CausalSentinel

Protein Dossier — ALDH3A1 (Aldehyde dehydrogenase, dimeric NADP-preferring)

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
Lung adenocarcinoma -0.367 0.13 0.00469 Wald ratio 1 cis NA
Ferritin 0.105 0.0405 0.00955 Wald ratio 1 cis NA
Pallidum volume 20.8 8.2 0.011 Wald ratio 1 cis NA
Caudate volume 52.6 21 0.0121 Wald ratio 1 cis NA
Lung cancer -0.2 0.0814 0.014 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gout -0.283 0.119 0.017 Wald ratio 1 cis NA
Fracture resulting from simple fall 0.0618 0.026 0.0175 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.229 0.1 0.0228 Wald ratio 1 cis NA
Squamous cell lung cancer -0.28 0.127 0.0277 Wald ratio 1 cis NA
Alcohol intake frequency -0.0333 0.0155 0.0317 Wald ratio 1 cis NA
Cough on most days -0.13 0.0613 0.0337 Wald ratio 1 cis NA
Iron 0.09 0.043 0.0361 Wald ratio 1 cis NA
…and 98 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

24 association rows across 16 traits (23 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
Circulating ALDH3A1 levels 2e-1229 rs11204414 1 GCST90860258 no MR -> candidate analysis
ALDH3A1 protein levels 9e-307 rs12938201 6 GCST90468282 no MR -> candidate analysis
Aldehyde dehydrogenase, dimeric NADP-preferring levels 6e-41 rs887241 2 GCST90246481 no MR -> candidate analysis
Serum levels of protein ALDH3A1 2e-23 rs2108967 1 GCST90086764 no MR -> candidate analysis
Aldehyde dehydrogenase, dimeric NADP-preferring levels (ALDH 8e-21 rs887241 1 GCST90240225 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 2e-19 rs12938201 1 GCST90838669 no MR -> candidate analysis
Cerebrospinal fluid protein ALDH3A1 levels 1e-16 rs4646787 1 GCST90943022 no MR -> candidate analysis
Blood protein levels 1e-13 rs2108967 1 GCST006585 no MR -> candidate analysis
Corneal resistance factor (MTAG) 2e-12 rs4646785 1 GCST90102517 no MR -> candidate analysis
Keratoconus 9e-12 rs4646785 1 GCST90013442 no MR -> candidate analysis
Corneal resistance factor 2e-10 rs12939864 2 GCST90100568 no MR -> candidate analysis
Intraocular pressure 5e-10 rs2072327 2 GCST005580 no MR -> candidate analysis
…and 4 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 195 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
keratoconus 0.485 established (curated) no MR -> candidate analysis
blood coagulation disease 0.082 common-variant locus no MR -> candidate analysis

Of the 2 rows above, 2 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 (Aldehyde dehydrogenase, dimeric NADP-preferring)
gnomAD constraint pLI=5.2e-15, LOEUF=1.18 — LoF-tolerant
GWAS Catalog 35 unique SNPs / 70 rows
ClinVar 172 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 3 drugs

Caveats declared by the tools

Sources

Provenance