HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 322

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
C1-Esterase Inhibitor cis Discovery rs2729354 11:57,355,970 G/A 0.20 993 0.410 0.054 8×10-14 1.100 9.1×10-14 1.1×10-13
C1-Esterase Inhibitor cis Replication rs2848630 11:57,356,907 G/A 0.19 337 0.271 0.091 0.003 1.030 0.438 0.234

 

Regional association plots

Plasma protease C1 inhibitor (C1-Esterase Inhibitor)

 

Boxplots and histograms for top associations

Plasma protease C1 inhibitor (C1-Esterase Inhibitor)

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

Plasma protease C1 inhibitor (C1-Esterase Inhibitor)

Target (abbrv.) C1-Esterase Inhibitor
Target (full name) Plasma protease C1 inhibitor
Somalogic ID (Sequence ID) SL000308 (4479-14_2)
Entrez Gene Symbol SERPING1
UniProt ID P05155
UniProt Comment
  • Activation of the C1 complex is under control of the C1-inhibitor. It forms a proteolytically inactive stoichiometric complex with the C1r or C1s proteases. May play a potentially crucial role in regulating important physiological pathways including complement activation, blood coagulation, fibrinolysis and the generation of kinins. Very efficient inhibitor of FXIIa. Inhibits chymotrypsin and kallikrein.
Wiki Pathways
  • Complement and Coagulation Cascades
Reactome
  • Intrinsic Pathway of Fibrin Clot Formation
  • Platelet degranulation

All locus annotations are based on the sentinel SNP (rs2729354) and 16 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
  • SLC43A1 solute carrier family 43 (amino acid system L transporter), member 1
  • UBE2L6 ubiquitin-conjugating enzyme E2L 6
  • SMTNL1 smoothelin-like 1
  • RPS4XP13 ribosomal protein S4X pseudogene 13
Potentially regulated genes
  • RP11-872D17.8
  • PRG2 proteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic protein)
  • CLP1 cleavage and polyadenylation factor I subunit 1
  • RTN4RL2 reticulon 4 receptor-like 2
  • YPEL4 yippee-like 4 (Drosophila)
  • SLC43A3 solute carrier family 43, member 3
  • ZDHHC5 zinc finger, DHHC-type containing 5
  • SLC43A1 solute carrier family 43 (amino acid system L transporter), member 1
eQTL genes
  • BTBD18 BTB (POZ) domain containing 18
  • TIMM10 translocase of inner mitochondrial membrane 10 homolog (yeast)
  • YPEL4 yippee-like 4 (Drosophila)
  • SMTNL1 smoothelin-like 1
  • SLC43A1 solute carrier family 43 (amino acid system L transporter), member 1
  • RN7SL605P RNA, 7SL, cytoplasmic 605, pseudogene
  • ZDHHC5 zinc finger, DHHC-type containing 5
  • SERPING1 serpin peptidase inhibitor, clade G (C1 inhibitor), member 1
  • RP11-624G17.3

 

Results from other genome-wide association studies

Trait P Study Source
Gene expression of TIMM10 in peripheral blood monocytes 0×10-324 20502693 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in blood 9.8×10-198 21829388 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (probeID ILMN_1765332) in breast tumors 4.6×10-148 22522925 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (probeID ILMN_1765332) in whole blood 4×10-128 22692066 (PMID) GRASP2 eQTL
TIMM10 gene expression 1.1×10-85 21798870 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (probeID ILMN_1765332) in temporal cortex in Alzheimer's disease cases and controls 3.2×10-74 22685416 (PMID) GRASP2 eQTL
Gene expression of TIMM10 probe [GI_6912707-S] in brain cortex with no Alzheimer's interaction 1.6×10-72 19361613 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (probeID ILMN_1765332) in cerebellum in Alzheimer's disease cases and controls 3.5×10-69 22685416 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (probeID ILMN_1765332) in temporal cortex in non-Alzheimer's disease samples 1.2×10-41 22685416 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (probeID ILMN_1765332) in cerebellum in non-Alzheimer's disease samples 4.4×10-39 22685416 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (probeID ILMN_1765332) in temporal cortex in Alzheimer's disease cases 4.2×10-30 22685416 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (probeID ILMN_1765332) in cerebellum in Alzheimer's disease cases 9×10-29 22685416 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in liver 3.1×10-27 22006096 (PMID) GRASP2 eQTL
Gene expression of TIMM10 [probe ILMN_22808] in osteoblasts treated with dexamethasone 4.1×10-27 21283786 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in Temporal cortex 3.5×10-26 20485568 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in Frontal cortex 4.6×10-25 20485568 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in Caudal pons 8×10-25 20485568 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in CEU-CHB-JPT lymphoblastoid cell lines 9.4×10-24 17873874 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in Cerebellum 1.9×10-22 20485568 (PMID) GRASP2 eQTL
Gene expression of TIMM10 [probe ILMN_22808] in osteoblasts 5.6×10-22 19654370 (PMID) GRASP2 eQTL
Gene expression of TIMM10 [probe ILMN_22808] in untreated osteoblasts 7.2×10-22 21283786 (PMID) GRASP2 eQTL
Gene expression of TIMM10 [probe 1555764_s_at] in lymphoblastoid cell lines 1.5×10-21 17873877 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (probeID ILMN_1765332) in cerebellum in Progressive Supranuclear Palsy cases 3.1×10-20 22685416 (PMID) GRASP2 eQTL
Gene expression of TIMM10 [probe 218408_at] in lymphoblastoid cell lines 2.3×10-17 17873877 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (probeID ILMN_1765332) in temporal cortex in Progressive Supranuclear Palsy cases 4.5×10-17 22685416 (PMID) GRASP2 eQTL
"Gene expression of TIMM10 [transcript NM_012456, probe A_23_P64343] in liver" 2×10-16 21637794 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in blood cells in Celiac disease 2.2×10-16 19128478 (PMID) GRASP2 eQTL
Gene expression of YPEL4 in peripheral blood monocytes 8×10-15 20502693 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (ENSG00000134809) in dendritic cells 2.1×10-14 22233810 (PMID) GRASP2 eQTL
Gene expression of TIMM10 (ENSG00000134809) in dendritic cells treated with Mycobacterium tuberculosis 6.2×10-13 22233810 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in JPT lymphoblastoid cell lines 5.1×10-10 17873874 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in normal prepouch ileum 1.7×10-9 23474282 (PMID) GRASP2 eQTL
Gene expression of SLC43A1 (probeID ILMN_1780924) in cerebellum in Alzheimer's disease cases and controls 3.1×10-9 22685416 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in Lymphoblastoid cell lines 3.6×10-8 19644074 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in T cells 1.8×10-7 19644074 (PMID) GRASP2 eQTL
Gene expression of TIMM10 in Fibroblasts 9.4×10-7 19644074 (PMID) GRASP2 eQTL
Gene expression of PSME1 in peripheral blood monocytes 1.8×10-6 20502693 (PMID) GRASP2 eQTL
cg25284762 (chr11:57267655) 1.9×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg14898332 (chr11:57249408) 3.2×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Gene expression of SLC43A1 (probeID ILMN_1780924) in cerebellum in non-Alzheimer's disease samples 4.6×10-6 22685416 (PMID) GRASP2 eQTL
Gene expression of HLA-B in peripheral blood monocytes 6.5×10-6 20502693 (PMID) GRASP2 eQTL
Gene expression of SLC43A1 in liver 1.5×10-4 18462017 (PMID) GRASP2 eQTL
Gene expression of TIMM10 [probe 3373946] in peripheral blood mononuclear cells 2.3×10-4 19222302 (PMID) GRASP2 eQTL
Gene expression of XM_166913 in liver 3.1×10-4 18462017 (PMID) GRASP2 eQTL