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

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Locus annotations

Locus 138

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
Prekallikrein cis Discovery rs1511802 4:187,150,806 T/C 0.37 996 0.476 0.041 9.1×10-29 1.080 6.3×10-24 4.1×10-28
Prekallikrein cis Replication rs2304595 4:187,172,280 G/A 0.26 337 0.391 0.078 10×10-7 1.080 1×10-5 4.7×10-6

 

Regional association plots

 

Boxplots and histograms for top associations

Plasma kallikrein (Prekallikrein)

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

Plasma kallikrein (Prekallikrein)

Target (abbrv.) Prekallikrein
Target (full name) Plasma kallikrein
Somalogic ID (Sequence ID) SL000545 (4152-58_2)
Entrez Gene Symbol KLKB1
UniProt ID P03952
UniProt Comment
  • The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin.
Targeted by drugs (based on IPA annotation)
  • aprotinin
  • ecallantide
Reactome
  • Activation of Matrix Metalloproteinases
  • Intrinsic Pathway of Fibrin Clot Formation
Pathway Studio
  • Coagulation Cascade

All locus annotations are based on the sentinel SNP (rs1511802) and 17 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
  • KLKB1 kallikrein B, plasma (Fletcher factor) 1
Potentially regulated genes
  • KLKB1 kallikrein B, plasma (Fletcher factor) 1
eQTL genes
  • F11 coagulation factor XI
  • CYP4V2 cytochrome P450, family 4, subfamily V, polypeptide 2

 

Results from other genome-wide association studies

Trait P Study Source
bradykinin, des-arg(9) 8.2×10-33 24816252 (PMID) gwas.eu via SNiPA
Activated partial thromboplastin time 2.9×10-11 22703881 (PMID) GRASP2 nonQTL
Differential exon level expression of CYP4V2 [probe 2755085] in brain cortex 3.8×10-6 19222302 (PMID) GRASP2 eQTL
Gene expression of CYP4V2 in blood 2.7×10-5 21829388 (PMID) GRASP2 eQTL

Part of multiple cis/trans associations that involve proteins from vasodilatory and blood-coagulation pathways.

This locus harbours a replicated cis-pQTLs with Plasma kallikrein (KLKB1). rs1511802 also associates with bradykinin in Shin et al. [PubMed] (p=4.27×10-28, see http://www.gwas.eu). See Locus 96 for more details.

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.