CausalSentinel

Protein Dossier — ATP2A3 (Sarcoplasmic/endoplasmic reticulum calcium ATPase 3)

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
HDL cholesterol 0.23 0.0272 3.10e-17 Wald ratio 1 trans 0.991
Triglycerides -0.179 0.0264 1.07e-11 Wald ratio 1 trans 0.995
Mean cell volume -0.579 0.146 6.93e-05 Wald ratio 1 trans NA
Heel bone mineral density (BMD) T-score automated -0.0656 0.0169 1.04e-04 Wald ratio 1 trans NA
Red blood cell count 0.0433 0.0125 5.32e-04 Wald ratio 1 trans NA
Mean cell haemoglobin -0.181 0.0576 0.00165 Wald ratio 1 trans NA
Thyroid cancer 1.32 0.47 0.00486 Wald ratio 1 trans NA
PGC cross-disorder traits 0.189 0.0674 0.00511 Wald ratio 1 trans NA
Depressive symptoms -0.0447 0.0179 0.0124 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension -0.0585 0.0236 0.0133 Wald ratio 1 trans NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone 0.277 0.114 0.0146 Wald ratio 1 trans NA
Forced vital capacity (FVC) 0.0244 0.0107 0.0229 Wald ratio 1 trans NA
…and 113 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

17 association rows across 10 traits (9 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
Type 2 diabetes 2e-27 rs1043246 8 GCST90492734 MR: beta=0.132, p=0.0468 (trans)
Eosinophil count 4e-12 rs887387 1 GCST007065 no MR -> candidate analysis
Eosinophill percentage (UKB data field 30210) 1e-11 rs887387 1 GCST90468069 no MR -> candidate analysis
Educational attainment 4e-8 rs8068875 1 GCST90105038 no MR -> candidate analysis
Atrial fibrillation 4e-8 rs9904017 1 GCST90559230 MR: beta=-0.126, p=0.383 (trans)
Glucose homeostasis traits 3e-6 rs1006703 1 GCST002726 no MR -> candidate analysis
Oropharynx cancer and human papilloma virus 16 negative orop 5e-6 rs35334668 1 GCST90085701 no MR -> candidate analysis
Mild age-related type 2 diabetes 5e-6 rs55858476 1 GCST90026416 no MR -> candidate analysis
Stuttering 5e-6 rs114821226 1 GCST90707227 no MR -> candidate analysis
Coronary artery calcified atherosclerotic plaque (130 HU thr 9e-6 rs7501731 1 GCST005173 no MR -> candidate analysis

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

Top diseases by Open Targets association (of 215 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 0.698 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.605 common-variant locus no MR -> candidate analysis
gastroesophageal reflux disease 0.555 common-variant locus no MR -> candidate analysis
esophageal disorder 0.496 common-variant locus no MR -> candidate analysis
alcohol drinking 0.468 common-variant locus no MR -> candidate analysis
stroke disorder 0.468 common-variant locus no MR -> candidate analysis
alopecia areata 0.463 common-variant locus no MR -> candidate analysis
diaphragmatic hernia 0.404 common-variant locus MR: beta=-0.103, p=0.383 (trans)
ovarian dysfunction 0.25 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.083 common-variant locus no MR -> candidate analysis
schizophrenia 0.07 common-variant locus MR: beta=-0.0487, p=0.391 (trans)
hypothyroidism 0.068 common-variant locus MR: beta=0.0531, p=0.337 (trans)
response to statin 0.061 common-variant locus no MR -> candidate analysis
diverticular disease 0.06 common-variant locus MR: beta=-0.109, p=0.293 (trans)
diabetic retinopathy 0.054 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 11 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 (Sarcoplasmic/endoplasmic reticulum calcium ATPase 3)
gnomAD constraint pLI=2.3e-10, LOEUF=0.707 — LoF-tolerant
GWAS Catalog 67 unique SNPs / 134 rows
ClinVar 247 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance