CausalSentinel

Protein Dossier — AKR1B1 (Aldo-keto reductase family 1 member B1)

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
Birth weight -0.055 0.0216 0.011 Wald ratio 1 cis NA
Cough on most days 0.144 0.0576 0.0125 Wald ratio 1 cis NA
Sodium in urine 0.0297 0.0126 0.0188 Wald ratio 1 cis NA
Fractured bone site(s): Other bones 0.105 0.0504 0.0379 Wald ratio 1 cis NA
Non-cancer illness code self-reported: muscle or soft tissue injuries -0.604 0.31 0.0514 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0411 0.0212 0.0525 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression 0.0926 0.0483 0.0553 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis 0.191 0.101 0.0584 Wald ratio 1 cis NA
Cancer code self-reported: small intestine or small bowel cancer 0.671 0.358 0.0609 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia 0.273 0.15 0.0691 Wald ratio 1 cis NA
Non-cancer illness code self-reported: uterine fibroids 0.161 0.089 0.0699 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine 0.12 0.0661 0.0703 Wald ratio 1 cis NA
…and 48 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

25 association rows across 17 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
AKR1B1 protein levels 2e-105 rs2229542 2 GCST90468273 no MR -> candidate analysis
Serum levels of protein AKR1B1 5e-72 rs2229542 1 GCST90090865 no MR -> candidate analysis
Aldose reductase (analyte X9854.36) levels 1e-48 rs2229542 1 GCST90427957 no MR -> candidate analysis
Aldose reductase levels 6e-29 rs796703 1 GCST90246483 no MR -> candidate analysis
Height 6e-21 rs10263438 1 GCST90245848 no MR -> candidate analysis
Aldose reductase levels (AKR1B1.9854.36.3) 5e-15 rs2229542 1 GCST90240227 no MR -> candidate analysis
Systolic blood pressure 1e-13 rs782520 4 GCST90662908 MR: beta=0.0177, p=0.177 (cis)
Diastolic blood pressure 1e-13 rs782513 3 GCST90292474 no MR -> candidate analysis
Medication use (calcium channel blockers) 7e-13 rs782507 1 GCST90018987 no MR -> candidate analysis
Protein quantitative trait loci (liver) 7e-12 rs2229542 2 GCST011427 no MR -> candidate analysis
Hypertension 1e-11 rs782513 2 GCST90292475 MR: beta=0.031, p=0.144 (cis)
Systolic blood pressure (MTAG) 4e-11 rs1790998 1 GCST90449056 no MR -> candidate analysis
…and 5 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 737 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
hypertensive disorder 0.248 common-variant locus no MR -> candidate analysis
essential hypertension 0.229 common-variant locus no MR -> candidate analysis
alopecia areata 0.134 common-variant locus no MR -> candidate analysis

Of the 3 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 4 known modulators (Aldo-keto reductase family 1 member B1)
gnomAD constraint pLI=0.00056, LOEUF=0.778 — LoF-tolerant
GWAS Catalog 30 unique SNPs / 60 rows
ClinVar 73 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance