CausalSentinel

Protein Dossier — ADH4 (All-trans-retinol dehydrogenase [NAD(+)] ADH4)

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: B37 Candidiasis 1.14 0.261 1.21e-05 Wald ratio 1 cis NA
Platelet count 10.2 3.1 9.97e-04 Wald ratio 1 cis NA
Autism 0.499 0.183 0.00656 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypopituitarism 0.977 0.379 0.00996 Wald ratio 1 cis NA
Chronic kidney disease -0.248 0.102 0.0148 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis 0.271 0.115 0.0185 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.0341 0.0151 0.0241 Wald ratio 1 cis NA
HOMA-IR -0.0955 0.0427 0.0252 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression 0.124 0.0577 0.0321 Wald ratio 1 cis NA
Diagnoses - main ICD10: M54 Dorsalgia 0.213 0.1 0.0332 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) 0.0289 0.0137 0.0344 Wald ratio 1 cis NA
Mean platelet volume -0.0159 0.00764 0.0372 Wald ratio 1 cis NA
…and 100 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

256 association rows across 173 traits (228 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
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
ADH4 protein levels 2e-97 rs1800759 1 GCST90468244 no MR -> candidate analysis
Alkaline phosphatase (UKB data field 30610) 4e-86 rs6822348 1 GCST90468060 no MR -> candidate analysis
…and 161 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 135 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
ischemic stroke 0.425 common-variant locus MR: beta=0.0904, p=0.387 (cis)
substance-related disorder 0.424 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.422 common-variant locus no MR -> candidate analysis
venous thromboembolism 0.355 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 3 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 (All-trans-retinol dehydrogenase [NAD(+)] ADH4)
gnomAD constraint pLI=4.7e-10, LOEUF=1.19 — LoF-tolerant
GWAS Catalog 114 unique SNPs / 269 rows
ClinVar 83 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance