CausalSentinel

Protein Dossier — PZP (Pregnancy zone protein)

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: R55 Syncope and collapse 0.128 0.0497 0.00997 Wald ratio 1 cis NA
Iron 0.0526 0.0216 0.0149 Wald ratio 1 cis NA
Transferrin Saturation 0.0506 0.0216 0.0192 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.0943 0.0405 0.0198 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.00899 0.00436 0.0392 Wald ratio 1 cis NA
Alcohol intake frequency -0.016 0.00786 0.0413 Wald ratio 1 cis NA
Hippocampus volume 19.2 10 0.0555 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) 0.0087 0.0046 0.0586 Wald ratio 1 cis NA
HDL cholesterol 0.0196 0.0106 0.0644 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.117 0.0643 0.0679 Wald ratio 1 cis NA
Diagnoses - main ICD10: M23 Internal derangement of knee 0.0603 0.0337 0.0734 Wald ratio 1 cis NA
Cancer code self-reported: prostate cancer 0.0997 0.0565 0.0775 Wald ratio 1 cis NA
…and 100 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

25 association rows across 18 traits (22 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 PZP 7e-239 rs2277413 2 GCST90089510 no MR -> candidate analysis
Pregnancy zone protein levels 3e-163 rs3741849 2 GCST90249199 no MR -> candidate analysis
Blood protein levels 3e-135 rs7311982 2 GCST006585 no MR -> candidate analysis
Serum levels of protein NUDT16L1 4e-107 rs2277413 1 GCST90087025 no MR -> candidate analysis
Refractive error 1e-40 rs10842971 1 GCST010002 no MR -> candidate analysis
Protein syndesmos levels (NUDT16L1.12497.29.3) 3e-37 rs2277413 1 GCST90242520 no MR -> candidate analysis
PZP protein levels 4e-26 rs16918159 5 GCST90453199 no MR -> candidate analysis
Primary angle-closure glaucoma (MTAG) 6e-17 rs10842970 1 GCST90832185 no MR -> candidate analysis
HYAL1 protein levels 1e-15 rs2277413 1 GCST90469495 no MR -> candidate analysis
Spherical equivalent or myopia (age of diagnosis) 4e-12 rs7968679 1 GCST006291 no MR -> candidate analysis
Myopia 4e-12 rs7968679 1 GCST003997 no MR -> candidate analysis
CCN5 protein levels 7e-12 rs2277413 1 GCST90468591 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 155 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
myopia 0.416 common-variant locus no MR -> candidate analysis
refractive error 0.387 common-variant locus no MR -> candidate analysis
primary angle-closure glaucoma 0.369 common-variant locus no MR -> candidate analysis
Abnormality of refraction 0.288 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.266 common-variant locus no MR -> candidate analysis
upper respiratory tract disorder 0.207 common-variant locus no MR -> candidate analysis
Aganglionic megacolon 0.195 established (curated) no MR -> candidate analysis
hypertension, pregnancy-induced 0.188 common-variant locus no MR -> candidate analysis
adolescent idiopathic scoliosis 0.184 common-variant locus no MR -> candidate analysis

Of the 9 rows above, 9 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 1 known modulators (Alpha-2-macroglobulin)
gnomAD constraint pLI=4.9e-42, LOEUF=0.956 — LoF-tolerant
GWAS Catalog 78 unique SNPs / 153 rows
ClinVar 267 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance