CausalSentinel

Protein Dossier — PNLIPRP1 (Inactive pancreatic lipase-related protein 1)

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
Coronary heart disease 0.244 0.0509 1.66e-06 Wald ratio 1 trans NA
Vascular or heart problems diagnosed by doctor: Angina 0.224 0.0596 1.74e-04 Wald ratio 1 trans NA
Birth weight -0.0706 0.0194 2.83e-04 Wald ratio 1 trans NA
Ulcerative colitis -0.231 0.0681 7.01e-04 Wald ratio 1 trans NA
Myocardial infarction 0.183 0.0577 0.0015 Wald ratio 1 trans NA
Inflammatory bowel disease -0.172 0.0546 0.00167 Wald ratio 1 trans NA
Diagnoses - main ICD10: K40 Inguinal hernia -0.358 0.118 0.0024 Wald ratio 1 trans NA
Amyotrophic lateral sclerosis 0.256 0.0966 0.00797 Wald ratio 1 trans NA
Non-cancer illness code self-reported: high cholesterol 0.0843 0.033 0.0106 Wald ratio 1 trans NA
Diagnoses - main ICD10: K43 Ventral hernia 0.342 0.145 0.0183 Wald ratio 1 trans NA
Fractured bone site(s): Other bones 0.115 0.0516 0.0264 Wald ratio 1 trans NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain 0.126 0.0566 0.0265 Wald ratio 1 trans NA
…and 56 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

27 association rows across 16 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  
PNLIPRP2 protein levels 3e-58 rs45604841 11 GCST90470274 no MR -> candidate analysis  
Inactive pancreatic lipase-related protein 1 levels 5e-22 rs2915762 2 GCST90248116 no MR -> candidate analysis  
Serum levels of protein PNLIPRP1 5e-16 rs2915762 1 GCST90089537 no MR -> candidate analysis  
GLIPR1 protein levels 6e-15 rs182138940 1 GCST90469357 no MR -> candidate analysis  
Inactive pancreatic lipase-related protein 1 level in Chroni 8e-15 rs12258286 1 GCST90238373 no MR -> candidate analysis  
PNLIPRP1 protein levels 2e-12 rs186836921 1 GCST90470273 no MR -> candidate analysis  
Blood protein levels 5e-9 rs2915766 1 GCST006585 no MR -> candidate analysis  
Alzheimer’s disease or family history of Alzheimer’s disease 2e-8 rs1185918181 1 GCST90624094 no MR -> candidate analysis  
Gut microbial network clusters (Pink (at 1 year) x Household 3e-8 rs2915755 1 GCST90569317 no MR -> candidate analysis  
Vaginal microbiome MetaCyc pathway (PWY-5741 ethylmalonyl-Co 2e-7 rs3816355 1 GCST90026825 no MR -> candidate analysis
Alkenylphosphatidylethanolamine (P-18:0/22:6) levels 4e-7 rs10510024 1 GCST90024423 no MR -> candidate analysis  
Loneliness 1e-6 rs74161807 1 GCST003771 no MR -> candidate analysis  
…and 4 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 47 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
injury 0.461 common-variant locus MR: beta=0.581, p=0.179 (trans)
shoulder fracture 0.461 common-variant locus no MR -> candidate analysis
clavicle fracture 0.461 common-variant locus no MR -> candidate analysis
Hypercholesterolemia 0.096 common-variant locus MR: beta=0.0843, p=0.0106 (trans)
alcohol drinking 0.043 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.043 common-variant locus no MR -> candidate analysis
stroke disorder 0.043 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 5 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=1.1e-20, LOEUF=1.3 — LoF-tolerant
GWAS Catalog 95 unique SNPs / 190 rows
ClinVar 100 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance