CausalSentinel

Protein Dossier — PREP (Prolyl endopeptidase)

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
Cardioembolic stroke 0.265 0.0916 0.0038 Wald ratio 1 cis NA
Non-cancer illness code self-reported: anxiety or panic attacks -0.228 0.0802 0.0045 Wald ratio 1 cis NA
Ovarian cancer -0.108 0.0405 0.00744 Wald ratio 1 cis NA
Non-cancer illness code self-reported: sleep apnoea 0.264 0.103 0.0104 Wald ratio 1 cis NA
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis 0.219 0.0872 0.0121 Wald ratio 1 cis NA
Height -0.0221 0.00905 0.0147 Wald ratio 1 cis NA
Lung adenocarcinoma -0.175 0.0745 0.019 Wald ratio 1 cis NA
High grade serous ovarian cancer -0.11 0.048 0.0217 Wald ratio 1 cis NA
Sodium in urine 0.0156 0.00724 0.0313 Wald ratio 1 cis NA
Hip osteoarthritis 0.184 0.0859 0.0321 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vitiligo 0.577 0.273 0.0344 Wald ratio 1 cis NA
Anorexia nervosa 0.17 0.0815 0.0367 Wald ratio 1 cis NA
…and 97 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

75 association rows across 51 traits (57 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
Serum levels of protein PREP 1e-65 rs1051484 2 GCST90087854 no MR -> candidate analysis
Blood protein levels 7e-44 rs1051484 1 GCST006585 no MR -> candidate analysis
Male-pattern baldness 6e-40 rs10457129 4 GCST007020 no MR -> candidate analysis
Prolyl endopeptidase level in Chronic kidney disease with hy 3e-36 rs1051484 1 GCST90234249 no MR -> candidate analysis
Prolyl endopeptidase levels 2e-30 rs71748560 2 GCST90249088 no MR -> candidate analysis
Balding type 1 2e-27 rs17804660 1 GCST007038 no MR -> candidate analysis
JT interval 6e-25 rs2634854 1 GCST90179157 no MR -> candidate analysis
heart rate (HR, mean, inv-normal transformed) 4e-22 rs117979970 1 GCST90480666 no MR -> candidate analysis
Cough in response to angiotensin-converting enzyme inhibitor 4e-21 rs7761208 1 GCST90573176 no MR -> candidate analysis
Chronic dry cough or cough in response to angiotensin-conver 2e-20 rs7761208 1 GCST90573177 no MR -> candidate analysis
BCHE protein levels 9e-20 rs72939784 2 GCST90468429 no MR -> candidate analysis
ACE-inhibitor discontinuation 1e-19 rs12210271 1 GCST90132618 no MR -> candidate analysis
…and 39 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 269 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
response to angiotensin-converting enzyme inhibitor 0.691 common-variant locus no MR -> candidate analysis
Cough 0.641 common-variant locus no MR -> candidate analysis
androgenetic alopecia 0.619 common-variant locus no MR -> candidate analysis
Peptic ulcer 0.488 common-variant locus no MR -> candidate analysis
placental abruption 0.474 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.449 common-variant locus no MR -> candidate analysis
placenta praevia 0.448 common-variant locus no MR -> candidate analysis
preeclampsia 0.446 common-variant locus no MR -> candidate analysis
connective tissue disorder 0.428 common-variant locus no MR -> candidate analysis
alopecia 0.426 common-variant locus no MR -> candidate analysis
polycythemia 0.419 common-variant locus no MR -> candidate analysis
colorectal cancer 0.4 common-variant locus no MR -> candidate analysis
Peyronie disease 0.396 common-variant locus no MR -> candidate analysis
tooth eruption 0.361 common-variant locus no MR -> candidate analysis
facial morphology 0.359 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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 (Prolyl endopeptidase)
gnomAD constraint pLI=1, LOEUF=0.451 — LoF-INTOLERANT
GWAS Catalog 58 unique SNPs / 95 rows
ClinVar 118 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance