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

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Locus annotations

Locus 50

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
CPNE1 cis Discovery rs2425143 20:34,350,666 C/T 0.10 997 -1.206 0.061 3.6×10-73 -2.140 1.6×10-95 2×10-57
CPNE1 cis Replication rs12481228 20:34,218,673 G/C 0.15 337 -0.877 0.045 2.2×10-56 -2.510 6.7×10-58 2×10-32

 

Regional association plots

 

Boxplots and histograms for top associations

Copine-1 (CPNE1)

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

Copine-1 (CPNE1)

Target (abbrv.) CPNE1
Target (full name) Copine-1
Somalogic ID (Sequence ID) SL011808 (5346-24_3)
Entrez Gene Symbol CPNE1
UniProt ID Q99829
UniProt Comment
  • Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes (PubMed:14674885). Involved in the TNF-alpha receptor signaling pathway in a calcium-dependent manner (PubMed:14674885). Exhibits calcium-dependent phospholipid binding properties (PubMed:9430674, PubMed:19539605). Plays a role in neuronal progenitor cell differentiation; induces neurite outgrowth via a AKT-dependent signaling cascade and calcium-independent manner (PubMed:23263657, PubMed:25450385). May recruit target proteins to the cell membrane in a calcium-dependent manner (PubMed:12522145). May function in membrane trafficking (PubMed:9430674). Involved in TNF-alpha-induced NF-kappa-B transcriptional repression by inducing endoprotease processing of the transcription factor NF-kappa-B p65/RELA subunit (PubMed:18212740). Also induces endoprotease processing of NF-kappa-B p50/NFKB1, p52/NFKB2, RELB and REL (PubMed:18212740).
Reactome
  • Glycerophospholipid biosynthesis

All locus annotations are based on the sentinel SNP (rs2425143) and 167 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
  • FER1L4 fer-1-like family member 4, pseudogene (functional)
  • SPAG4 sperm associated antigen 4
  • CPNE1 copine I
  • RP1-309K20.6
  • RN7SKP271 RNA, 7SK small nuclear pseudogene 271
  • RNU6-759P RNA, U6 small nuclear 759, pseudogene
  • RBM12 RNA binding motif protein 12
  • NFS1 NFS1 cysteine desulfurase
  • ROMO1 reactive oxygen species modulator 1
  • RBM39 RNA binding motif protein 39
  • RPF2P1 ribosome production factor 2 homolog (S. cerevisiae) pseudogene 1
  • PHF20 PHD finger protein 20
  • COX7BP2 cytochrome c oxidase subunit VIIb pseudogene 2
  • Y_RNA
  • HIGD1AP16 HIG1 hypoxia inducible domain family, member 1A pseudogene 16
  • RNU4-40P RNA, U4 small nuclear 40, pseudogene
  • RNU6-937P RNA, U6 small nuclear 937, pseudogene
  • SCAND1 SCAN domain containing 1
  • CNBD2 cyclic nucleotide binding domain containing 2
Potentially regulated genes
eQTL genes
  • EPB41L1 erythrocyte membrane protein band 4.1-like 1
  • FER1L4 fer-1-like family member 4, pseudogene (functional)
  • RPL36P4 ribosomal protein L36 pseudogene 4
  • CPNE1 copine I
  • CEP250 centrosomal protein 250kDa
  • SCAND1 SCAN domain containing 1
  • RBM39 RNA binding motif protein 39
  • LINC00657 long intergenic non-protein coding RNA 657
  • MMP24-AS1 MMP24 antisense RNA 1
  • ERGIC3 ERGIC and golgi 3

 

Results from other genome-wide association studies

Trait P Study Source
Gene expression of CPNE1 in peripheral blood monocytes 1.4×10-157 20502693 (PMID) GRASP2 eQTL
Gene expression of RBM12 in blood 3.9×10-115 21829388 (PMID) GRASP2 eQTL
Gene expression of CPNE1 (probeID ILMN_1670841) in whole blood 8×10-68 22692066 (PMID) GRASP2 eQTL
Gene expression of CPNE1 (probeID ILMN_1670841) in breast tumors 9.1×10-54 22522925 (PMID) GRASP2 eQTL
Gene expression of CPNE1 (probeID ILMN_2307025) in breast tumors 3.1×10-50 22522925 (PMID) GRASP2 eQTL
CPNE1 gene expression 2.3×10-46 21798870 (PMID) GRASP2 eQTL
Gene expression of SCAND1 in blood 5.6×10-46 21829388 (PMID) GRASP2 eQTL
Gene expression 5.6×10-38 20881960 (PMID) GRASP2 nonQTL
cg23713742 (chr20:34202745) 8.5×10-35 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Height 2.7×10-34 25282103 (PMID) Supplemental file
Gene expression of CPNE1 [probe 206918_s_at] in lymphoblastoid cell lines 1.3×10-33 17873877 (PMID) GRASP2 eQTL
cg00719668 (chr20:34541037) 3.8×10-31 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Gene expression of CPNE1 in CEU-CHB-JPT-YRI lymphoblastoid cell lines 2.3×10-28 17873874 (PMID) GRASP2 eQTL
Gene expression of CPNE1 in CEU-CHB-JPT lymphoblastoid cell lines 3.6×10-23 17873874 (PMID) GRASP2 eQTL
Gene expression of CPNE1 [probe ILMN_6266] in osteoblasts treated with PGE2 2.6×10-20 21283786 (PMID) GRASP2 eQTL
Gene expression of CPNE1 [probe ILMN_6266] in osteoblasts treated with BMP2 7.9×10-17 21283786 (PMID) GRASP2 eQTL
Gene expression of CPNE1 in lymphoblastoid cell lines 1.4×10-16 18193047 (PMID) GRASP2 eQTL
"Gene expression of CPNE1 [transcript NM_152928, probe A_23_P218726] in liver" 2×10-16 21637794 (PMID) GRASP2 eQTL
cg07042104 (chr20:34206975) 2.6×10-16 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Gene expression of CPNE1 in liver 7.1×10-16 18462017 (PMID) GRASP2 eQTL
Gene expression of CPNE1 [probe ILMN_6266] in osteoblasts treated with dexamethasone 1.5×10-15 21283786 (PMID) GRASP2 eQTL
Gene expression of CPNE1 (ENSG00000214078) in dendritic cells treated with Mycobacterium tuberculosis 1.5×10-15 22233810 (PMID) GRASP2 eQTL
Gene expression of CPNE1 in normal prepouch ileum 4.7×10-13 23474282 (PMID) GRASP2 eQTL
Gene expression of RBM12 in Fibroblasts 8×10-13 19644074 (PMID) GRASP2 eQTL
Gene expression of CPNE1 in CEU lymphoblastoid cell lines 1.7×10-12 17873874 (PMID) GRASP2 eQTL
Gene expression of CPNE1 (ENSG00000214078) in dendritic cells 2.7×10-12 22233810 (PMID) GRASP2 eQTL
Gene expression of CPNE1 [probe ILMN_6266] in osteoblasts 5.6×10-12 19654370 (PMID) GRASP2 eQTL
Gene expression of CPNE1 [probe ILMN_6266] in untreated osteoblasts 5.6×10-12 21283786 (PMID) GRASP2 eQTL
Gene expression of RBM12 in Lymphoblastoid cell lines 6.6×10-12 19644074 (PMID) GRASP2 eQTL
Hip circumfence, adjusted for BMI 3×10-11 25673412 (PMID) Supplemental file
Differential exon level expression of CPNE1 [probe 3904125] in peripheral blood mononuclear cells 2.4×10-10 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of CPNE1 [probe 3904139] in peripheral blood mononuclear cells 1.4×10-9 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of CPNE1 [probe 3904130] in peripheral blood mononuclear cells 3.2×10-9 19222302 (PMID) GRASP2 eQTL
Gene expression of CPNE1 (probeID ILMN_2307025) in temporal cortex in Alzheimer's disease cases and controls 1×10-8 22685416 (PMID) GRASP2 eQTL
Gene expression of CPNE1 in JPT lymphoblastoid cell lines 2×10-8 17873874 (PMID) GRASP2 eQTL
Triglycerides 7.6×10-8 24097068 (PMID) Supplemental file
Differential exon level expression of CPNE1 [probe 3904131] in peripheral blood mononuclear cells 8.8×10-8 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of CPNE1 [probe 3904143] in peripheral blood mononuclear cells 1.6×10-7 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of CPNE1 [probe 3904126] in peripheral blood mononuclear cells 2.5×10-7 19222302 (PMID) GRASP2 eQTL
Gene expression of CPNE1 in CHB lymphoblastoid cell lines 9×10-7 17873874 (PMID) GRASP2 eQTL
Total cholesterol 1×10-6 20686565 (PMID) GRASP2 nonQTL
cg08161081 (chr20:34327442) 1.3×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Differential exon level expression of CPNE1 [probe 3904136] in peripheral blood mononuclear cells 2.2×10-6 19222302 (PMID) GRASP2 eQTL
Gene expression of CPNE1 (probeID ILMN_2307025) in cerebellum in Alzheimer's disease cases and controls 2.3×10-6 22685416 (PMID) GRASP2 eQTL
Differential exon level expression of CPNE1 [probe 3904122] in peripheral blood mononuclear cells 2.5×10-6 19222302 (PMID) GRASP2 eQTL
Gene expression of TMEM48 in peripheral blood monocytes 2.5×10-6 20502693 (PMID) GRASP2 eQTL
Differential exon level expression of CPNE1 [probe 3904123] in peripheral blood mononuclear cells 2.9×10-6 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of CPNE1 [probe 3904138] in peripheral blood mononuclear cells 4.1×10-6 19222302 (PMID) GRASP2 eQTL
Gene expression of FXYD1 in peripheral blood monocytes 4.8×10-6 20502693 (PMID) GRASP2 eQTL
Differential exon level expression of CPNE1 [probe 3904121] in peripheral blood mononuclear cells 6.3×10-6 19222302 (PMID) GRASP2 eQTL
Gene expression of RBM12 in T cells 6.5×10-6 19644074 (PMID) GRASP2 eQTL
Hip circumfence 9.1×10-6 25673412 (PMID) Supplemental file
Gene expression of CPNE1 [probe 3904119] in brain cortex 1.9×10-5 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of CPNE1 [probe 3904131] in brain cortex 2.4×10-5 19222302 (PMID) GRASP2 eQTL
Gene expression of CPNE1 in CD4+ lymphocytes 3.1×10-5 20833654 (PMID) GRASP2 eQTL
Differential exon level expression of CPNE1 [probe 3904139] in brain cortex 5.1×10-5 19222302 (PMID) GRASP2 eQTL
LDL cholesterol 5.9×10-5 24097068 (PMID) Supplemental file
Differential exon level expression of CPNE1 [probe 3904136] in brain cortex 6.4×10-5 19222302 (PMID) GRASP2 eQTL
Gene expression of CPNE1 [probe 3904119] in peripheral blood mononuclear cells 2.5×10-4 19222302 (PMID) GRASP2 eQTL

Near total protein ablation in minor allele homozygotes, confirmed by allele specific RNA expression analysis.

Cis-association with Copine-1 (CPNE1) – see Supplemental Figure 5 below.

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.