CausalSentinel

Protein Dossier — SOD3 (Extracellular superoxide dismutase [Cu-Zn])

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
Diagnoses - main ICD10: R55 Syncope and collapse 0.213 0.054 8.10e-05 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis 0.182 0.0493 2.21e-04 Wald ratio 1 cis NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0757 0.0208 2.72e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: polio or poliomyelitis 0.462 0.156 0.00299 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0507 0.0173 0.00331 Wald ratio 1 cis NA
Fractured bone site(s): Other bones 0.0706 0.0255 0.00552 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bladder problem (not cancer) 0.184 0.0688 0.00764 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.0873 0.0373 0.0191 Wald ratio 1 cis NA
Large vessel disease 0.203 0.0867 0.0193 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pernicious anaemia 0.205 0.0952 0.0316 Wald ratio 1 cis NA
Amyotrophic lateral sclerosis 0.0959 0.0451 0.0335 Wald ratio 1 cis NA
Cardioembolic stroke 0.159 0.0765 0.0372 Wald ratio 1 cis NA
…and 95 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

23 association rows across 14 traits (20 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
Extracellular superoxide dismutase [Cu-Zn] levels 1e-413 rs1799895 5 GCST90247197 no MR -> candidate analysis
Extracellular superoxide dismutase [Cu-Zn] levels (SOD3.8463 4e-140 rs1799895 1 GCST90241133 no MR -> candidate analysis
SOD3 protein levels 6e-65 rs800442 3 GCST90470706 no MR -> candidate analysis
Blood protein levels 1e-64 rs2695234 2 GCST006585 no MR -> candidate analysis
Serum levels of protein PLBD1 5e-33 rs1799895 1 GCST90089349 no MR -> candidate analysis
Serum levels of protein LRFN1 3e-21 rs1799895 1 GCST90089916 no MR -> candidate analysis
Creatinine levels 7e-20 rs1799895 1 GCST90662902 no MR -> candidate analysis
Creatinine levels (UKB data field 30700) 2e-16 rs1799895 1 GCST90468067 no MR -> candidate analysis
Protein phosphatase 1D levels 1e-14 rs1799895 2 GCST90249079 no MR -> candidate analysis
Creatinine levels in bottom 99% of individuals by creatinine 5e-14 rs1799895 1 GCST90566733 no MR -> candidate analysis
Serum creatinine levels 2e-13 rs1799895 1 GCST90018979 no MR -> candidate analysis
Serum levels of protein VNN2 4e-13 rs1799895 1 GCST90089620 no MR -> candidate analysis
…and 2 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 485 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
alcohol drinking 0.521 common-variant locus no MR -> candidate analysis
aortic atherosclerosis 0.461 common-variant locus no MR -> candidate analysis
transient ischemic attack 0.438 common-variant locus no MR -> candidate analysis
malunion fracture 0.438 common-variant locus no MR -> candidate analysis
urolithiasis 0.438 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.348 common-variant locus no MR -> candidate analysis
bronchial disorder 0.331 common-variant locus no MR -> candidate analysis
seasonal allergic rhinitis 0.331 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.292 common-variant locus no MR -> candidate analysis

Of the 9 rows above, 9 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 (Extracellular superoxide dismutase [Cu-Zn])
gnomAD constraint pLI=0.035, LOEUF=2.93 — LoF-tolerant
GWAS Catalog 49 unique SNPs / 98 rows
ClinVar 98 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance