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WCMC

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

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Locus annotations

Locus 119

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
MP2K2 trans Discovery rs556990 13:113,845,059 C/T 0.23 997 -0.594 0.048 2.2×10-33 -1.190 1×10-32 9.1×10-31
MP2K2 trans Replication rs4907593 13:113,830,459 A/G 0.31 337 -0.126 0.078 0.104 -1.050 0.141 0.09

 

Regional association plots

Dual specificity mitogen-activated protein kinase kinase 2 (MP2K2)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

Dual specificity mitogen-activated protein kinase kinase 2 (MP2K2)

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

Dual specificity mitogen-activated protein kinase kinase 2 (MP2K2)

Target (abbrv.) MP2K2
Target (full name) Dual specificity mitogen-activated protein kinase kinase 2
Somalogic ID (Sequence ID) SL010501 (3628-3_4)
Entrez Gene Symbol MAP2K2
UniProt ID P36507
UniProt Comment
  • Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).
Targeted by drugs (based on IPA annotation)
  • selumetinib
  • trametinib
  • dabrafenib/trametinib
Wiki Pathways
  • B Cell Receptor Signaling Pathway
  • EGF/EGFR Signaling Pathway
  • EPO Receptor Signaling
  • Focal Adhesion
  • Hypothetical Network for Drug Addiction
  • IL-1 signaling pathway
  • IL-2 Signaling pathway
  • IL-5 signaling pathway
  • IL-6 signaling pathway
  • IL-7 signaling pathway
  • IL-9 signaling pathway
  • Insulin Signaling
  • Integrin-mediated cell adhesion
  • Kit receptor signaling pathway
  • Leptin signaling pathway
  • MAPK Cascade
  • MAPK signaling pathway
  • MicroRNAs in cardiomyocyte hypertrophy
  • Prolactin Signaling Pathway
  • Regulation of Actin Cytoskeleton
  • Regulation of toll-like receptor signaling pathway
  • Serotonin HTR1 Group and FOS Pathway
  • Serotonin Receptor 2 and ELK-SRF/GATA4 signaling
  • Serotonin Receptor 4/6/7 and NR3C Signaling
  • Signaling of Hepatocyte Growth Factor Receptor
  • TCR Signaling Pathway
  • TGF beta Signaling Pathway
  • Toll-like receptor signaling pathway
Pathway Interaction Database
  • CXCR3-mediated signaling events
  • Cellular roles of Anthrax toxin
  • Ceramide signaling pathway
  • Downstream signaling in naïve CD8+ T cells
  • Endothelins
  • ErbB1 downstream signaling
  • ErbB2/ErbB3 signaling events
  • Fc-epsilon receptor I signaling in mast cells
  • GMCSF-mediated signaling events
  • IL2-mediated signaling events
  • Netrin-mediated signaling events
  • Nongenotropic Androgen signaling
  • PDGFR-beta signaling pathway
  • SHP2 signaling
  • Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
  • Signaling events mediated by Stem cell factor receptor (c-Kit)
  • Signaling events mediated by VEGFR1 and VEGFR2
  • mTOR signaling pathway
Reactome
  • ERK2 activation
  • MEK activation
  • RAF phosphorylates MEK
  • Signal transduction by L1
  • Signaling by FGFR1
  • Signaling by FGFR2
  • Signaling by FGFR3
  • Signaling by FGFR4
  • Uptake and function of anthrax toxins
Pathway Studio
  • ADRA1 → prostaglandin generation
  • ADRA1 → vasoconstriction
  • ADRA1A → IL6 production
  • ADRA2C/ADRB2 → synaptic endocytosis
  • ADRA2C/ADRB2 → vasoconstriction
  • ADRB1 → prostaglandin generation
  • AGER → CREB/SP1 signaling
  • AdenosineR → AP-1 signaling
  • AdrenergicRa → ELK-SRF signaling
  • AdrenergicRa → STAT3 signaling
  • AdrenergicRb → CREB signaling
  • AdrenergicRb → STAT3 signaling
  • AngiopoietinR → AP-1 signaling
  • AngiotensinR → CREB/ELK-SRF/TP53 signaling
  • B-cell receptor → AP-1 signaling
  • BDKRB1/2 → prostaglandin generation
  • CD19 → AP-1/ELK-SRF signaling
  • CD38 → NF-kB signaling
  • CD8+ T-cell Activation
  • CHRM1 → IL2 production
  • CHRM1/2/3 → vascular motility
  • CHRNA7 → NOS1 production
  • CNR1/2 → IL1B/2/4/6/10 production
  • CannabinoidR → AP-1/EGR signaling
  • CholecystokininR → ELK-SRF signaling
  • CholinergicRm → CREB/ELK-SRF signaling
  • CholinergicRn → CREB signaling
  • DopamineR1 → CREB/ELK-SRF signaling
  • DopamineR2 → AP-1/CREB/ELK-SRF signaling
  • EDG2 → 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 → SMAD1 signaling
  • EGFR/ERBB2 → HIF1A signaling
  • EGFR/ERBB2 → TP53 signaling
  • ERBB2/3 → EP300/ETS/ETV/SP1 signaling
  • EctodysplasinR → AP-1 signaling
  • EndothelinRa → AP-1/CREB signaling
  • EndothelinRb → AP-1/CREB/ELK-SRF signaling
  • ErythropoietinR → AP-1/CREB/MYC signaling
  • ErythropoietinR → ELK-SRF/FOS signaling
  • FGFR → AP-1/CREB/CREBBP/ELK-SRF/MYC signaling
  • FGFR → RUNX2 signaling
  • FSHR → CREB/ELK-SRF/GATA4 signaling
  • FcIgER → ELK-SRF signaling
  • FibronectinR → AP-1/ELK-SRF/SREBF signaling
  • GABA(B)R → postsynaptic inhibition
  • GALR1/2/3 → POMC/NPY production
  • GDNF → HSF1 signaling
  • GHR → ELK-SRF/MYC signaling
  • GNRHR → ELK-SRF signaling
  • GRM1/5 → CREB signaling
  • GlucagonR → CREB/ELK-SRF/SP1 signaling
  • HGFR → AP-1/CREB/MYC signaling
  • HRH2/4 → IL6/10 production
  • HTR1 → IL6 production
  • HTR4/6/7 → cation channels
  • HTR5 → TNF production
  • HTR7 → IL6 production
  • ICAM1 → AP-1/CREB/ELK-SRF signaling
  • IGF1R → ELK-SRF/HIF1A/MYC/SREBF signaling
  • IL1R → NF-kB signaling
  • IL2R → ELK-SRF/MYC signaling
  • IL4R → ELK-SRF/HMGY signaling
  • IL6R → CEBP/ELK-SRF signaling
  • IL8R → CREB/EGR signaling
  • InsulinR → ELK-SRF/SREBF signaling
  • KIT → MITF signaling
  • LeptinR → ELK-SRF signaling
  • Model of T-cell Maturation
  • NCAM1 → CREB/ELK-SRF/MYC signaling
  • NGFR → AP-1/CEBPB/CREB/ELK-SRF/TP53 signaling
  • NMDA receptors → Ca2+/CREB activation/PGE2 synthesis
  • NPY1R → CRH/POMC production
  • NTRK → AP-1/CREB/ELK-SRF/MYC/SMAD3/TP53 signaling
  • Natural Killer Cell Activation
  • Natural Killer Cell Activation through C-type Lectin-like Receptors
  • Natural Killer Cell Activation through ITAM-Containing Receptors
  • Natural Killer Cell Activation through ITSM-Containing Receptors
  • NeuropeptideYR → ATF/CREB signaling
  • NeurotensinR → ELK-SRF/AP-1/EGR signaling
  • Nociception-related DRD1/5 expression targets
  • Nociception-related DRD2 expression targets
  • Nociception-related IL1B expression targets
  • Nociception-related IL6 expression targets
  • Nociception-related NTSR1 expression targets
  • Notch → TCF3 signaling
  • OPRK → pain perception
  • OpioidR → CREB/ELK-SRF/STAT3 signaling
  • OxytocinR → ELK-SRF/GATA/AP-1 signaling
  • P2RY11/13/14 → IL8/10 production
  • PDGFR → AP-1/MYC signaling
  • PECAM → SP1 signaling
  • PTAFR → AP-1/ATF1/CREB/ERK-SRF signaling
  • PTGER1/4 → vascular motility
  • PTGER2/3 → inflammation-related expression targets
  • PTGIR → IL6 production
  • PTPRC → BCL6 signaling
  • ProstaglandinFR → ATF1/ELK-SRF/CREB signaling
  • ProstaglandinIR → ATF1/ELK-SRF/CREB signaling
  • Regulation of potassium flux
  • Regulatory T-cell Differentiation
  • SELE → ELK-SRF signaling
  • SerotoninR1 → FOS signaling
  • SerotoninR2 → ELK-SRF/GATA4 signaling
  • SerotoninR4/6/7 → NR3C signaling
  • Summarized nociception-related expression targets
  • Summarized vascular motility pathway
  • T-cell Receptor Signaling
  • T-cell receptor → AP-1 signaling
  • T-cell-Dependent B-cell Activation
  • T-cell-Independent B-cell Activation
  • TNFR → AP-1/ATF/TP53 signaling
  • TNFR → CREB/ELK-SRF signaling
  • TNFRSF1A → AP-1/ATF/TP53 signaling
  • TNFRSF1A → CREB/ELK-SRF signaling
  • TNFRSF6 → HSF1 signaling
  • TachykininR → ELK-SRF signaling
  • Th1 Cell Differentiation
  • Th2 Cell Differentiation
  • ThrombinR → AP-1/CREB/ELK-SRF/SP1 signaling
  • ThrombopoietinR → AP-1/CREB/ELK-SRF/MYC signaling
  • ThrombopoietinR → SP1 signaling
  • ThromboxaneR → CREB signaling
  • UrokinaseR → ELK-SRF signaling
  • VEGFR → AP-1/CREB/MYC signaling
  • VEGFR → ATF/CREB/ELK-SRF signaling
  • VIPR → CREB/CEBP 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 (rs556990) and 78 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
  • PROZ protein Z, vitamin K-dependent plasma glycoprotein
  • ADPRHL1 ADP-ribosylhydrolase like 1
  • TMCO3 transmembrane and coiled-coil domains 3
  • ATP11A ATPase, class VI, type 11A
  • CUL4A cullin 4A
  • PCID2 PCI domain containing 2
  • ATP4B ATPase, H+/K+ exchanging, beta polypeptide
  • MCF2L MCF.2 cell line derived transforming sequence-like
  • DCUN1D2 DCN1, defective in cullin neddylation 1, domain containing 2
  • F7 coagulation factor VII (serum prothrombin conversion accelerator)
  • GRTP1 growth hormone regulated TBC protein 1
  • TFDP1 transcription factor Dp-1
eQTL genes

 

Results from other genome-wide association studies

Trait P Study Source
cg00898013 (chr13:113819049) 3.3×10-310 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg18105134 (chr13:113819124) 3.3×10-310 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg24300038 (chr13:113819332) 3.3×10-310 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg09460490 (chr13:113829381) 5.5×10-192 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg01238865 (chr13:113812935) 2.3×10-48 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg20076468 (chr13:113825757) 1.3×10-41 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg05092353 (chr13:113777037) 1.1×10-23 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg14904725 (chr13:113777069) 4.2×10-21 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg13001878 (chr13:113777008) 6.6×10-21 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg16136079 (chr13:113811714) 2.3×10-15 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg02747210 (chr13:113776893) 1.6×10-10 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg08548500 (chr13:113777184) 2.7×10-10 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg16019436 (chr13:113825848) 5.9×10-10 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg23772843 (chr13:113759885) 4.4×10-8 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg18535410 (chr13:113793244) 3.1×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg06567722 (chr13:113834307) 1.7×10-5 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Gene expression of CUL4A [probeset 232466_at] in sputum 2.4×10-5 21949713 (PMID) GRASP2 eQTL
cg03313271 (chr13:113913118) 3.5×10-5 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg01015245 (chr13:113706686) 7.3×10-5 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Height 1.4×10-4 25282103 (PMID) Supplemental file
Pubertal growth, height at age 10 (girls) and 12 (boys) 2.7×10-4 23449627 (PMID) Supplemental file