CausalSentinel

Protein Dossier — SPINK2 (Serine protease inhibitor Kazal-type 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
Squamous cell lung cancer -0.31 0.0649 1.79e-06 Inverse variance weighted 2 trans 2.96e-07
Squamous cell lung cancer -0.31 0.0649 1.79e-06 Inverse variance weighted 2 cis 0.834
Diagnoses - main ICD10: I83 Varicose veins of lower extremities 0.129 0.0526 0.0141 Wald ratio 1 cis NA
Non-cancer illness code self-reported: polio or poliomyelitis 0.504 0.208 0.0152 Wald ratio 1 cis NA
Cough on most days -0.11 0.0483 0.0224 Wald ratio 1 cis NA
Primary sclerosing cholangitis -0.235 0.121 0.052 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia -0.113 0.0631 0.0722 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.149 0.0863 0.0842 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia -0.135 0.0789 0.0862 Wald ratio 1 cis NA
Neuroticism -0.0352 0.0205 0.0865 Wald ratio 1 trans NA
Depressive symptoms -0.044 0.0264 0.0956 Wald ratio 1 trans NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.0716 0.0444 0.107 Wald ratio 1 cis NA
…and 70 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

147 association rows across 95 traits (135 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 inhibitor Kazal-type 2 levels 2e-111 rs781538 2 GCST90422125 no MR -> candidate analysis
Cerebrospinal fluid protein SPINK2 levels 9e-110 rs146649464 1 GCST90944595 no MR -> candidate analysis
Height 1e-109 rs66790703 9 GCST90662911 no MR -> candidate analysis
Platelet count 2e-77 rs7665147 9 GCST90662907 no MR -> candidate analysis
Cerebellar grey matter morphology (MOSTest) 6e-60 rs3806746 1 GCST90728589 no MR -> candidate analysis
Serum levels of protein SPINK2 1e-57 rs34393987 2 GCST90087423 no MR -> candidate analysis
CBLN4 protein levels 9e-53 rs571492629 1 GCST90468554 no MR -> candidate analysis
SPINK2 protein levels 5e-50 rs11133463 4 GCST90470722 no MR -> candidate analysis
Platelet count (UKB data field 30080) 2e-42 rs58408429 1 GCST90468095 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 2e-38 rs55762216 1 GCST90468087 no MR -> candidate analysis
Serine protease inhibitor Kazal-type 2 levels (SPINK2.13405. 2e-33 rs11941335 1 GCST90242763 no MR -> candidate analysis
White blood cell count 3e-31 rs58408429 6 GCST90002378 no MR -> candidate analysis
…and 83 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 161 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
spermatogenic failure 29 0.596 established (curated) no MR -> candidate analysis
male infertility with azoospermia or oligozoospermia due to single gene mutation 0.608 established (curated) no MR -> candidate analysis
migraine disorder 0.417 common-variant locus no MR -> candidate analysis
Pain 0.319 common-variant locus MR: beta=-0.0716, p=0.107 (cis)
nervous system benign neoplasm 0.209 common-variant locus no MR -> candidate analysis
risk-taking behaviour 0.116 common-variant locus no MR -> candidate analysis

Of the 6 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=0.022, LOEUF=1.07 — LoF-tolerant
GWAS Catalog 118 unique SNPs / 246 rows
ClinVar 47 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance