CausalSentinel

Protein Dossier — XPNPEP2 (Xaa-Pro aminopeptidase 2)

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
Urate 0.16 0.0285 1.98e-08 Wald ratio 1 trans NA
Diagnoses - main ICD10: L03 Cellulitis 0.38 0.0987 1.18e-04 Wald ratio 1 trans NA
Thyroid cancer -1.66 0.455 2.54e-04 Wald ratio 1 trans NA
Serum creatinine (eGFRcrea) 0.0165 0.0046 3.35e-04 Wald ratio 1 trans NA
Transferrin -0.187 0.054 5.34e-04 Wald ratio 1 trans NA
Chronic kidney disease -0.265 0.08 9.25e-04 Wald ratio 1 trans NA
Fractured bone site(s): Wrist 0.236 0.0727 0.00115 Wald ratio 1 trans NA
Birth weight 0.063 0.0195 0.00123 Wald ratio 1 trans NA
Primary sclerosing cholangitis 0.504 0.165 0.00227 Wald ratio 1 trans NA
HOMA-IR -0.065 0.0215 0.0025 Wald ratio 1 trans NA
Diagnoses - main ICD10: R07 Pain in throat and chest -0.194 0.0698 0.00537 Wald ratio 1 trans NA
Non-cancer illness code self-reported: high cholesterol -0.103 0.0385 0.00741 Wald ratio 1 trans NA
…and 109 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

8 association rows across 8 traits (8 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
Circulating XPNPEP2 levels 9e-3826 rs4829707 1 GCST90860047 no MR -> candidate analysis
Superoxide dismutase [Mn], mitochondrial levels 4e-122 rs11096255 1 GCST90249469 no MR -> candidate analysis
Serum levels of protein SOD2 4e-80 rs11096255 1 GCST90088866 no MR -> candidate analysis
Prolylproline levels 2e-78 rs4830164 1 GCST90140334 no MR -> candidate analysis
Blood protein levels in cardiovascular risk 2e-68 rs2050011 1 GCST009731 no MR -> candidate analysis
Pro-hydroxy-pro levels 2e-25 rs4830159 1 GCST90139421 no MR -> candidate analysis
Monocyte count 3e-10 rs3747343 1 GCST90002393 no MR -> candidate analysis
Serum uric acid levels 4e-8 rs3788853 1 GCST90018977 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 100 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
acquired angioedema 0.353 established (curated) no MR -> candidate analysis
primary ovarian failure 0.195 established (curated) no MR -> candidate analysis
response to darapladib 0.039 common-variant locus no MR -> candidate analysis
Diarrhea 0.039 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 4 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 (Xaa-Pro aminopeptidase 2)
gnomAD constraint pLI=1.2e-23, LOEUF=1.32 — LoF-tolerant
GWAS Catalog 8 unique SNPs / 16 rows
ClinVar 341 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance