CausalSentinel

Protein Dossier — PRSS57 (Serine protease 57)

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
Eye problems or disorders: Diabetes related eye disease 0.15 0.0488 0.00212 Wald ratio 1 cis NA
Serum creatinine (eGFRcrea) 0.00451 0.00184 0.0141 Wald ratio 1 cis NA
Eye problems or disorders: Cataract 0.0551 0.0229 0.0159 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis 0.0786 0.0328 0.0166 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia -0.0902 0.0388 0.02 Wald ratio 1 cis NA
Chronic kidney disease -0.0684 0.0301 0.0227 Wald ratio 1 cis NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] -0.0864 0.0402 0.0314 Wald ratio 1 cis NA
Diagnoses - main ICD10: K35 Acute appendicitis 0.121 0.0564 0.0314 Wald ratio 1 cis NA
Pulse rate -0.0163 0.00781 0.0373 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pneumothorax 0.331 0.16 0.0392 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders -0.141 0.0696 0.0423 Wald ratio 1 cis NA
Alcohol intake frequency -0.0128 0.00653 0.0491 Wald ratio 1 cis NA
…and 81 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

13 association rows across 12 traits (12 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
Serine protease 57 levels 2e-338 rs9304936 2 GCST90249623 no MR -> candidate analysis
Bone mineral density mean 1e-300 rs36098180 1 GCST90321120 no MR -> candidate analysis
Serum levels of protein PRSS57 2e-226 rs9304936 1 GCST90090145 no MR -> candidate analysis
Blood protein levels 7e-107 rs9304936 1 GCST006585 no MR -> candidate analysis
Circulating FSTL3 levels 3e-35 rs112418024 1 GCST90860653 no MR -> candidate analysis
FSTL3 protein levels 6e-21 rs564375277 1 GCST90469272 no MR -> candidate analysis
Cerebrospinal fluid protein FSTL3 levels 4e-13 rs8105856 1 GCST90944313 no MR -> candidate analysis
Follistatin-related protein 3 levels 1e-12 rs112418024 1 GCST90247639 no MR -> candidate analysis
Parathyroid hormone protein levels (SomaScan ID:8351-17) 4e-12 rs62131274 1 GCST90438314 no MR -> candidate analysis
Free Cholesterol to Cholesteryl Esters in Large HDL ratio 7e-9 rs111492798 1 GCST90827800 no MR -> candidate analysis
Forced vital capacity (FVC) 7e-9 rs138248777 1 GCST90705071 MR: beta=-0.00256, p=0.48 (cis)
Height 6e-8 rs2057714 1 GCST90245848 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 55 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
Graves disease 0.136 common-variant locus no MR -> candidate analysis
nicotine dependence 0.134 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=8e-07, LOEUF=1.35 — LoF-tolerant
GWAS Catalog 77 unique SNPs / 153 rows
ClinVar 121 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance