CausalSentinel

Protein Dossier — NAT1 (Arylamine N-acetyltransferase 1)

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
Bipolar disorder 0.401 0.135 0.00306 Wald ratio 1 trans NA
Transferrin 0.171 0.0617 0.00553 Wald ratio 1 trans NA
Diagnoses - main ICD10: R35 Polyuria 0.406 0.156 0.00926 Wald ratio 1 trans NA
Fractured bone site(s): Arm 0.28 0.11 0.0108 Wald ratio 1 trans NA
Melanoma 0.72 0.289 0.0127 Wald ratio 1 trans NA
Diagnoses - main ICD10: K35 Acute appendicitis 0.349 0.148 0.0181 Wald ratio 1 trans NA
Happiness -0.0397 0.0176 0.0245 Wald ratio 1 trans NA
Diagnoses - main ICD10: K43 Ventral hernia 0.347 0.155 0.0254 Wald ratio 1 trans NA
Age at menopause -0.289 0.131 0.0278 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoarthritis -0.116 0.0535 0.03 Wald ratio 1 trans NA
HOMA-B -0.0394 0.0194 0.0427 Wald ratio 1 trans NA
Fasting insulin -0.0368 0.0184 0.0455 Wald ratio 1 trans NA
…and 90 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

45 association rows across 29 traits (26 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
Bone mineral density mean 1e-300 rs145318196 1 GCST90321120 no MR -> candidate analysis
FGL1 protein levels 8e-91 rs9325827 4 GCST90469235 no MR -> candidate analysis
N-acetylputrescine levels 3e-48 rs13264304 1 GCST90103088 no MR -> candidate analysis
ASAH1 protein levels 5e-27 rs191166394 2 GCST90468373 no MR -> candidate analysis
X-15461 levels 5e-26 rs4986782 1 GCST90140450 no MR -> candidate analysis
GLIPR1 protein levels 7e-25 rs757412866 1 GCST90469357 no MR -> candidate analysis
N-acetyltaurine levels 4e-22 rs4986782 4 GCST90139488 no MR -> candidate analysis
5-acetylamino-6-formylamino-3-methyluracil levels 5e-20 rs1353039 3 GCST90102841 no MR -> candidate analysis
5-acetylamino-6-amino-3-methyluracil levels 4e-13 rs12678356 1 GCST90102840 no MR -> candidate analysis
Smoking initiation 8e-13 rs55661744 1 GCST90243985 no MR -> candidate analysis
Free Cholesterol to Cholesteryl Esters in Very Large HDL rat 4e-10 rs79540484 1 GCST90828013 no MR -> candidate analysis
Low-density lipoprotein levels (MTAG) 2e-9 rs4921893 2 GCST90179148 no MR -> candidate analysis
…and 17 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
lagophthalmos 0.517 common-variant locus no MR -> candidate analysis
liver disorder 0.482 common-variant locus no MR -> candidate analysis
abscess 0.461 common-variant locus no MR -> candidate analysis
cellulitis 0.461 common-variant locus MR: beta=0.146, p=0.297 (trans)
gangrene 0.438 common-variant locus no MR -> candidate analysis
alcohol drinking 0.383 common-variant locus no MR -> candidate analysis
stroke disorder 0.309 common-variant locus no MR -> candidate analysis
skin disorder 0.211 common-variant locus no MR -> candidate analysis
urolithiasis 0.198 common-variant locus no MR -> candidate analysis
complication 0.159 common-variant locus no MR -> candidate analysis
gastrointestinal disease 0.159 common-variant locus no MR -> candidate analysis
placenta praevia 0.128 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 11 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 20 known modulators (Sodium-dependent noradrenaline transporter)
gnomAD constraint pLI=NA, LOEUF=NA — Constraint metrics missing; LoF tolerance cannot be judged.
GWAS Catalog 51 unique SNPs / 86 rows
ClinVar 150 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance