CausalSentinel

Protein Dossier — NUDT12 (NAD-capped RNA hydrolase NUDT12)

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
Heel bone mineral density (BMD) T-score automated 0.033 0.0116 0.0044 Wald ratio 1 cis NA
Pallidum volume -19.5 7.51 0.00927 Wald ratio 1 cis NA
Cancer code self-reported: prostate cancer 0.219 0.0848 0.0098 Wald ratio 1 cis NA
Potassium in urine 0.0231 0.00908 0.0111 Wald ratio 1 cis NA
Diagnoses - main ICD10: B37 Candidiasis 0.62 0.247 0.012 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0347 0.0149 0.0201 Wald ratio 1 cis NA
Diagnoses - main ICD10: I30 Acute pericarditis 0.656 0.293 0.0252 Wald ratio 1 cis NA
Body mass index (BMI) 0.0195 0.00895 0.0296 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities -0.157 0.0736 0.0328 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter -0.315 0.15 0.0358 Wald ratio 1 cis NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.138 0.0678 0.0425 Wald ratio 1 cis NA
Non-cancer illness code self-reported: joint disorder 0.208 0.108 0.0534 Wald ratio 1 cis NA
…and 67 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

49 association rows across 43 traits (20 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 4e-89 rs116356771 2 GCST90321120 no MR -> candidate analysis
PAM protein levels 3e-50 rs10477828 3 GCST90470156 no MR -> candidate analysis
Peroxisomal NADH pyrophosphatase NUDT12 levels (NUDT12.13947 3e-28 rs74692061 1 GCST90242234 no MR -> candidate analysis
GLIPR1 protein levels 9e-22 rs567725349 2 GCST90469357 no MR -> candidate analysis
Type 2 diabetes 1e-20 rs186327337 3 GCST90132184 no MR -> candidate analysis
Smoking initiation 1e-14 rs2059067 1 GCST90243985 no MR -> candidate analysis
Vertex-wise sulcal depth 2e-10 rs76430606 1 GCST90095129 no MR -> candidate analysis
Gut microbial network clusters (Pink (at 1 year) x Any Breas 3e-9 rs7705390 1 GCST90569309 no MR -> candidate analysis
Total PHF-tau (SNP x SNP interaction) 3e-9 rs2396192 x rs17393709 1 GCST010340 no MR -> candidate analysis
Anatomical abnormatilies of kidney and ureters (PheCode 586. 9e-9 rs186637459 1 GCST90651455 no MR -> candidate analysis
T1 CAT volume R FrontalOrbitalCortex 1e-8 rs189668446 1 GCST90384065 no MR -> candidate analysis
Back pain 2e-8 rs4703253 1 GCST90245851 no MR -> candidate analysis
…and 31 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 70 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
Back pain 0.552 common-variant locus no MR -> candidate analysis
alcohol drinking 0.515 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.492 common-variant locus no MR -> candidate analysis
crush injury 0.461 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.432 common-variant locus no MR -> candidate analysis
placental abruption 0.419 common-variant locus no MR -> candidate analysis
stroke disorder 0.419 common-variant locus no MR -> candidate analysis
major depressive disorder 0.406 common-variant locus no MR -> candidate analysis
smoking initiation 0.406 common-variant locus no MR -> candidate analysis
dysthymic disorder 0.406 common-variant locus no MR -> candidate analysis
gastritis 0.406 common-variant locus MR: beta=0.0523, p=0.343 (cis)
thyroiditis 0.4 common-variant locus no MR -> candidate analysis
heart disorder 0.396 common-variant locus no MR -> candidate analysis
placenta praevia 0.388 common-variant locus no MR -> candidate analysis
urolithiasis 0.382 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), 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=9e-14, LOEUF=1.19 — LoF-tolerant
GWAS Catalog 56 unique SNPs / 99 rows
ClinVar 105 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance