CausalSentinel

Protein Dossier — SPINK1 (Serine protease inhibitor Kazal-type 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
Non-cancer illness code self-reported: diverticular disease or diverticulitis -0.563 0.2 0.00489 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.174 0.0623 0.00533 Wald ratio 1 cis NA
Forearm bone mineral density -0.182 0.0735 0.0133 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vitiligo 0.834 0.346 0.0159 Wald ratio 1 cis NA
Cigarettes smoked per day 0.923 0.392 0.0185 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.0934 0.0431 0.0302 Wald ratio 1 cis NA
Ovarian cancer 0.136 0.0637 0.0333 Wald ratio 1 cis NA
Triglycerides 0.0462 0.0222 0.0371 Wald ratio 1 cis NA
Fractured bone site(s): Other bones -0.116 0.0563 0.0397 Wald ratio 1 cis NA
Bulimia nervosa 0.066 0.033 0.0455 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] -0.201 0.102 0.0495 Wald ratio 1 cis NA
Birth length -0.0882 0.0453 0.0514 Wald ratio 1 cis NA
…and 84 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

51 association rows across 30 traits (40 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
Circulating SPINK1 levels 7e-854 rs6580502 5 GCST90860600 no MR -> candidate analysis
Circulating SCGB3A2 levels 9e-327 rs17717320 3 GCST90859981 no MR -> candidate analysis
SPINK1/TFF3 protein level ratio 1e-301 rs4705209 1 GCST90315876 no MR -> candidate analysis
SCGB3A2 protein levels 1e-236 rs17717320 2 GCST90470543 no MR -> candidate analysis
SPINK1 protein levels 8e-150 rs550228048 7 GCST90470721 no MR -> candidate analysis
Non-alcoholic chronic pancreatitis 7e-47 rs17107296 1 GCST90104595 no MR -> candidate analysis
Serum levels of protein SPINK1 3e-31 rs3777126 1 GCST90090073 no MR -> candidate analysis
Acute pancreatitis 2e-29 rs150261364 3 GCST90255375 no MR -> candidate analysis
Serine protease inhibitor Kazal-type 1 levels 9e-20 rs3777125 1 GCST90249630 no MR -> candidate analysis
Blood protein levels 2e-17 rs4705205 2 GCST006585 no MR -> candidate analysis
Chronic pancreatitis (PheCode 577.2) 2e-17 rs148911734 1 GCST90480358 no MR -> candidate analysis
Alcoholic chronic pancreatitis 3e-15 rs146437551 1 GCST004860 no MR -> candidate analysis
…and 18 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 559 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
hereditary chronic pancreatitis 0.902 established (curated) no MR -> candidate analysis
chronic pancreatitis 0.82 established (curated) no MR -> candidate analysis
acute pancreatitis 0.807 common-variant locus no MR -> candidate analysis
pancreas disorder 0.758 common-variant locus no MR -> candidate analysis
pancreatitis 0.595 established (curated) no MR -> candidate analysis
alcoholic pancreatitis 0.695 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.547 established (curated) no MR -> candidate analysis
non-alcoholic pancreatitis 0.447 common-variant locus no MR -> candidate analysis

Of the 8 rows above, 8 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=0.11, LOEUF=1.1 — LoF-tolerant
GWAS Catalog 67 unique SNPs / 123 rows
ClinVar 273 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance