CausalSentinel

Protein Dossier — PPP2R3A (Serine/threonine-protein phosphatase 2A regulatory subunit B’’ subunit alpha)

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
Systolic blood pressure automated reading -0.0317 0.00938 7.33e-04 Wald ratio 1 trans NA
Forearm bone mineral density -0.2 0.06 8.48e-04 Wald ratio 1 trans NA
Forced vital capacity (FVC) 0.0223 0.00752 0.00298 Wald ratio 1 trans NA
Mean cell haemoglobin concentration -0.0308 0.013 0.0177 Wald ratio 1 trans NA
Eye problems or disorders: Glaucoma 0.147 0.0664 0.0271 Wald ratio 1 trans NA
Diastolic blood pressure automated reading -0.0206 0.00939 0.0283 Wald ratio 1 trans NA
Clear cell ovarian cancer -0.334 0.153 0.0286 Wald ratio 1 trans NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.195 0.0907 0.0317 Wald ratio 1 trans NA
Bulimia nervosa -0.0557 0.026 0.0321 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis -0.0808 0.0409 0.0486 Wald ratio 1 trans NA
Sodium in urine -0.0172 0.00902 0.0568 Wald ratio 1 trans NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast -0.154 0.0843 0.0675 Wald ratio 1 trans 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

148 association rows across 127 traits (134 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
Height 1e-300 rs13079205 2 GCST90245843 no MR -> candidate analysis
Cholesterol to Total Lipids in Very Large HDL percentage 2e-41 rs34330586 1 GCST90501295 no MR -> candidate analysis
Estimated glomerular filtration rate (creatinine, cystatin c 2e-39 rs10512987 1 GCST90428446 no MR -> candidate analysis
Estimated glomerular filtration rate (cystatin c) 7e-39 rs10512987 1 GCST90428448 no MR -> candidate analysis
PTPRS protein levels 4e-30 rs4431046 1 GCST90470387 no MR -> candidate analysis
Urea levels (UKB data field 30670) 1e-29 rs13079205 1 GCST90468108 no MR -> candidate analysis
Circulating PTPRS levels 6e-29 rs4431046 1 GCST90860481 no MR -> candidate analysis
Estimated glomerular filtration rate based on creatinine and 1e-28 rs10512987 1 GCST90566737 no MR -> candidate analysis
Fibrinogen levels or factor VII levels (pleiotropy) 2e-28 rs150213942 1 GCST90129557 no MR -> candidate analysis
Ischemic stroke or fibrinogen levels (pleiotropy) 5e-28 rs150213942 1 GCST90129553 no MR -> candidate analysis
Fibrinogen levels 2e-27 rs9840812 2 GCST003194 no MR -> candidate analysis
Blood urea nitrogen levels 4e-27 rs6793835 1 GCST90018948 no MR -> candidate analysis
…and 115 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 139 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
diabetes mellitus 0.654 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.618 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.501 common-variant locus no MR -> candidate analysis
type 1 diabetes mellitus 0.474 common-variant locus no MR -> candidate analysis
aortic stenosis 0.463 common-variant locus no MR -> candidate analysis
dyslexia 0.455 common-variant locus no MR -> candidate analysis
heart failure 0.427 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.433 common-variant locus no MR -> candidate analysis
secondary malignant neoplasm 0.428 common-variant locus no MR -> candidate analysis
myocardial ischemia 0.418 common-variant locus no MR -> candidate analysis
Cachexia 0.406 common-variant locus no MR -> candidate analysis
ulcerative colitis 0.398 common-variant locus no MR -> candidate analysis
placental retention 0.403 common-variant locus no MR -> candidate analysis
Increased total eosinophil count 0.396 common-variant locus no MR -> candidate analysis
chronic kidney disease 0.396 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=1.8e-20, LOEUF=0.901 — LoF-tolerant
GWAS Catalog 103 unique SNPs / 228 rows
ClinVar 243 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance