CausalSentinel

Protein Dossier — NUDT9 (ADP-ribose pyrophosphatase)

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
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 1.78 0.54 9.70e-04 Inverse variance weighted 2 cis NA
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 1.78 0.54 9.70e-04 Inverse variance weighted 2 trans NA
Diagnoses - main ICD10: K80 Cholelithiasis 0.155 0.0483 0.0013 Inverse variance weighted 2 cis NA
Diagnoses - main ICD10: K80 Cholelithiasis 0.155 0.0483 0.0013 Inverse variance weighted 2 trans NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.142 0.0456 0.00185 Inverse variance weighted 2 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.142 0.0456 0.00185 Inverse variance weighted 2 trans NA
Systemic lupus erythematosus 0.507 0.185 0.00614 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0117 0.00455 0.0101 Inverse variance weighted 2 cis NA
Forced vital capacity (FVC) -0.0117 0.00455 0.0101 Inverse variance weighted 2 trans NA
Triglycerides -0.0333 0.0144 0.0205 Inverse variance weighted 2 cis NA
Triglycerides -0.0333 0.0144 0.0205 Inverse variance weighted 2 trans NA
Mean cell haemoglobin 0.108 0.047 0.0212 Wald ratio 1 cis NA
…and 151 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

14 association rows across 10 traits (13 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
SPARCL1 protein levels 8e-106 rs186666722 4 GCST90470717 no MR -> candidate analysis
ADP-ribose pyrophosphatase, mitochondrial level in Chronic k 3e-56 rs145881573 1 GCST90239370 no MR -> candidate analysis
Serum levels of protein NUDT9 1e-42 rs9998212 1 GCST90090711 no MR -> candidate analysis
ADP-ribose pyrophosphatase, mitochondrial levels 4e-29 rs28529046 2 GCST90427824 no MR -> candidate analysis
Blood protein levels 2e-22 rs10030035 1 GCST006585 no MR -> candidate analysis
SPARC-like protein 1 levels 3e-18 rs13138404 1 GCST90162084 no MR -> candidate analysis
Congenital anomalies of urinary system (PheCode 751.2) 7e-13 rs142149836 1 GCST90651219 no MR -> candidate analysis
Intelligence (MTAG) 2e-8 rs11945232 1 GCST005316 no MR -> candidate analysis
Tinnitus 4e-8 rs115125870 1 GCST90448242 no MR -> candidate analysis
CCL4 levels 7e-6 rs9994244 1 GCST90503414 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 42 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
gout 0.703 common-variant locus no MR -> candidate analysis
Abnormality of the urinary system 0.416 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.398 common-variant locus no MR -> candidate analysis
Nephropathy 0.382 common-variant locus no MR -> candidate analysis
nephritis 0.382 common-variant locus no MR -> candidate analysis
essential hypertension 0.37 common-variant locus no MR -> candidate analysis
liver disorder 0.056 common-variant locus no MR -> candidate analysis
cirrhosis of liver 0.049 common-variant locus no MR -> candidate analysis
hepatocellular carcinoma 0.028 established (curated) no MR -> candidate analysis
liver cancer 0.031 common-variant locus no MR -> candidate analysis
intrahepatic bile duct cancer 0.031 common-variant locus no MR -> candidate analysis
Abnormality of the liver 0.031 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 12 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 (ADP-ribose pyrophosphatase, mitochondrial)
gnomAD constraint pLI=1.1e-08, LOEUF=1.02 — LoF-tolerant
GWAS Catalog 80 unique SNPs / 160 rows
ClinVar 86 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance