HRG Gene - Histidine-Rich Glycoprotein
Comprehensive genomic and proteomic analysis of HRG, a multifunctional plasma protein involved in coagulation, immunity, and angiogenesis.
Gene Information Card
| Symbol | HRG |
|---|---|
| Full Name | Histidine-Rich Glycoprotein |
| Gene Type | Protein coding |
| Chromosomal Location | 3q27.3 |
| NCBI Gene ID | 3273 ncbi.nlm.nih.gov/gene/3273 |
| Ensembl ID | ENSG00000113966 |
| UniProt ID | P04196 |
| OMIM ID | 142640 |
| HGNC ID | 5181 |
| Aliases | HPRG, HRGP, THPH11 |
Description
The HRG gene encodes histidine-rich glycoprotein (HRG), a 75 kDa plasma protein synthesized primarily in the liver. HRG is a multidomain protein that binds to a variety of ligands including heme, heparin, plasminogen, fibrinogen, and immunoglobulins. It plays critical roles in coagulation, fibrinolysis, immune complex clearance, angiogenesis, and regulation of cell adhesion. HRG deficiency is associated with thrombophilia and altered immune responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Thrombophilia due to HRG deficiency | Loss-of-function mutations reduce HRG levels, impairing anticoagulant and profibrinolytic activities, leading to increased thrombosis risk. | ClinVar, OMIM |
| Venous thromboembolism | HRG deficiency or dysfunction disrupts hemostatic balance, predisposing to deep vein thrombosis and pulmonary embolism. | ClinVar, NCBI |
| Cancer (various) | HRG modulates angiogenesis and immune surveillance; altered expression correlates with tumor progression and metastasis. | COSMIC, NCBI |
| Preeclampsia | Reduced HRG levels may contribute to endothelial dysfunction and placental ischemia. | NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Plasma (protein) | N/A | High (secreted) |
| Bone marrow | 1.2 | Low |
| Lung | 0.8 | Low |
| Kidney | 0.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.3 | Hepatocellular carcinoma cell line |
| Huh-7 | 9.8 | Hepatoma cell line |
| K-562 | 0.2 | Chronic myeloid leukemia |
| HeLa | 0.1 | Cervical carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Ter) | Nonsense | Rare | Loss of function; associated with HRG deficiency |
| c.1129G>A (p.Gly377Ser) | Missense | Rare | Reduced protein stability and secretion |
| c.1381C>T (p.Arg461Cys) | Missense | Rare | Impaired heparin binding |
| c.1666G>A (p.Gly556Arg) | Missense | Rare | Altered plasminogen binding |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg335Ter, p.Gly377Ser) lead to reduced HRG levels or impaired ligand binding, causing thrombophilia.
Gain of Function (GOF)
No gain-of-function mutations are currently documented in ClinVar or COSMIC.
Dominant Negative (DN)
No dominant-negative mutations have been reported for HRG.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Complement and coagulation cascades (KEGG: hsa04610)
• Plasminogen activating cascade
• Hemostasis (Reactome: R-HSA-109582)
Protein Summary
Histidine-rich glycoprotein (HRG) is a 507-amino-acid plasma protein with a molecular weight of approximately 75 kDa. It contains two cystatin-like domains, a histidine-rich region, and a proline-rich region. HRG binds to multiple ligands including heme, heparin, plasminogen, fibrinogen, and IgG, thereby modulating coagulation, fibrinolysis, angiogenesis, and immune complex clearance. It is primarily synthesized in the liver and circulates in plasma at concentrations of 100-150 µg/mL. HRG deficiency is linked to thrombophilia, while altered expression is observed in various cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HRG Knockout HEK293 Cell Line | EDJ-KQ2350 | Human | 3273 | Details Get a Quote |
| HRG Knockout HeLa Cell Line | EDJ-KQ53571 | Human | 3273 | Details Get a Quote |
| HRG Knockout A-549 Cell Line | EDJ-KQ62038 | Human | 3273 | Details Get a Quote |
| HRG Knockout HCT 116 Cell Line | EDJ-KQ70519 | Human | 3273 | Details Get a Quote |
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