MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
| Outcome | beta | se | p | method | nSNP | cis/trans | coloc |
|---|---|---|---|---|---|---|---|
| Total cholesterol | 0.103 | 0.0342 | 0.00253 | Wald ratio | 1 | cis | NA |
| LDL cholesterol | 0.1 | 0.0349 | 0.00413 | Wald ratio | 1 | cis | NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) | -0.12 | 0.0428 | 0.00511 | Wald ratio | 1 | cis | NA |
| High grade serous ovarian cancer | -0.291 | 0.107 | 0.00675 | Wald ratio | 1 | cis | NA |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) | -0.192 | 0.0776 | 0.0133 | Wald ratio | 1 | cis | NA |
| Type 2 diabetes | 0.194 | 0.0811 | 0.0165 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: K20 Oesophagitis | 0.291 | 0.126 | 0.0204 | Wald ratio | 1 | cis | NA |
| Fracture resulting from simple fall | 0.0896 | 0.0391 | 0.0219 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: B37 Candidiasis | 0.858 | 0.391 | 0.0283 | Wald ratio | 1 | cis | NA |
| Neo-agreeableness | -0.886 | 0.412 | 0.0318 | Wald ratio | 1 | cis | NA |
| 2hr glucose | 0.263 | 0.125 | 0.0353 | Wald ratio | 1 | cis | NA |
| Knee osteoarthritis | 0.383 | 0.19 | 0.0439 | Wald ratio | 1 | cis | NA |
| …and 84 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
34 association rows across 21 traits (28 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 |
|---|---|---|---|---|---|
| NECTIN4/SPINK5 protein level ratio | 8e-977 | rs3777134 | 1 | GCST90315534 | no MR -> candidate analysis |
| Circulating SPINK5 levels | 1e-922 | rs6883868 | 7 | GCST90860662 | no MR -> candidate analysis |
| SPINK5/SPINT1 protein level ratio | 2e-899 | rs3777134 | 1 | GCST90315877 | no MR -> candidate analysis |
| DSG3/SPINK5 protein level ratio | 6e-890 | rs3777134 | 1 | GCST90314561 | no MR -> candidate analysis |
| SPINK6 protein levels | 2e-31 | rs12657423 | 2 | GCST90470725 | no MR -> candidate analysis |
| Erythematosquamous dermatosis (PheCode 690) | 1e-19 | rs7445392 | 1 | GCST90480446 | no MR -> candidate analysis |
| Seborrheic dermatitis (PheCode 690.1) | 4e-19 | rs7700488 | 1 | GCST90480445 | no MR -> candidate analysis |
| GLIPR1 protein levels | 2e-18 | rs140204639 | 2 | GCST90469357 | no MR -> candidate analysis |
| SPINK5 protein levels | 4e-17 | rs561267584 | 5 | GCST90470724 | no MR -> candidate analysis |
| Non-alcoholic chronic pancreatitis | 7e-17 | rs112861203 | 1 | GCST90104595 | no MR -> candidate analysis |
| SPINK1 protein levels | 2e-16 | rs115812194 | 2 | GCST90470721 | no MR -> candidate analysis |
| Q9NQ38-3 protein level (protein group normalized intensity) | 5e-14 | rs3764930 | 1 | GCST90570894 | no MR -> candidate analysis |
| …and 9 more traits (see JSON) |
Top diseases by Open Targets association (of 896 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 |
|---|---|---|---|---|
| Netherton syndrome | 0.874 | — | established (curated) | no MR -> candidate analysis |
| ichthyosis linearis circumflexa | 0.942 | — | established (curated) | no MR -> candidate analysis |
| erythematosquamous dermatosis | 0.615 | — | common-variant locus | no MR -> candidate analysis |
| seborrheic dermatitis | 0.61 | — | common-variant locus | no MR -> candidate analysis |
| exfoliative dermatitis | 0.547 | — | established (curated) | no MR -> candidate analysis |
| Increased circulating IgE concentration | 0.547 | — | established (curated) | no MR -> candidate analysis |
| hereditary disease | 0.318 | — | established (curated) | no MR -> candidate analysis |
| ovarian dysfunction | 0.286 | — | 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.
| Layer | Result |
|---|---|
| ChEMBL druggability | not available — no ChEMBL target (undrugged) |
| gnomAD constraint | pLI=9.6e-35, LOEUF=0.955 — LoF-tolerant |
| GWAS Catalog | 50 unique SNPs / 100 rows |
| ClinVar | 1221 records; 7 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 896 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — No ChEMBL target for ‘SPINK5’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 1221 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 21 traits by best p-value, aggregated from 34 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.uniprot: https://www.uniprot.org/uniprotkb/Q9NQ38 — 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/ENSG00000133710/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/SPINK5 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SPINK5 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SPINK5%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SPINK5 — GWAS Catalog search API (live; release not exposed)