CausalSentinel

Protein Dossier — UGT1A6 (UDP-glucuronosyltransferase 1A6)

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
Total cholesterol 0.086 0.014 7.18e-10 Wald ratio 1 cis NA
LDL cholesterol 0.0709 0.0147 1.43e-06 Wald ratio 1 cis NA
Thalamus volume -78.2 25.6 0.00225 Wald ratio 1 cis NA
Triglycerides 0.0377 0.0132 0.00427 Wald ratio 1 cis NA
Bipolar disorder -0.26 0.0928 0.00502 Wald ratio 1 cis NA
Diagnoses - main ICD10: K80 Cholelithiasis -0.242 0.0873 0.00562 Wald ratio 1 cis NA
Diagnoses - main ICD10: G47 Sleep disorders 0.258 0.0995 0.00942 Wald ratio 1 cis NA
Systemic lupus erythematosus 0.445 0.187 0.0173 Wald ratio 1 cis NA
Diagnoses - main ICD10: J33 Nasal polyp 0.261 0.111 0.0187 Wald ratio 1 cis NA
HOMA-IR 0.0366 0.0158 0.0209 Wald ratio 1 cis NA
Alcohol intake frequency -0.0322 0.0144 0.0258 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0981 0.0453 0.0303 Wald ratio 1 cis NA
…and 103 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

541 association rows across 229 traits (529 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
Total bilirubin levels 3e-26677 rs35754645 28 GCST90018973 no MR -> candidate analysis
Direct bilirubin levels 9e-13050 rs10929302 15 GCST90019505 no MR -> candidate analysis
Bilirubin (z,z) levels 8e-957 rs1976391 8 GCST90245127 no MR -> candidate analysis
Biliverdin levels 2e-802 rs1976391 10 GCST90245128 no MR -> candidate analysis
Bilirubin (E,E) levels 6e-774 rs1976391 7 GCST90245126 no MR -> candidate analysis
X-11530 levels 1e-542 rs1976391 6 GCST90245503 no MR -> candidate analysis
X-11522 levels 3e-541 rs1976391 4 GCST90245502 no MR -> candidate analysis
Bilirubin degradation product, C17H18N2O4 (3) levels 2e-366 rs887829 1 GCST90200703 no MR -> candidate analysis
X-16946 levels 2e-363 rs887829 4 GCST90245615 no MR -> candidate analysis
Succinimide levels 4e-333 rs887829 2 GCST90245438 no MR -> candidate analysis
Bilirubin levels 5e-324 rs6742078 20 GCST000386 no MR -> candidate analysis
Bilirubin degradation product, C16H18N2O5 (3) levels 2e-308 rs887829 1 GCST90200271 no MR -> candidate analysis
…and 217 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 234 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
Gilbert syndrome 0.763 0.28 established (curated) no MR -> candidate analysis
porphyrin metabolism disease 0.749 0.862 multi-layer: burden+GWAS (allelic-series candidate) no MR -> candidate analysis
Crigler-Najjar syndrome type 1 0.931 established (curated) no MR -> candidate analysis
Crigler-Najjar syndrome type 2 0.928 established (curated) no MR -> candidate analysis
transient familial neonatal hyperbilirubinemia 0.917 established (curated) no MR -> candidate analysis
Hyperbilirubinemia 0.73 established (curated) no MR -> candidate analysis
Crigler-Najjar syndrome 0.9 established (curated) no MR -> candidate analysis
bilirubin metabolism disease 0.708 0.775 multi-layer: burden+GWAS (allelic-series candidate) no MR -> candidate analysis
hereditary disease 0.841 established (curated) no MR -> candidate analysis
cholelithiasis 0.684 common-variant locus MR: beta=-0.242, p=0.00562 (cis)
Cholecystitis 0.533 common-variant locus no MR -> candidate analysis
Jaundice 0.487 common-variant locus no MR -> candidate analysis
liver disorder 0.484 common-variant locus no MR -> candidate analysis
gallstones 0.47 common-variant locus no MR -> candidate analysis
type 1 diabetes mellitus 0.443 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 2 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 (UDP-glucuronosyltransferase 1A6)
gnomAD constraint pLI=1.8e-08, LOEUF=0.969 — LoF-tolerant
GWAS Catalog 302 unique SNPs / 832 rows
ClinVar 639 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx 16 clinical annotations across 11 drugs

Caveats declared by the tools

Sources

Provenance