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Connecting genetic risk to disease endpoints through the human blood plasma proteome

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Locus annotations

Locus 160

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
HRG cis Discovery rs2555515 3:186,388,028 T/C 0.43 993 -0.453 0.042 2.8×10-25 -1.100 1.2×10-24 5×10-26
HRG cis Replication rs2555515 3:186,388,028 A/G 0.32 337 -0.191 0.083 0.023 -1.050 0.137 0.039

 

Regional association plots

 

Boxplots and histograms for top associations

Histidine-rich glycoprotein (HRG)

inverse-normalized probe levels log2 transformed probe levels raw probe levels
Discovery study
Replication study

Histidine-rich glycoprotein (HRG)

Target (abbrv.) HRG
Target (full name) Histidine-rich glycoprotein
Somalogic ID (Sequence ID) SL006448 (4996-66_1)
Entrez Gene Symbol HRG
UniProt ID P04196
UniProt Comment
  • 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.
Reactome
  • Dissolution of Fibrin Clot
  • Platelet degranulation

All locus annotations are based on the sentinel SNP (rs2555515) and 3 proxy variant(s) that is/are in linkage disequilibrium r2 ≥ 0.8. Linkage disequilibrium is based on data from the 1000 Genomes Project, phase 3 version 5, European population and was retrieved using SNiPA's Block Annotation feature.
Download the detailed results of SNiPA's block annotation (PDF)

Linked genes

Genes hit or close-by