CausalSentinel

Protein Dossier — SPINT3 (Kunitz-type protease inhibitor 3)

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: hypertension -0.0232 0.00774 0.00269 Wald ratio 1 cis NA
Diagnoses - main ICD10: R35 Polyuria 0.174 0.0599 0.00376 Wald ratio 1 cis NA
Parkinson’s disease 0.199 0.0756 0.00844 Wald ratio 1 cis NA
Endometrioid ovarian cancer -0.122 0.0529 0.0209 Wald ratio 1 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter -0.102 0.0466 0.029 Wald ratio 1 cis NA
Diagnoses - main ICD10: K35 Acute appendicitis 0.12 0.0567 0.0341 Wald ratio 1 cis NA
2hr glucose 0.07 0.0331 0.0348 Wald ratio 1 cis NA
Ovarian cancer -0.0504 0.0243 0.0386 Wald ratio 1 cis NA
Height 0.0107 0.00534 0.0455 Wald ratio 1 cis NA
Cough on most days 0.0433 0.0218 0.0469 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bladder problem (not cancer) -0.133 0.0667 0.047 Wald ratio 1 cis NA
Childhood intelligence 0.046 0.0236 0.0508 Wald ratio 1 cis NA
…and 90 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

26 association rows across 21 traits (25 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
Kunitz-type protease inhibitor 3 levels 1e-155 rs6032259 2 GCST90248217 no MR -> candidate analysis
Kunitz-type protease inhibitor 3 levels (SPINT3.7926.13.3) 6e-127 rs6017591 1 GCST90241719 no MR -> candidate analysis
Serum levels of protein SPINT3 7e-118 rs6032259 1 GCST90089929 no MR -> candidate analysis
Blood protein levels 3e-76 rs13042504 1 GCST006585 no MR -> candidate analysis
SPINT3 protein levels 2e-73 rs6073773 2 GCST90470729 no MR -> candidate analysis
WFDC12 protein levels 8e-29 rs17346952 1 GCST90471073 no MR -> candidate analysis
CD40 protein levels 4e-18 rs8115500 1 GCST90468633 no MR -> candidate analysis
Kunitz-type protease inhibitor 3 level in Chronic kidney dis 8e-17 rs6032259 1 GCST90238714 no MR -> candidate analysis
Stem cell factor levels 2e-14 rs6032254 1 GCST90428432 no MR -> candidate analysis
Concentration of small HDL particles 7e-14 rs117459421 1 GCST90092951 no MR -> candidate analysis
Cholesteryl ester levels in small HDL 1e-13 rs117459421 1 GCST90092946 no MR -> candidate analysis
Saturated fatty acids levels 5e-13 rs145184355 2 GCST90502194 no MR -> candidate analysis
…and 9 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 9 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
placental retention 0.301 common-variant locus no MR -> candidate analysis
bladder exstrophy 0.195 established (curated) no MR -> candidate analysis
thyroiditis 0.035 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 3 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=0.014, LOEUF=2.79 — LoF-tolerant
GWAS Catalog 55 unique SNPs / 110 rows
ClinVar 30 records; 10 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance