HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 185

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
sTie-2 cis Discovery rs35030851 9:27,197,486 G/T 0.05 996 0.924 0.096 4.1×10-21 1.140 1.1×10-21 1.1×10-22
sTie-2 cis Replication rs45563539 9:27,203,002 G/A 0.08 337 0.540 0.116 4.3×10-6 1.110 4.8×10-6 1.7×10-5

 

Regional association plots

Angiopoietin-1 receptor, soluble (sTie-2)

 

Boxplots and histograms for top associations

Angiopoietin-1 receptor, soluble (sTie-2)

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

Angiopoietin-1 receptor, soluble (sTie-2)

Target (abbrv.) sTie-2
Target (full name) Angiopoietin-1 receptor, soluble
Somalogic ID (Sequence ID) SL003200 (3773-15_4)
Entrez Gene Symbol TEK
UniProt ID Q02763
UniProt Comment
  • Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1.
Targeted by drugs (based on IPA annotation)
  • cabozantinib
  • regorafenib
  • ponatinib
  • cabozantinib/erlotinib
  • vandetanib
Biomarker applications (based on IPA annotation)
  • efficacy
Wiki Pathways
  • Angiogenesis
  • Wnt Signaling Pathway
  • angiogenesis overview
Pathway Interaction Database
  • Angiopoietin receptor Tie2-mediated signaling
  • SHP2 signaling
Reactome
  • Tie2 Signaling
Pathway Studio
  • AngiopoietinR → AP-1 signaling
  • AngiopoietinR → FOXO signaling
  • AngiopoietinR → STAT signaling

All locus annotations are based on the sentinel SNP (rs35030851) and 8 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
Potentially regulated genes
  • TEK TEK tyrosine kinase, endothelial

 

Results from other genome-wide association studies

Trait P Study Source
Schizophrenia 2.3×10-4 23974872 (PMID) Supplemental file