Protein Dossier — SPINT2 (Kunitz-type protease inhibitor 2)
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: C61 Malignant neoplasm of prostate |
0.106 |
0.0308 |
5.99e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: bladder problem (not cancer) |
0.0936 |
0.0333 |
0.00489 |
Wald ratio |
1 |
cis |
NA |
| Platelet count |
-1.29 |
0.466 |
0.00555 |
Wald ratio |
1 |
cis |
NA |
| Mean platelet volume |
0.00333 |
0.00121 |
0.00596 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K57 Diverticular disease of intestine |
0.0506 |
0.0186 |
0.00659 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: prostate cancer |
0.0666 |
0.0305 |
0.029 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R35 Polyuria |
0.0881 |
0.0409 |
0.0311 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: deep venous thrombosis (dvt) |
0.0394 |
0.019 |
0.0379 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypertension |
0.00971 |
0.0047 |
0.0388 |
Wald ratio |
1 |
cis |
NA |
| Systolic blood pressure automated reading |
0.00582 |
0.00285 |
0.0412 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: N40 Hyperplasia of prostate |
0.0549 |
0.0274 |
0.0456 |
Wald ratio |
1 |
cis |
NA |
| Vascular or heart problems diagnosed by doctor: Angina |
-0.0322 |
0.0161 |
0.046 |
Wald ratio |
1 |
cis |
NA |
| …and 106 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2843_13_2 |
SPINT2 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
91 association rows across 50 traits (77 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 |
| Bone mineral density mean |
1e-300 |
rs73037316 |
2 |
GCST90321120 |
no MR -> candidate analysis |
| CDSN protein levels |
2e-156 |
rs7253823 |
1 |
GCST90468688 |
no MR -> candidate analysis |
| Serum levels of protein SPINT2 |
7e-143 |
rs11548457 |
1 |
GCST90088100 |
no MR -> candidate analysis |
| WFDC12 protein levels |
3e-93 |
rs7251987 |
1 |
GCST90471073 |
no MR -> candidate analysis |
| Prostate cancer |
5e-79 |
rs12976534 |
21 |
GCST90274713 |
MR: beta=0.0666, p=0.029 (cis) |
| PYDC1 protein levels |
8e-61 |
rs761061860 |
1 |
GCST90470397 |
no MR -> candidate analysis |
| Circulating PRSS8 levels |
9e-46 |
rs57822461 |
2 |
GCST90859807 |
no MR -> candidate analysis |
| Cancer of prostate (PheCode 185) |
3e-43 |
rs12610267 |
2 |
GCST90475591 |
no MR -> candidate analysis |
| Circulating CDSN levels |
2e-36 |
rs58711382 |
1 |
GCST90860191 |
no MR -> candidate analysis |
| Kunitz-type protease inhibitor 2 levels |
4e-34 |
rs11548457 |
5 |
GCST90161509 |
no MR -> candidate analysis |
| Hematological traits (multi-trait analysis) |
4e-32 |
rs4802324 |
1 |
GCST90838669 |
no MR -> candidate analysis |
| PRSS8 protein levels |
2e-31 |
rs58560372 |
1 |
GCST90470345 |
no MR -> candidate analysis |
| …and 38 more traits (see JSON) |
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4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 169 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 |
| congenital sodium diarrhea |
0.871 |
— |
established (curated) |
no MR -> candidate analysis |
| syndromic congenital sodium diarrhea |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| prostate carcinoma |
0.725 |
— |
common-variant locus |
no MR -> candidate analysis |
| abdominal abscess |
0.456 |
— |
common-variant locus |
no MR -> candidate analysis |
| digestive system disorder |
0.456 |
— |
common-variant locus |
no MR -> candidate analysis |
| hereditary disease |
0.313 |
— |
established (curated) |
no MR -> candidate analysis |
| prostate cancer |
0.144 |
— |
common-variant locus |
MR: beta=0.0666, p=0.029 (cis) |
| diverticular disease |
0.135 |
— |
common-variant locus |
MR: beta=0.0506, p=0.00659 (cis) |
| intestinal disorder |
0.116 |
— |
common-variant locus |
no MR -> candidate analysis |
| cancer |
0.091 |
— |
common-variant locus |
MR: beta=0.0936, p=0.00489 (cis) |
Of the 10 rows above, 7 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 |
0 known modulators (Kunitz-type protease inhibitor 2) |
| gnomAD constraint |
pLI=0.00044, LOEUF=0.886 — LoF-tolerant |
| GWAS Catalog |
95 unique SNPs / 189 rows |
| ClinVar |
226 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 169 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘SPINT2’ and resolved to ‘Kunitz-type protease inhibitor 2’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 226 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 50 traits by best p-value, aggregated from 91 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/O43291 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000167642/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL6066288/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/SPINT2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SPINT2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SPINT2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SPINT2 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:12:52 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none