HJV Gene

Name hemojuvelin BMP co-receptor
Description 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]
Summary
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HJV is a glycosylphosphatidylinositol‐anchored protein predominantly expressed in the liver and skeletal muscle, where it functions as a co‐receptor for bone morphogenetic proteins (BMPs) to potentiate BMP/Smad signaling and drive hepcidin expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " \n In its membrane‐bound (cell‐associated) form, HJV enhances BMP responsiveness, leading to adequate induction of hepcidin; conversely, the generation of a soluble form—achieved by proteolytic cleavage via furin and the serine protease matriptase‑2 (TMPRSS6)—produces a competitive inhibitor that suppresses BMP signaling and thereby downregulates hepcidin expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mutations in the HJV gene are responsible for juvenile hemochromatosis, a severe early‐onset disorder characterized by low hepcidin levels and pathological iron overload."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " \n Furthermore, HJV function is modulated by its interaction with other proteins such as neogenin, which appears to stabilize the molecule and facilitate its role in BMP signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, HJV serves as a molecular switch in iron sensing by differentially regulating hepcidin expression in response to extracellular iron levels. In its membrane‐bound state, HJV enhances BMP‐mediated hepcidin transcription to limit iron accumulation, while its soluble counterpart counteracts this pathway. These multifaceted roles underscore HJV’s central contribution to maintaining iron balance, as confirmed by multiple independent studies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "George Papanikolaou, Mark E Samuels, Erwin H Ludwig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1274"}], "href": "https://doi.org/10.1038/ng1274"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14647275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14647275"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jaroslav Truksa, Hongfan Peng, Pauline Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0603124103"}], "href": "https://doi.org/10.1073/pnas.0603124103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16801541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16801541"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Laura Silvestri, Alessia Pagani, Antonella Nai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2008.09.012"}], "href": "https://doi.org/10.1016/j.cmet.2008.09.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18976966"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18976966"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Laura Silvestri, Alessia Pagani, Clara Camaschella "}, {"type": "b", "children": [{"type": "t", "text": "Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-07-100677"}], "href": "https://doi.org/10.1182/blood-2007-07-100677"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17938254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17938254"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lan Lin, Y Paul Goldberg, Tomas Ganz "}, {"type": "b", "children": [{"type": "t", "text": "Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2005-05-1845"}], "href": "https://doi.org/10.1182/blood-2005-05-1845"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15998830"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15998830"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lan Lin, Elizabeta Nemeth, Julia B Goodnough, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Cells Mol Dis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bcmd.2007.06.023"}], "href": "https://doi.org/10.1016/j.bcmd.2007.06.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17869549"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17869549"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Antonella Nai, Alessia Pagani, Laura Silvestri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin levels in normal individuals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-06-364034"}], "href": "https://doi.org/10.1182/blood-2011-06-364034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21873547"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21873547"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Elizabeta Nemeth, Antonella Roetto, Giovanni Garozzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepcidin is decreased in TFR2 hemochromatosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-08-3042"}], "href": "https://doi.org/10.1182/blood-2004-08-3042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15486069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15486069"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Carmela Lanzara, Antonella Roetto, Filomena Daraio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-01-0192"}], "href": "https://doi.org/10.1182/blood-2004-01-0192"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14982873"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14982873"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "An-Sheng Zhang, Anthony P West, Anne E Wyman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M506207200"}], "href": "https://doi.org/10.1074/jbc.M506207200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16103117"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16103117"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Dae-Hoon Lee, Li-Juan Zhou, Zheng Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-11-251199"}], "href": "https://doi.org/10.1182/blood-2009-11-251199"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20065295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20065295"}]}]}]}
NCBI Gene ID 148738
API
Download Associations
Predicted Functions View HJV's ARCHS4 Predicted Functions.
Co-expressed Genes View HJV's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View HJV's ARCHS4 Predicted Functions.

Functional Associations

HJV has 1,499 functional associations with biological entities spanning 5 categories (disease, phenotype or trait, functional term, phrase or reference, chemical, cell line, cell type or tissue, gene, protein or microRNA) extracted from 25 datasets.

Click the + buttons to view associations for HJV from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of HJV gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
ClinVar Gene-Phenotype Associations 2025 phenotypes associated with HJV gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of HJV gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing HJV protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with HJV protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
DISEASES Curated Gene-Disease Association Evidence Scores 2025 diseases involving HJV gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with HJV gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
GO Biological Process Annotations 2025 biological processes involving HJV gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2025 cellular components containing HJV protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by HJV gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of HJV gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
IMPC Knockout Mouse Phenotypes phenotypes of mice caused by HJV gene knockout from the IMPC Knockout Mouse Phenotypes dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of HJV gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of HJV gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
KEGG Pathways 2026 pathways involving HJV protein from the KEGG Pathways 2026 dataset.
MoTrPAC Rat Endurance Exercise Training tissue samples with high or low expression of HJV gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset.
PFOCR Pathway Figure Associations 2024 pathways involving HJV protein from the Wikipathways PFOCR 2024 dataset.
Reactome Pathways 2024 pathways involving HJV protein from the Reactome Pathways 2024 dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of HJV gene from the Rummagene Transcription Factor Associations 2026 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of HJV gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of HJV gene from the RummaGEO Gene Perturbation Signatures dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of HJV protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of HJV protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with HJV protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2024 pathways involving HJV protein from the WikiPathways Pathways 2024 dataset.