CausalSentinel

Protein Dossier — ADH5 (Alcohol dehydrogenase class-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
HOMA-IR 0.0634 0.0158 6.33e-05 Wald ratio 1 cis NA
Platelet count -6.06 1.55 9.60e-05 Wald ratio 1 cis NA
Fasting insulin 0.0387 0.0127 0.00225 Wald ratio 1 cis NA
HDL cholesterol 0.056 0.0187 0.0027 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0224 0.00825 0.00653 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0212 0.00782 0.00677 Wald ratio 1 cis NA
Autism -0.287 0.111 0.00937 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.149 0.058 0.0104 Wald ratio 1 cis NA
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.594 0.234 0.011 Wald ratio 1 cis NA
Age at menopause -0.176 0.0704 0.0124 Wald ratio 1 cis NA
Total cholesterol -0.0475 0.0201 0.0179 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma 0.158 0.0681 0.0206 Wald ratio 1 cis NA
…and 106 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

161 association rows across 121 traits (141 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
ADH4/GSTA1 protein level ratio 1e-271 rs2602836 1 GCST90313191 no MR -> candidate analysis
Drinks per week 4e-259 rs29001570 1 GCST90243984 no MR -> candidate analysis
ACY1/ADH4 protein level ratio 2e-191 rs2602836 1 GCST90313161 no MR -> candidate analysis
ADH4/DCXR protein level ratio 2e-189 rs2602836 1 GCST90313190 no MR -> candidate analysis
ADH4/KRT18 protein level ratio 7e-164 rs2602836 1 GCST90313192 no MR -> candidate analysis
ADH4/SCLY protein level ratio 3e-156 rs2602836 1 GCST90313195 no MR -> candidate analysis
ADH4/RBP5 protein level ratio 3e-149 rs2602836 1 GCST90313194 no MR -> candidate analysis
ADH4/C19orf12 protein level ratio 4e-142 rs2602836 1 GCST90313188 no MR -> candidate analysis
ADH4/SORD protein level ratio 2e-133 rs2602836 1 GCST90313196 no MR -> candidate analysis
ADH4/KYNU protein level ratio 5e-128 rs2602836 1 GCST90313193 no MR -> candidate analysis
ADH4/CA5A protein level ratio 3e-117 rs2602836 1 GCST90313189 no MR -> candidate analysis
Alcohol dehydrogenase class-3 levels 3e-73 rs62325239 1 GCST90246435 no MR -> candidate analysis
…and 109 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 249 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
AMED syndrome, digenic 0.764 established (curated) no MR -> candidate analysis
Alzheimer disease 0.452 common-variant locus no MR -> candidate analysis
gout 0.387 common-variant locus MR: beta=0.146, p=0.0359 (cis)
ischemic stroke 0.205 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.193 common-variant locus no MR -> candidate analysis
substance-related disorder 0.178 common-variant locus no MR -> candidate analysis
Parkinson disease 0.152 0.152 exploratory rare-variant signal no MR -> candidate analysis
venous thromboembolism 0.144 common-variant locus no MR -> candidate analysis
alcohol abuse 0.078 common-variant locus no MR -> candidate analysis

Of the 9 rows above, 8 have no MR estimate in this resource. Across all retrieved diseases for this gene: 1 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 2 known modulators (Alcohol dehydrogenase class-3)
gnomAD constraint pLI=2.3e-09, LOEUF=1.07 — LoF-tolerant
GWAS Catalog 111 unique SNPs / 252 rows
ClinVar 76 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance