CausalSentinel

Protein Dossier — PLA2R1 (Secretory phospholipase A2 receptor)

MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).

1. Published MR estimates (retrieved, not computed)

Outcome beta se p method nSNP cis/trans coloc
Age at menopause 0.0887 0.0222 6.33e-05 Wald ratio 1 cis NA
Birth weight 0.0143 0.0041 4.89e-04 Wald ratio 1 cis NA
Fractured bone site(s): Ankle -0.0732 0.0244 0.00274 Wald ratio 1 cis NA
Alcohol intake frequency 0.0117 0.00393 0.00295 Wald ratio 1 cis NA
Birth length 0.0311 0.0109 0.00414 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.0119 0.00465 0.0102 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.00863 0.00344 0.0122 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain 0.0312 0.0124 0.0123 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis -0.0223 0.0091 0.0142 Wald ratio 1 cis NA
Neo-neuroticism -0.248 0.105 0.0183 Wald ratio 1 cis NA
Neo-agreeableness 0.152 0.068 0.0254 Wald ratio 1 cis NA
Mean cell haemoglobin 0.0224 0.011 0.0413 Wald ratio 1 cis NA
…and 91 more outcomes (see JSON)              

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

96 association rows across 56 traits (90 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.

Trait best p lead SNP n assoc study MR status
Circulating LY75 levels 3e-4883 rs72957586 1 GCST90860205 no MR -> candidate analysis
Secretory phospholipase A2 receptor levels 1e-619 rs3749117 2 GCST90249610 no MR -> candidate analysis
Secretory phospholipase A2 receptor levels (PLA2R1.10916.44. 6e-500 rs3749117 2 GCST90242737 no MR -> candidate analysis
Bone mineral density mean 1e-300 rs147869749 1 GCST90321120 no MR -> candidate analysis
Serum levels of protein PLA2R1 1e-287 rs55668231 1 GCST90086499 no MR -> candidate analysis
Circulating ITGB6 levels 4e-253 rs559273359 1 GCST90860250 no MR -> candidate analysis
Blood protein levels 3e-158 rs4665141 1 GCST006585 no MR -> candidate analysis
Lymphocyte antigen 75 levels 8e-110 rs116366652 1 GCST90248352 no MR -> candidate analysis
Membranous nephropathy 5e-103 rs17831251 4 GCST010004 no MR -> candidate analysis
MRC1 protein levels 6e-99 rs35771982 1 GCST90469939 no MR -> candidate analysis
LY75 protein levels 4e-96 rs147869749 27 GCST90469822 no MR -> candidate analysis
Circulating PLAU levels (id: OID00481_OID21124) 1e-57 rs3806603 1 GCST90859841 no MR -> candidate analysis
…and 44 more traits (see JSON)          

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 394 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.

Disease genetic assoc. burden (ExWAS) causal status MR status
membranous glomerulonephritis 0.87 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.691 common-variant locus no MR -> candidate analysis
clonal hematopoiesis 0.495 common-variant locus no MR -> candidate analysis
response to COVID-19 vaccine 0.453 common-variant locus no MR -> candidate analysis
hemorrhoid 0.424 common-variant locus no MR -> candidate analysis
urolithiasis 0.419 common-variant locus no MR -> candidate analysis
gastrointestinal disease 0.419 common-variant locus no MR -> candidate analysis
alcohol drinking 0.419 common-variant locus no MR -> candidate analysis
smoking initiation 0.417 common-variant locus no MR -> candidate analysis
spondylolisthesis 0.337 common-variant locus no MR -> candidate analysis
oropharynx cancer 0.307 common-variant locus no MR -> candidate analysis
kidney disorder 0.278 established (curated) no MR -> candidate analysis
substance abuse 0.286 common-variant locus no MR -> candidate analysis
Chronic Obstructive Asthma 0.228 common-variant locus no MR -> candidate analysis
adolescent idiopathic scoliosis 0.104 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.

5. Downstream annotation (druggability & safety preview)

Layer Result
ChEMBL druggability 0 known modulators (Secretory phospholipase A2 receptor)
gnomAD constraint pLI=9.4e-43, LOEUF=0.92 — LoF-tolerant
GWAS Catalog 184 unique SNPs / 416 rows
ClinVar 248 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance