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

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Locus annotations

Locus 294

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
RET cis Discovery rs2795502 10:43,340,662 A/G 0.15 995 0.450 0.057 1×10-14 1.100 8.4×10-11 5.1×10-5

 

Regional association plots

Proto-oncogene tyrosine-protein kinase receptor Ret (RET)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

Proto-oncogene tyrosine-protein kinase receptor Ret (RET)

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

Proto-oncogene tyrosine-protein kinase receptor Ret (RET)

Target (abbrv.) RET
Target (full name) Proto-oncogene tyrosine-protein kinase receptor Ret
Somalogic ID (Sequence ID) SL010378 (3220-40_2)
Entrez Gene Symbol RET
UniProt ID P07949
UniProt Comment
  • Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration.
Targeted by drugs (based on IPA annotation)
  • sunitinib
  • motesanib
  • cabozantinib
  • regorafenib
  • ponatinib
  • bortezomib/sorafenib
  • dexamethasone/lenalidomide/sorafenib
  • bevacizumab/sorafenib
  • imatinib/sirolimus
  • cabozantinib/erlotinib
  • imatinib/nilotinib/pegintron
  • imatinib
  • sorafenib
  • vandetanib
Biomarker applications (based on IPA annotation)
  • efficacy
  • response to therapy
Wiki Pathways
  • SIDS Susceptibility Pathways
Pathway Interaction Database
  • Posttranslational regulation of adherens junction stability and dissassembly
  • Signaling events regulated by Ret tyrosine kinase
Pathway Studio
  • GDNF → HSF1 signaling
  • GFs/TNF → ion channels
  • Regulation of calcium flux

All locus annotations are based on the sentinel SNP (rs2795502) and 54 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
eQTL genes
  • ANKRA2 ankyrin repeat, family A (RFXANK-like), 2

 

Results from other genome-wide association studies

Trait P Study Source
cg20628663 (chr10:43360351) 3.3×10-310 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Progressive supranuclear palsy 3×10-7 21685912 (PMID) GWAS Catalog via SNiPA
cg14325778 (chr10:43375460) 3.8×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Height standard deviation scores in infancy/early childhood 1.4×10-4 20668459 (PMID) GRASP2 nonQTL
Anorexia nervosa 4.3×10-4 24514567 (PMID) Supplemental file