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

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Locus annotations

Locus 356

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
MP2K4 trans Discovery rs10127775 1:230,295,789 T/A 0.41 992 0.325 0.045 6.9×10-13 1.100 2.1×10-12 6.8×10-14
MP2K4 trans Replication rs4846913 1:230,294,715 C/A 0.40 337 -0.250 0.075 0.001 -1.110 0.001 0.001

 

Regional association plots

Dual specificity mitogen-activated protein kinase kinase 4 (MP2K4)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

Dual specificity mitogen-activated protein kinase kinase 4 (MP2K4)

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

Dual specificity mitogen-activated protein kinase kinase 4 (MP2K4)

Target (abbrv.) MP2K4
Target (full name) Dual specificity mitogen-activated protein kinase kinase 4
Somalogic ID (Sequence ID) SL007237 (5242-37_3)
Entrez Gene Symbol MAP2K4
UniProt ID P45985
UniProt Comment
  • Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.
Wiki Pathways
  • Apoptosis
  • FAS pathway and Stress induction of HSP regulation
  • IL-1 signaling pathway
  • IL-6 signaling pathway
  • Insulin Signaling
  • MAPK Cascade
  • MAPK signaling pathway
  • MicroRNAs in cardiomyocyte hypertrophy
  • Regulation of toll-like receptor signaling pathway
  • TGF beta Signaling Pathway
  • TNF alpha Signaling Pathway
  • Toll-like receptor signaling pathway
  • angiogenesis overview
  • p38 MAPK Signaling Pathway
Pathway Interaction Database
  • CD40/CD40L signaling
  • CDC42 signaling events
  • Cellular roles of Anthrax toxin
  • Ceramide signaling pathway
  • Ephrin B reverse signaling
  • ErbB1 downstream signaling
  • Fc-epsilon receptor I signaling in mast cells
  • IL6-mediated signaling events
  • JNK signaling in the CD4+ TCR pathway
  • Nephrin/Neph1 signaling in the kidney podocyte
  • PDGFR-beta signaling pathway
  • RAC1 signaling pathway
  • Regulation of Androgen receptor activity
  • Regulation of p38-alpha and p38-beta
  • RhoA signaling pathway
  • Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
  • Signaling events mediated by focal adhesion kinase
  • TRAIL signaling pathway
  • VEGFR3 signaling in lymphatic endothelium
Reactome
  • FCERI mediated MAPK activation
  • Interleukin-1 signaling
  • JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
  • Oxidative Stress Induced Senescence
  • Uptake and function of anthrax toxins
Pathway Studio
  • ADRA1A → IL6 production
  • AngiopoietinR → AP-1 signaling
  • CNR1/2 → IL1B/2/4/6/10 production
  • CannabinoidR → AP-1/EGR signaling
  • DopamineR2 → AP-1/CREB/ELK-SRF signaling
  • EDG3/5 → AP-1/ELK-SRF signaling
  • EDNRA/B → vascular motility
  • EGFR → AP-1/ATF2 signaling
  • EGFR → AP-1/CREB/ELK-SRF/MYC signaling
  • EGFR/ERBB2 → TP53 signaling
  • EctodysplasinR → AP-1 signaling
  • EndothelinRa → AP-1/CREB signaling
  • EndothelinRb → AP-1/CREB/ELK-SRF signaling
  • EphrinB → JUN signaling
  • ErythropoietinR → AP-1/CREB/MYC signaling
  • FGFR → AP-1/CREB/CREBBP/ELK-SRF/MYC signaling
  • FibronectinR → AP-1/ELK-SRF/SREBF signaling
  • FibronectinR → NF-kB signaling
  • FrizzledR → JUN/PAX2 signaling
  • GDNF → HSF1 signaling
  • GNRHR → ELK-SRF signaling
  • HGFR → AP-1/CREB/MYC signaling
  • IL1R → STAT3 signaling
  • NGFR → AP-1/CEBPB/CREB/ELK-SRF/TP53 signaling
  • NGFR → MEF signaling
  • NTRK → AP-1/CREB/ELK-SRF/MYC/SMAD3/TP53 signaling
  • Nociception-related DRD2 expression targets
  • Notch → TCF3 signaling
  • PDGFR → AP-1/MYC signaling
  • PTAFR → AP-1/ATF1/CREB/ERK-SRF signaling
  • PTGER2/3 → inflammation-related expression targets
  • Summarized nociception-related expression targets
  • T-cell receptor → ATF/CREB signaling
  • TGFBR → AP-1 signaling
  • TGFBR → ATF/GADD/MAX/TP53 signaling
  • TGFBR → CREB/ELK-SRF signaling
  • TGFBR → MEF/MYOD/MYOG signaling
  • TLR → AP-1 signaling
  • TLR4 Signaling in Leukocytes
  • TNFR → AP-1/ATF/TP53 signaling
  • TNFR → CREB/ELK-SRF signaling
  • TNFRSF1A → AP-1/ATF/TP53 signaling
  • TNFRSF1A → CREB/ELK-SRF signaling
  • TNFRSF6 → DDIT3 signaling
  • TNFRSF6 → HSF1 signaling
  • ThrombinR → AP-1/CREB/ELK-SRF/SP1 signaling
  • ThrombopoietinR → AP-1/CREB/ELK-SRF/MYC signaling
  • ThrombopoietinR → SPI1 signaling
  • Toll-like Receptors Act through MYD88-TIRAP Signaling
  • VEGFR → AP-1/CREB/MYC signaling
  • VEGFR → ATF/CREB/ELK-SRF signaling
  • VasopressinR1 → CREB/ELK-SRF/AP-1/EGR signaling
  • VasopressinR2 → CREB/ELK-SRF/AP-1/EGR signaling

All locus annotations are based on the sentinel SNP (rs10127775).
However, the sentinel SNP is not contained in SNiPA's database (1000 Genomes Project, phase 3 version 5, European population). Thus, no information about linked genes or further functional annotation is available.

 

Results from other genome-wide association studies

Trait P Study Source
HDL cholesterol 7.6×10-35 24097068 (PMID) Supplemental file
Total cholesterol 2.3×10-27 24097068 (PMID) Supplemental file
Triglycerides 2.3×10-13 20686565 (PMID) GRASP2 nonQTL
Serum metabolite network profiles 1.5×10-9 22916037 (PMID) GRASP2 metabQTL
Serum ratio of (1-myristoylglycerophosphocholine)/(glycocholate) 3.6×10-5 21886157 (PMID) GRASP2 metabQTL
HDL cholesterol change with statins 7.6×10-5 20339536 (PMID) GRASP2 nonQTL
Coronary artery disease (CAD) 4.8×10-4 23202125 (PMID) GRASP2 nonQTL
Coronary artery disease and myocardial infarction 4.8×10-4 23202125 (PMID) Supplemental file