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 ... See more...

Aliases for HJV Gene

Aliases for HJV Gene

  • Hemojuvelin BMP Co-Receptor 2 3 5
  • Hemojuvelin 2 3 4
  • RGMC 2 3 4
  • Hemochromatosis Type 2 (Juvenile) 2 3
  • Hemochromatosis Type 2 Protein 3 4
  • Repulsive Guidance Molecule C 2 3
  • RGM Domain Family Member C 3 4
  • Hemojuvelin BMP Coreceptor 3 4
  • Haemojuvelin 2 3
  • HFE2A 2 3
  • HFE2 3 4
  • JH 2 3
  • HJV 5

External Ids for HJV Gene

Previous HGNC Symbols for HJV Gene

  • HFE2

Summaries for HJV Gene

Entrez Gene Summary for HJV 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 HJV Gene

HJV (Hemojuvelin BMP Co-Receptor) is a Protein Coding gene. Diseases associated with HJV include Hemochromatosis, Type 2A and Hemochromatosis Type 2. Among its related pathways are Netrin-1 signaling and Signaling by BMP. An important paralog of this gene is RGMA.

UniProtKB/Swiss-Prot Summary for HJV 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 HJV Gene

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

Genomics for HJV Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HJV 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 HJV on the GeneHancer Hub at the UCSC Golden Path

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

Genomic Locations for HJV Gene

Genomic Locations for HJV Gene
chr1:146,017,468-146,036,746
(GRCh38/hg38)
Size:
19,279 bases
Orientation:
Minus strand
chr1:145,413,095-145,417,545
(GRCh37/hg19)
Size:
4,451 bases
Orientation:
Plus strand

Genomic View for HJV Gene

Genes around HJV on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for HJV Gene

Proteins for HJV Gene

  • Protein details for HJV 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 HJV 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 HJV Gene

    Alternative splice isoforms for HJV Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HJV Gene

Post-translational modifications for HJV 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 HJV activity in BMP signaling and thefore iron homeostasis.
  • Glycosylation at Asn118, Asn213, and Asn372
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for HJV Gene

Domains & Families for HJV Gene

Gene Families for HJV Gene

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

Protein Domains for HJV Gene

InterPro:
Blocks:
  • Repulsive guidance molecule, C-terminal
ProtoNet:

Suggested Antigen Peptide Sequences for HJV Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ79501, highly similar to Hemojuvelin (A8K466_HUMAN)
  • RGM domain family member C (RGMC_HUMAN)

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 HJV: view

Function for HJV Gene

Molecular function for HJV 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 HJV Gene

Gene Ontology (GO) - Molecular Function for HJV Gene

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

Human Phenotype Ontology for HJV Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HJV Gene

MGI Knock Outs for HJV:
  • Hjv Hjv<tm1Arbr>
  • Hjv Hjv<tm1Nca>
  • Hjv Hjv<tm1b(KOMP)Wtsi>

Animal Model Products

  • Taconic Biosciences Mouse Models for HJV

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HJV

Clone Products

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

Localization for HJV Gene

Subcellular locations from UniProtKB/Swiss-Prot for HJV 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 HJV gene
Compartment Confidence
plasma membrane 5
extracellular 5
mitochondrion 2
nucleus 2
endosome 2
cytosol 2
lysosome 2
cytoskeleton 1
endoplasmic reticulum 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for HJV Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IDA 17938254
GO:0005623 cell IEA --
GO:0005886 plasma membrane IDA 16075058
GO:0009986 cell surface IEA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with HJV: view

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

Pathways & Interactions for HJV Gene

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

Pathways by source for HJV Gene

2 BioSystems pathways for HJV Gene
3 Reactome pathways for HJV Gene
1 KEGG pathway for HJV Gene

Gene Ontology (GO) - Biological Process for HJV 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 HJV: view

No data available for SIGNOR curated interactions for HJV Gene

Drugs & Compounds for HJV Gene

(1) Drugs for HJV Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Iron Approved, Experimental Pharma 1560
genes like me logo Genes that share compounds with HJV: view

Transcripts for HJV Gene

mRNA/cDNA for HJV Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HJV

Clone Products

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

No ASD Table

Relevant External Links for HJV Gene

GeneLoc Exon Structure for
HJV

Expression for HJV Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

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

mRNA Expression by UniProt/SwissProt for HJV Gene:

Q6ZVN8-RGMC_HUMAN
Tissue specificity: Adult and fetal liver, heart, and skeletal muscle.

Evidence on tissue expression from TISSUES for HJV Gene

  • Liver(4.7)
  • Muscle(4.7)
  • Nervous system(4.4)
  • Heart(3)
  • Intestine(2.6)
  • Blood(2.2)
  • Kidney(2.1)
  • Pancreas(2.1)

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

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • skeletal muscle
  • skeleton
  • urinary
Regions:
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 HJV: view

No data available for mRNA expression in normal human tissues , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for HJV Gene

Orthologs for HJV Gene

This gene was present in the common ancestor of animals.

Orthologs for HJV Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia HFE2 30 31
  • 99.67 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia HFE2 30 31
  • 91.25 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia HFE2 30 31
  • 90.5 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Hfe2 30
  • 84.44 (n)
Mouse
(Mus musculus)
Mammalia Hfe2 30 31
  • 84.09 (n)
OneToOne
Hjv 17
Oppossum
(Monodelphis domestica)
Mammalia HFE2 31
  • 81 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia HFE2 31
  • 62 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 57 (a)
OneToMany
-- 31
  • 55 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia hfe2 30
  • 62.1 (n)
Zebrafish
(Danio rerio)
Actinopterygii hfe2 30 31
  • 55.49 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea drag-1 31
  • 22 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 39 (a)
OneToMany
Species where no ortholog for HJV was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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 HJV Gene

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

Paralogs for HJV Gene

Paralogs for HJV Gene

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

Variants for HJV Gene

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

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
639262 Uncertain Significance: Hemochromatosis type 2A 146,018,655(-) CCTT/C INFRAME_DELETION
646197 Pathogenic: not provided 146,019,611(-) AC/A FRAMESHIFT_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON_VARIANT
658524 Uncertain Significance: Hemochromatosis type 2A; not provided 146,018,454(-) C/T MISSENSE_VARIANT
662092 Uncertain Significance: Hemochromatosis type 2A 146,019,390(-) A/T MISSENSE_VARIANT,INTRON_VARIANT
664777 Uncertain Significance: Hemochromatosis type 2A; not provided 146,018,354(-) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for HJV Gene

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

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

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

Disorders for HJV Gene

MalaCards: The human disease database

(35) MalaCards diseases for HJV Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hemochromatosis, type 2a
  • hfe2a
hemochromatosis type 2
  • hfe2
hemochromatosis, type 1
  • hfe1
iron metabolism disease
  • disorder of iron metabolism
hemosiderosis
  • haemosiderosis
- elite association - COSMIC cancer census association via MalaCards
Search HJV 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.
genes like me logo Genes that share disorders with HJV: view

No data available for Genatlas for HJV Gene

Publications for HJV 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 23
  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 23
  3. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. (PMID: 16604073) Babitt JL … Lin HY (Nature genetics 2006) 3 4 23
  4. Genetic abnormalities and juvenile hemochromatosis: mutations of the HJV gene encoding hemojuvelin. (PMID: 14982867) Lee PL … Barton JC (Blood 2004) 3 4 23
  5. Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis. (PMID: 14982873) Lanzara C … Camaschella C (Blood 2004) 3 4 23

Products for HJV Gene

  • Signalway ELISA kits for HJV
  • Signalway Proteins for HJV

Sources for HJV Gene