HUMAN
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
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • skeletal muscle
  • skeleton
  • urinary
Organs:
Head and neck:
  • brain
  • ear
  • eye
  • head
  • mouth
  • pituitary gland
  • salivary gland
Thorax:
  • breast
  • esophagus
  • heart
  • heart valve
Abdomen:
  • kidney
  • liver
  • pancreas
  • spleen
Pelvis:
  • ovary
  • penis
  • prostate
  • testicle
  • uterus
  • vagina
  • vulva
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • nail
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • 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

Primer Products

Orthologs for HFE2 Gene

This gene was present in the common ancestor of animals.

Orthologs for HFE2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia HFE2 34 35
  • 99.67 (n)
cow
(Bos Taurus)
 Mammalia HFE2 34 35
  • 91.25 (n)
dog
(Canis familiaris)
 Mammalia HFE2 34 35
  • 90.5 (n)
rat
(Rattus norvegicus)
 Mammalia Hfe2 34
  • 84.44 (n)
mouse
(Mus musculus)
 Mammalia Hfe2 34 16 35
  • 84.09 (n)
oppossum
(Monodelphis domestica)
 Mammalia HFE2 35
  • 81 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia HFE2 35
  • 62 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia -- 35
  • 57 (a)
 OneToMany
-- 35
  • 55 (a)
 OneToMany
tropical clawed frog
(Silurana tropicalis)
 Amphibia hfe2 34
  • 62.1 (n)
zebrafish
(Danio rerio)
 Actinopterygii hfe2 34 35
  • 55.49 (n)
worm
(Caenorhabditis elegans)
 Secernentea drag-1 35
  • 22 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 35
  • 39 (a)
 OneToMany
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

ENSEMBL:
Gene Tree for HFE2 (if available)
TreeFam:
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 Sequence Context AA Info Type
rs121434374 Pathogenic, Hemochromatosis 2A (HFE2A) [MIM:602390] 146,018,395(-) GGGTG(A/C/G)CCTCC reference, missense, stop-gained
rs28940586 Pathogenic, Hemochromatosis 2A (HFE2A) [MIM:602390] 146,019,594(-) GCCTC(C/G/T)GTCGA intron-variant, reference, missense, utr-variant-5-prime
rs74315323 Pathogenic, Hemochromatosis 2A (HFE2A) [MIM:602390] 146,018,399(-) TGGGG(G/T)GTGCC reference, missense
rs74315325 Pathogenic, Hemochromatosis 2A (HFE2A) [MIM:602390] 146,018,693(-) CACCA(A/T)CATAT reference, missense, utr-variant-5-prime
rs74315327 Pathogenic, Hemochromatosis 2A (HFE2A) [MIM:602390] 146,019,530(-) GGACC(C/T)CGCCT intron-variant, reference, missense, utr-variant-5-prime

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)

Relevant External Links for HFE2 Gene

Human Gene Mutation Database (HGMD)
HFE2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HFE2

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

Disorders for HFE2 Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
hemochromatosis, type 2a
  • hemochromatosis type 2a
hemochromatosis type 2
  • hfe2
hemochromatosis
  • hfe hemochromatosis, modifier of
juvenile hereditary hemochromatosis
  • hemochromatosis
hjv -related juvenile hemochromatosis
  • hemochromatosis, type 2a
- elite association - COSMIC cancer census association via MalaCards
Search HFE2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

RGMC_HUMAN
  • 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.

Relevant External Links for HFE2

Genetic Association Database (GAD)
HFE2
Human Genome Epidemiology (HuGE) Navigator
HFE2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HFE2
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 Y.P. (Nat. Genet. 2004) 2 3 4 22 64
  2. 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 64
  3. Non-classical hereditary hemochromatosis in Portugal: novel mutations identified in iron metabolism-related genes. (PMID: 18762941) Mendes A.I. … Faustino P. (Ann. Hematol. 2009) 3 22 46 64
  4. 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) AltA"s A. … Baiget M. (Ann. Hematol. 2009) 3 22 46 64
  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. (Am. J. Hum. Genet. 2007) 3 22 46 64

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