HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 360

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
VEGF sR3 trans Discovery rs13318932 3:98,396,350 C/T 0.10 997 0.515 0.071 8×10-13 1.120 4.8×10-13 9.5×10-13

 

Regional association plots

Vascular endothelial growth factor receptor 3 (VEGF sR3)

 

Boxplots and histograms for top associations

Vascular endothelial growth factor receptor 3 (VEGF sR3)

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

Vascular endothelial growth factor receptor 3 (VEGF sR3)

Target (abbrv.) VEGF sR3
Target (full name) Vascular endothelial growth factor receptor 3
Somalogic ID (Sequence ID) SL003322 (2358-19_2)
Entrez Gene Symbol FLT4
UniProt ID P35916
UniProt Comment
  • Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'.
Targeted by drugs (based on IPA annotation)
  • sunitinib
  • pazopanib
  • axitinib
  • CEP 7055
  • tivozanib
  • motesanib
  • telatinib
  • cabozantinib
  • nintedanib
  • regorafenib
  • bortezomib/sorafenib
  • dexamethasone/lenalidomide/sorafenib
  • bevacizumab/sorafenib
  • cabozantinib/erlotinib
  • sorafenib
  • vandetanib
Biomarker applications (based on IPA annotation)
  • diagnosis
  • disease progression
  • efficacy
  • prognosis
Pathway Interaction Database
  • VEGF and VEGFR signaling network
  • VEGFR3 signaling in lymphatic endothelium
Reactome
  • VEGF binds to VEGFR leading to receptor dimerization
Pathway Studio
  • VEGFR → AP-1/CREB/MYC signaling
  • VEGFR → ATF/CREB/ELK-SRF signaling
  • VEGFR → CTNNB signaling
  • VEGFR → FOXO3A signaling

All locus annotations are based on the sentinel SNP (rs13318932) and 1 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

eQTL genes
  • DCBLD2 discoidin, CUB and LCCL domain containing 2
  • ST3GAL6 ST3 beta-galactoside alpha-2,3-sialyltransferase 6

 

Results from other genome-wide association studies

No associations available.