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

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Locus annotations

Locus 346

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
MAPK2 cis Discovery rs6669284 1:206,890,435 G/A 0.35 996 0.326 0.044 3.9×10-13 1.110 2.1×10-11 1×10-10
MAPK2 cis Replication rs10863805 1:206,904,464 G/A 0.25 337 0.076 0.047 0.11 1.060 0.097 0.029

 

Regional association plots

MAP kinase-activated protein kinase 2 (MAPK2)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

MAP kinase-activated protein kinase 2 (MAPK2)

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

MAP kinase-activated protein kinase 2 (MAPK2)

Target (abbrv.) MAPK2
Target (full name) MAP kinase-activated protein kinase 2
Somalogic ID (Sequence ID) SL010503 (3820-68_2)
Entrez Gene Symbol MAPKAPK2
UniProt ID P49137
UniProt Comment
  • Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA0, HSF1, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.
Wiki Pathways
  • FAS pathway and Stress induction of HSP regulation
  • IL-1 signaling pathway
  • MAPK signaling pathway
  • Serotonin HTR1 Group and FOS Pathway
  • Serotonin Receptor 2 and ELK-SRF/GATA4 signaling
  • Serotonin Receptor 4/6/7 and NR3C Signaling
  • p38 MAPK Signaling Pathway
Pathway Interaction Database
  • IL2-mediated signaling events
  • Signaling events mediated by VEGFR1 and VEGFR2
  • Signaling mediated by p38-alpha and p38-beta
  • Trk receptor signaling mediated by the MAPK pathway
  • p38 signaling mediated by MAPKAP kinases
Reactome
  • Butyrate Response Factor 1 (BRF1) destabilizes mRNA
  • CREB phosphorylation
  • Oxidative Stress Induced Senescence
  • Regulation of HSF1-mediated heat shock response
  • Synthesis of Leukotrienes (LT) and Eoxins (EX)
  • Tristetraprolin (TTP) destabilizes mRNA
  • VEGFA-VEGFR2 Pathway
  • activated TAK1 mediates p38 MAPK activation
  • p38MAPK events
Pathway Studio
  • ADRA1A → IL6 production
  • AdrenergicRa → ELK-SRF signaling
  • AngiotensinR → CREB/ELK-SRF/TP53 signaling
  • CD19 → AP-1/ELK-SRF signaling
  • CHRM1 → IL2 production
  • CNR1/2 → IL1B/2/4/6/10 production
  • CannabinoidR → AP-1/EGR signaling
  • CholecystokininR → ELK-SRF signaling
  • CholinergicRm → CREB/ELK-SRF 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/CREB/ELK-SRF/MYC 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
  • FSHR → CREB/ELK-SRF/GATA4 signaling
  • FcIgER → ELK-SRF signaling
  • FibronectinR → AP-1/ELK-SRF/SREBF 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
  • HTR1 → IL6 production
  • HTR5 → TNF production
  • HTR7 → IL6 production
  • ICAM1 → AP-1/CREB/ELK-SRF signaling
  • IGF1R → ELK-SRF/HIF1A/MYC/SREBF 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
  • LeptinR → ELK-SRF signaling
  • NGFR → AP-1/CEBPB/CREB/ELK-SRF/TP53 signaling
  • NPY1R → CRH/POMC production
  • NTRK → AP-1/CREB/ELK-SRF/MYC/SMAD3/TP53 signaling
  • NeuropeptideYR → ATF/CREB signaling
  • NeurotensinR → ELK-SRF/AP-1/EGR signaling
  • Nociception-related DRD1/5 expression targets
  • Nociception-related DRD2 expression targets
  • Nociception-related NTSR1 expression targets
  • OpioidR → CREB/ELK-SRF/STAT3 signaling
  • OxytocinR → ELK-SRF/GATA/AP-1 signaling
  • P2RY11/13/14 → IL8/10 production
  • PTAFR → AP-1/ATF1/CREB/ERK-SRF signaling
  • PTGIR → IL6 production
  • ProstaglandinFR → ATF1/ELK-SRF/CREB signaling
  • ProstaglandinIR → ATF1/ELK-SRF/CREB signaling
  • SELE → ELK-SRF signaling
  • SerotoninR1 → FOS signaling
  • SerotoninR2 → ELK-SRF/GATA4 signaling
  • SerotoninR4/6/7 → NR3C signaling
  • Summarized nociception-related expression targets
  • T-cell receptor → ATF/CREB signaling
  • TGFBR → CREB/ELK-SRF signaling
  • TNFR → CREB/ELK-SRF signaling
  • TNFRSF1A → CREB/ELK-SRF signaling
  • TachykininR → ELK-SRF signaling
  • ThrombinR → AP-1/CREB/ELK-SRF/SP1 signaling
  • ThrombopoietinR → AP-1/CREB/ELK-SRF/MYC signaling
  • UrokinaseR → ELK-SRF 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 (rs6669284) and 6 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
  • MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2
Potentially regulated genes
  • IKBKE inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon
  • IL19 interleukin 19
eQTL genes
  • IL19 interleukin 19

 

Results from other genome-wide association studies

Trait P Study Source
cg25741609 (chr1:206898282) 3.5×10-32 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Ulcerative collitis 1.5×10-6 Supplemental file
Inflammatory bowel disease 2.1×10-5 Supplemental file
Serum ratio of (3-methoxytyrosine)/(biliverdin) 2.6×10-5 21886157 (PMID) GRASP2 metabQTL
Serum ratio of (levulinate (4-oxovalerate))/(phenylacetate) 2.8×10-5 21886157 (PMID) GRASP2 metabQTL