Details for: HJV

Gene ID: 148738

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: HJV

Ensembl ID: ENSG00000168509

Description: hemojuvelin BMP co-receptor

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • hepatocyte CL0000182
    CSI 3.76
    rCSI 6.72%
    PRS 99.82
  • centrilobular region hepatocyte CL0019029
    CSI 3.39
    rCSI 8.84%
    PRS 99.97
  • muscle cell CL0000187
    CSI 3.3
    rCSI 6.78%
    PRS 99.63

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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  • Node Size: Proportional to Target Cell CSI magnitude
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  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [HJV](/details-gene/148738), or hemojuvelin BMP co-receptor, is a protein-coding gene located on chromosome 1q21.1. It functions as a crucial co-receptor in the Bone Morphogenetic Protein (BMP) signaling pathway, playing a central role in systemic iron homeostasis. Its primary function is to regulate the expression of hepcidin, the master regulator of iron absorption and distribution. Consistent with this role, [HJV](/details-gene/148738) shows its most significant expression in [hepatocytes](/details-cell/CL0000182) and [muscle cells](/details-cell/CL0000187). Loss-of-function mutations in [HJV](/details-gene/148738) are the cause of type 2 juvenile hemochromatosis ([602390](https://omim.org/entry/602390)), a severe iron overload disorder [[Link](https://doi.org/10.1038/ng1274)]. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [HJV](/details-gene/148738) strongly underscores its role in iron metabolism and cellular signaling. The gene's highest significance index is observed in [hepatocytes](/details-cell/CL0000182) (CSI: 3.76), particularly within the [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 3.39), which are the primary site of hepcidin production. This localization is critical for its function, as HJV on the surface of [hepatocytes](/details-cell/CL0000182) sensitizes the cell to circulating BMP ligands, thereby inducing hepcidin transcription and controlling systemic iron levels [[Link](https://doi.org/10.1038/ng1777)]. Beyond the liver, [HJV](/details-gene/148738) also shows high significance in [muscle cells](/details-cell/CL0000187) (CSI: 3.30). While its role in the liver is well-established for systemic iron regulation, its function in skeletal muscle is less understood but may relate to local iron handling or the regulation of muscle-specific BMP signaling pathways. ## Pathways and Molecular Function The functional annotations for [HJV](/details-gene/148738) are highly consistent with its biological role as a signaling co-receptor. Gene Ontology terms highlight its involvement in the [Bmp signaling pathway](/details-term/GO:0030509) and the [Activin receptor signaling pathway](/details-term/GO:0032924). As a molecular function, it exhibits [Bmp binding](/details-term/GO:0036122) and [coreceptor activity](/details-term/GO:0015026), localizing to the [cell surface](/details-term/GO:0009986) as part of the [Bmp receptor complex](/details-term/GO:0070724). This machinery is directly linked to its primary biological process: regulating [multicellular organismal-level iron ion homeostasis](/details-term/GO:0060586). The serine protease TMPRSS6 (matriptase-2) is known to cleave membrane-bound HJV, which inhibits hepcidin activation, providing a key regulatory mechanism for this pathway [[Link](https://doi.org/10.1016/j.cmet.2008.09.012)]. Interestingly, Reactome pathways also implicate [HJV](/details-gene/148738) in [Nervous system development](/details-pathway/R-HSA-9675108) and [Axon guidance](/details-pathway/R-HSA-422475), suggesting its function as a BMP co-receptor may extend to developmental processes beyond iron metabolism. ## Research Directions The established role of [HJV](/details-gene/148738) in iron homeostasis is clear, but its functions in other tissues, such as muscle and potentially the nervous system, warrant further investigation. **Proposed Hypotheses:** 1. Given its high expression in [muscle cells](/details-cell/CL0000187) and its function in BMP signaling, [HJV](/details-gene/148738) may play a direct, local role in muscle regeneration and repair. Skeletal muscle repair is heavily dependent on BMP signaling, and HJV could act as a tissue-specific modulator of this process, independent of its systemic effects on iron. 2. The annotation for nervous system development pathways ([R-HSA-9675108](https://reactome.org/content/detail/R-HSA-9675108)) suggests that [HJV](/details-gene/148738) may have an underappreciated function in neuronal development or maintenance. Pathological iron accumulation in the brain is a feature of neurodegenerative diseases, and HJV's role in local iron or BMP signaling within the CNS could be a contributing factor. **Experimental Approach:** To test the hypothesis regarding the role of [HJV](/details-gene/148738) in muscle repair, a muscle-specific conditional knockout mouse model (e.g., MyoD-Cre; HJV-flox/flox) could be generated. These mice could then be subjected to a standardized muscle injury, such as cardiotoxin injection into the tibialis anterior muscle. The regenerative process could be compared to wild-type littermates by analyzing muscle histology (fiber cross-sectional area), quantifying satellite cell proliferation and differentiation (via Pax7 and MyoG staining), and performing functional tests to assess muscle strength recovery over time. **Therapeutic Potential:** As juvenile hemochromatosis is caused by loss-of-function mutations in [HJV](/details-gene/148738) [[Link](https://doi.org/10.1182/blood-2004-01-0192)], therapeutic strategies should aim at **activation** or restoration of the HJV-BMP-hepcidin signaling axis. A promising avenue is gene therapy, where a functional copy of the [HJV](/details-gene/148738) gene is delivered specifically to [hepatocytes](/details-cell/CL0000182) using AAV vectors. This could provide a long-term or curative treatment. Alternatively, developing small molecule agonists that mimic HJV's function by stabilizing the BMP receptor complex or promoting downstream SMAD signaling could offer a pharmacological approach to restore hepcidin production and correct systemic iron overload.

Genular Protein ID: 3800791704

Symbol: RGMC_HUMAN

Name: Hemochromatosis type 2 protein

UniProtKB Accession Codes:

Q6ZVN8 B1ALI7 Q2PQ63 Q6IMF6 Q8NAH2 Q8WVJ5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 EMBL 13 Ensembl 5 EvolutionaryTrace 1 ExpressionAtlas 1 GO 21 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 6 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14647275

Title: Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis.

PubMed ID: 14647275

DOI: 10.1038/ng1274

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 16604073

Title: Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression.

PubMed ID: 16604073

DOI: 10.1038/ng1777

PubMed ID: 18976966

Title: The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin.

PubMed ID: 18976966

DOI: 10.1016/j.cmet.2008.09.012

PubMed ID: 19357398

Title: Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia.

PubMed ID: 19357398

DOI: 10.1182/blood-2008-12-195594

PubMed ID: 25156943

Title: Functional and clinical impact of novel TMPRSS6 variants in iron-refractory iron-deficiency anemia patients and genotype-phenotype studies.

PubMed ID: 25156943

DOI: 10.1002/humu.22632

PubMed ID: 14982873

Title: Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis.

PubMed ID: 14982873

DOI: 10.1182/blood-2004-01-0192

PubMed ID: 14982867

Title: Genetic abnormalities and juvenile hemochromatosis: mutations of the HJV gene encoding hemojuvelin.

PubMed ID: 14982867

DOI: 10.1182/blood-2004-01-0072

PubMed ID: 15461631

Title: Hemojuvelin (HJV) mutations in persons of European, African-American and Asian ancestry with adult onset haemochromatosis.

PubMed ID: 15461631

DOI: 10.1111/j.1365-2141.2004.05165.x

Sequence Information:

  • Length: 426
  • Mass: 45080
  • Checksum: 031C835F9B6DC06C
  • Sequence:
    • MGEPGQSPSP RSSHGSPPTL STLTLLLLLC GHAHSQCKIL RCNAEYVSST LSLRGGGSSG 
ALRGGGGGGR GGGVGSGGLC RALRSYALCT RRTARTCRGD LAFHSAVHGI EDLMIQHNCS 
RQGPTAPPPP RGPALPGAGS GLPAPDPCDY EGRFSRLHGR PPGFLHCASF GDPHVRSFHH 
HFHTCRVQGA WPLLDNDFLF VQATSSPMAL GANATATRKL TIIFKNMQEC IDQKVYQAEV 
DNLPVAFEDG SINGGDRPGG SSLSIQTANP GNHVEIQAAY IGTTIIIRQT AGQLSFSIKV 
AEDVAMAFSA EQDLQLCVGG CPPSQRLSRS ERNRRGAITI DTARRLCKEG LPVEDAYFHS 
CVFDVLISGD PNFTVAAQAA LEDARAFLPD LEKLHLFPSD AGVPLSSATL LAPLLSGLFV 
LWLCIQ

Genular Protein ID: 2644878748

Symbol: A8K466_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K466

Database IDs:

ARBA 10 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 10 ExpressionAtlas 1 GO 4 Gene3D 1 HOGENOM 1 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 Pfam 4 PharmGKB 1 RefSeq 1 SAM 2 SMR 1 VEuPathDB 1

Sequence Information:

  • Length: 313
  • Mass: 33679
  • Checksum: 0B056ED5D92B26E6
  • Sequence:
    • MIQHNCSRQG PTAPPPPRGP ALPGAGSGLP APDPCDYEGR FSRLHGRPPG FLHCASFGDP 
HVRSFHHHFH TCRVQGAWPL LDNDFLFVQA TSSPMALGAN ATATRKLTII FKNMQECIDQ 
KVYQAEVDNL PVAFEDGSIN GGDRPGGSSL SIQTANPGNH VEIQAAYIGT TIIIRQTAGQ 
LSFSIKVAED VAMAFSAEQD LQLCVGGCPP SQRLSRSERN RRGAITIDTA RRLCKEGLPV 
EDAYFHSCVF DVLISGDPNF TVAAQAALED ARAFLPDLEK LHLFPSDAGV PLSSATLLAP 
LLSGLFVLWL CIQ