HRG

Chr 3q27.3

histidine rich glycoprotein

Aliases:: HRGP, HPRG
MANE:: ENST00000232003.5

OMIM: 142640 ↗NCBI: 3273 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

HRG · P04196

v62025-08-01

Predicted Aligned Error matrix for HRG — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

64.8/ 100

Low

525 residues

Confidence breakdown

Very high(≥ 90)29%
Confident(70–90)20%
Low(50–70)10%
Very low(< 50)42%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Inherited bleeding disorders
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Thrombophilia with a likely monogenic cause
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency
0.71
Abnormality of refraction
0.33
thrombotic disease
0.12
hepatocellular carcinoma
0.11
neoplasm
0.10
cancer
0.08
liver cancer
0.07
clear cell renal carcinoma
0.06
breast carcinoma
0.06
breast cancer
0.06

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Histidine-rich glycoprotein

Plasma glycoprotein that binds a number of ligands such as heme, heparin, heparan sulfate, thrombospondin, plasminogen, and divalent metal ions. Binds heparin and heparin/glycosaminoglycans in a zinc-dependent manner. Binds heparan sulfate on the surface of liver, lung, kidney and heart endothelial cells. Binds to N-sulfated polysaccharide chains on the surface of liver endothelial cells. Inhibits rosette formation. Acts as an adapter protein and is implicated in regulating many processes such as immune complex and pathogen clearance, cell chemotaxis, cell adhesion, angiogenesis, coagulation and fibrinolysis. Mediates clearance of necrotic cells through enhancing the phagocytosis of necrotic cells in a heparan sulfate-dependent pathway. This process can be regulated by the presence of certain HRG ligands such as heparin and zinc ions. Binds to IgG subclasses of immunoglobins containing kappa and lambda light chains with different affinities regulating their clearance and inhibiting the formation of insoluble immune complexes. Tethers plasminogen to the cell surface. Binds T-cells and alters the cell morphology. Modulates angiogenesis by blocking the CD6-mediated antiangiongenic effect of thrombospondins, THBS1 and THBS2. Acts as a regulator of the vascular endothelial growth factor (VEGF) signaling pathway; inhibits endothelial cell motility by reducing VEGF-induced complex formation between PXN/paxillin and ILK/integrin-linked protein kinase and by promoting inhibition of VEGF-induced tyrosine phosphorylation of focal adhesion kinases and alpha-actinins in endothelial cells. Also plays a role in the regulation of tumor angiogenesis and tumor immune surveillance. Normalizes tumor vessels and promotes antitumor immunity by polarizing tumor-associated macrophages, leading to decreased tumor growth and metastasis