Locus 155

GWAS results
Target annotations
Locus annotations
Network
Remarks

Top associations per target

Target	cis/trans	Study	SNP	SNP location	Maj/min allele	MAF	N	β_inv	se_inv	P_inv	fc_log	P_log	P_raw
MP2K2	trans	Discovery	rs515863	13:113,839,747	C/T	0.17	996	-0.592	0.054	2.5×10^-26	-1.190	6.5×10^-26	9.3×10^-27
MP2K2	trans	Replication	rs515863	13:113,839,747	G/A	0.27	337	-0.464	0.078	6.2×10^-9	-1.190	4.5×10^-8	1.2×10^-8

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 (rs515863) and 5 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

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Genes hit or close-by	PROZ protein Z, vitamin K-dependent plasma glycoprotein PCID2 PCI domain containing 2 CUL4A cullin 4A
eQTL genes	RP11-120K24.4 PROZ protein Z, vitamin K-dependent plasma glycoprotein

Results from other genome-wide association studies

Trait	P	Study	Source
cg06567722 (chr13:113834307)	3.3×10^-18	10.1101/033084 (DOI)	BIOS QTL cis-meQTLs
"Gene expression of PROZ [transcript NM_003891, probe A_23_P140074] in liver"	1×10^-14	21637794 (PMID)	GRASP2 eQTL
Gene expression of PROZ in liver	7.9×10^-14	18462017 (PMID)	GRASP2 eQTL
cg10350215 (chr13:113832436)	9.5×10^-5	10.1101/033084 (DOI)	BIOS QTL cis-meQTLs

Possible link between cis-variants and protein levels of MAP2K2.

This locus harbours a replicated trans-pQTL to Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2).

The information gathered here is a result of an attempt to keep track of all interesting information that we encountered while investigating these loci. Please bear in mind that the annotation given here is neither complete nor free of errors, and that all information provided here should be confirmed by additional literature research before being used as a basis for firm conclusions or further experiments.

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

ONLINE SUPPLEMENTARY INFORMATION

Locus 155

Top associations per target

Regional association plots

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

Boxplots and histograms for top associations

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

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

Linked genes

Results from other genome-wide association studies

Possible link between cis-variants and protein levels of MAP2K2.