HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 262

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
Calcineurin cis Discovery rs17266357 4:102,721,809 T/C 0.31 997 0.368 0.045 8.7×10-16 1.120 7.6×10-14 1.1×10-14
Calcineurin cis Replication rs4699262 4:102,726,005 G/A 0.19 337 0.131 0.048 0.007 1.090 0.002 0.001

 

Regional association plots

 

Boxplots and histograms for top associations

Calcineurin

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

Calcineurin

Target (abbrv.) Calcineurin
Target (full name) Calcineurin
Somalogic ID (Sequence ID) SL003657 (4903-72_1)
Entrez Gene Symbol PPP3CAPPP3R1
UniProt ID Q08209P63098
UniProt Comment
  • Q08209: Calcium-dependent, calmodulin-stimulated protein phosphatase. Many of the substrates contain a PxIxIT motif. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.
  • P63098: Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.
Targeted by drugs (based on IPA annotation)
  • cyclosporin A
Wiki Pathways
  • Alzheimers Disease
  • Energy Metabolism
  • G Protein Signaling Pathways
  • Lymphocyte TarBase
  • MAPK signaling pathway
  • MicroRNAs in cardiomyocyte hypertrophy
  • Mitochondrial Gene Expression
  • Muscle cell TarBase
  • Physiological and Pathological Hypertrophy of the Heart
Pathway Interaction Database
  • BCR signaling pathway
  • C-MYB transcription factor network
  • Calcium signaling in the CD4+ TCR pathway
  • Downstream signaling in naïve CD8+ T cells
  • IL12 signaling mediated by STAT4
  • IL12-mediated signaling events
  • Role of Calcineurin-dependent NFAT signaling in lymphocytes
Reactome
  • CLEC7A (Dectin-1) induces NFAT activation
  • Ca2+ pathway
  • DARPP-32 events
  • FCERI mediated Ca+2 mobilization

All locus annotations are based on the sentinel SNP (rs17266357) and 48 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
  • BANK1 B-cell scaffold protein with ankyrin repeats 1
eQTL genes
  • BANK1 B-cell scaffold protein with ankyrin repeats 1

 

Results from other genome-wide association studies

Trait P Study Source
cg00332153 (chr4:102712034) 3.2×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Gene expression of BANK1 in blood 5.7×10-5 21829388 (PMID) GRASP2 eQTL
Type 1 diabetes, Rheumatoid arthritis, Crohn's disease, combined case analysis, gender differentiated 1.6×10-4 17554300 (PMID) GRASP2 nonQTL
Body mass index 1.7×10-4 25673413 (PMID) Supplemental file
Systemic lupus erythematosus (SLE) 3.2×10-4 23273568 (PMID) GRASP2 nonQTL