Protein Dossier — AKR1A1 (Aldo-keto reductase family 1 member A1)
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 |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.033 |
0.0108 |
0.00237 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux |
0.0549 |
0.0198 |
0.00557 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.035 |
0.0128 |
0.00624 |
Wald ratio |
1 |
cis |
NA |
| High grade serous ovarian cancer |
0.0708 |
0.0286 |
0.0132 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K57 Diverticular disease of intestine |
0.0691 |
0.0285 |
0.0154 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I84 Haemorrhoids |
-0.0696 |
0.0299 |
0.02 |
Wald ratio |
1 |
cis |
NA |
| Nucleus accumbens volume |
-4.5 |
2 |
0.0246 |
Wald ratio |
1 |
cis |
NA |
| Ovarian cancer |
0.0519 |
0.024 |
0.0303 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: J33 Nasal polyp |
-0.161 |
0.0746 |
0.0306 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hiatus hernia |
-0.0584 |
0.0302 |
0.0533 |
Wald ratio |
1 |
cis |
NA |
| Fracture resulting from simple fall |
-0.0224 |
0.0119 |
0.0592 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: arthritis (nos) |
-0.103 |
0.0556 |
0.0647 |
Wald ratio |
1 |
cis |
NA |
| …and 68 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4192_10_2 |
AK1A1 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
48 association rows across 35 traits (46 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 |
| Ribitol levels |
2e-123 |
rs2229540 |
1 |
GCST90139610 |
no MR -> candidate analysis |
| Alcohol dehydrogenase [NADP(+)] levels |
5e-68 |
rs2229540 |
2 |
GCST90162010 |
no MR -> candidate analysis |
| Erythritol levels |
4e-64 |
rs2229540 |
3 |
GCST90245187 |
no MR -> candidate analysis |
| Height |
4e-50 |
rs518365 |
3 |
GCST90245848 |
no MR -> candidate analysis |
| Peroxiredoxin-1 levels |
2e-48 |
rs2356552 |
1 |
GCST90248961 |
no MR -> candidate analysis |
| platelet count (mean, inv-norm transformed) |
5e-39 |
rs11211137 |
1 |
GCST90480651 |
no MR -> candidate analysis |
| platelet count (maximum, inv-norm transformed) |
3e-34 |
rs11211137 |
1 |
GCST90480650 |
no MR -> candidate analysis |
| Urine ribitol levels in chronic kidney disease |
1e-31 |
rs2229540 |
1 |
GCST90265910 |
no MR -> candidate analysis |
| Creatinine levels |
2e-27 |
rs35349030 |
3 |
GCST90662902 |
no MR -> candidate analysis |
| Circulating PRDX1 levels |
6e-25 |
rs2356552 |
1 |
GCST90860183 |
no MR -> candidate analysis |
| Estimated glomerular filtration rate (creatinine) |
1e-24 |
rs499600 |
1 |
GCST90100220 |
no MR -> candidate analysis |
| PRDX1 protein levels |
1e-23 |
rs2356552 |
2 |
GCST90470315 |
no MR -> candidate analysis |
| …and 23 more traits (see JSON) |
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4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 551 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 |
| heart failure |
0.211 |
— |
common-variant locus |
no MR -> candidate analysis |
| deep vein thrombosis |
0.119 |
— |
common-variant locus |
no MR -> candidate analysis |
| Arthralgia |
0.081 |
— |
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 |
0 known modulators (Aldo-keto reductase family 1 member A1) |
| gnomAD constraint |
pLI=2.2e-06, LOEUF=0.921 — LoF-tolerant |
| GWAS Catalog |
87 unique SNPs / 173 rows |
| ClinVar |
69 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 551 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘AKR1A1’ and resolved to ‘Aldo-keto reductase family 1 member A1’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 69 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 35 traits by best p-value, aggregated from 48 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/P14550 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000117448/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2246/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/AKR1A1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/AKR1A1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=AKR1A1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/AKR1A1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T00:59:41 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none