CausalSentinel

Protein Dossier — RNPEP (Aminopeptidase B)

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
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis 0.26 0.0828 0.0017 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.12 0.0397 0.00245 Wald ratio 1 cis NA
Non-cancer illness code self-reported: polio or poliomyelitis 0.513 0.173 0.00292 Wald ratio 1 cis NA
Knee osteoarthritis -0.257 0.0876 0.00337 Wald ratio 1 cis NA
Knee and hip osteoarthritis -0.182 0.0637 0.00421 Wald ratio 1 cis NA
Neo-extraversion 0.649 0.237 0.00615 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma 0.132 0.0535 0.0136 Wald ratio 1 cis NA
Paget’s disease -0.415 0.176 0.0184 Wald ratio 1 cis NA
Height 0.0202 0.00889 0.023 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.0636 0.0281 0.0236 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia -0.122 0.0541 0.0248 Wald ratio 1 cis NA
Fasting proinsulin -0.0458 0.0208 0.0273 Wald ratio 1 cis NA
…and 110 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

23 association rows across 18 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
Urine X-10457 levels in chronic kidney disease 5e-162 rs16849483 1 GCST90266149 no MR -> candidate analysis
Aminopeptidase B levels 7e-122 rs11810017 3 GCST90246493 no MR -> candidate analysis
BCHE protein levels 2e-84 rs12059693 1 GCST90468429 no MR -> candidate analysis
Serum levels of protein RNPEP 2e-69 rs4630172 4 GCST90086949 no MR -> candidate analysis
Urinary metabolite levels in chronic kidney disease 1e-56 rs56768485 1 GCST009733 no MR -> candidate analysis
Blood protein levels 4e-42 rs59698324 1 GCST006585 no MR -> candidate analysis
Cholinesterase levels 1e-17 rs56768485 1 GCST90247015 no MR -> candidate analysis
Butyrylcholinesterase levels 9e-16 rs4950806 1 GCST001207 no MR -> candidate analysis
Cerebrospinal fluid metabolite X-10457 levels 1e-15 rs16849483 1 GCST90318292 no MR -> candidate analysis
Metabolite peak levels (QI8492) 1e-15 rs28419585 1 GCST90178387 no MR -> candidate analysis
Aminopeptidase B level in Chronic kidney disease with hypert 1e-12 rs3820439 1 GCST90233427 no MR -> candidate analysis
Plasma prolylglycine levels in chronic kidney disease 2e-11 rs6691690 1 GCST90265874 no MR -> candidate analysis
…and 6 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 122 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
obstructive sleep apnea syndrome 0.434 common-variant locus no MR -> candidate analysis
external ear disorder 0.334 common-variant locus no MR -> candidate analysis

Of the 2 rows above, 2 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 (Aminopeptidase B)
gnomAD constraint pLI=3e-16, LOEUF=1.01 — LoF-tolerant
GWAS Catalog 73 unique SNPs / 146 rows
ClinVar 138 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance