CausalSentinel

Protein Dossier — AKR1C1 (Aldo-keto reductase family 1 member C1)

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
Height -0.0899 0.0121 9.56e-14 Wald ratio 1 cis 0.99
Weight -0.0376 0.00856 1.14e-05 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.029 0.00796 2.73e-04 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0259 0.00839 0.00207 Wald ratio 1 cis NA
Transferrin Saturation 0.119 0.0403 0.00306 Wald ratio 1 cis NA
Depressive symptoms -0.036 0.0128 0.00511 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.172 0.0624 0.0058 Wald ratio 1 cis NA
Urate -0.0616 0.0223 0.0058 Wald ratio 1 cis NA
Intracranial volume -2.07e+04 7.74e+03 0.00759 Wald ratio 1 cis NA
Diagnoses - main ICD10: K20 Oesophagitis 0.212 0.0798 0.00792 Wald ratio 1 cis NA
Transferrin -0.103 0.0411 0.0122 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis 0.0736 0.0302 0.0147 Wald ratio 1 cis NA
…and 99 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

19 association rows across 14 traits (16 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
X-17359 levels 3e-55 rs61854347 1 GCST90245633 no MR -> candidate analysis
Body size or adipose distribution (multivariate analysis) 6e-36 rs7908994 1 GCST90624105 no MR -> candidate analysis
Height 1e-33 rs7908994 1 GCST90245844 MR: beta=-0.0899, p=9.56e-14 (cis)
Body shape phenotype PC3 2e-29 rs71230207 1 GCST90832991 no MR -> candidate analysis
Aldo-keto reductase family 1 member C1 levels (AKR1C1.12618. 4e-23 rs145648894 1 GCST90240226 no MR -> candidate analysis
Waist-hip index 5e-19 rs41305661 3 GCST012228 no MR -> candidate analysis
COL9A1 protein levels 2e-17 rs56136181 1 GCST90468822 no MR -> candidate analysis
Waist-to-hip ratio adjusted for BMI 2e-16 rs41305661 2 GCST012230 no MR -> candidate analysis
Hip index 2e-12 rs41305661 2 GCST012229 no MR -> candidate analysis
Waist circumference adjusted for body mass index 8e-12 rs41305661 2 GCST012226 no MR -> candidate analysis
Bone mineral density mean 9e-11 rs76207412 1 GCST90321120 no MR -> candidate analysis
Hypopharyngeal or laryngeal cancer 1e-7 rs77045180 1 GCST010285 no MR -> candidate analysis
…and 2 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 397 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
alcohol drinking 0.621 common-variant locus no MR -> candidate analysis
Peyronie disease 0.559 common-variant locus no MR -> candidate analysis
fasciitis 0.558 common-variant locus no MR -> candidate analysis
carpal tunnel syndrome 0.431 common-variant locus no MR -> candidate analysis
atrial septal defect 0.401 common-variant locus no MR -> candidate analysis
lung abscess 0.303 common-variant locus no MR -> candidate analysis
bronchopneumonia 0.303 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 7 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 C1)
gnomAD constraint pLI=2.6e-09, LOEUF=1.06 — LoF-tolerant
GWAS Catalog 73 unique SNPs / 146 rows
ClinVar 107 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance