CausalSentinel

Protein Dossier — GKN2 (Gastrokine-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
Lung adenocarcinoma 0.212 0.0633 8.28e-04 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.012 0.00468 0.0102 Wald ratio 1 cis NA
Age at menopause 0.159 0.0637 0.0124 Wald ratio 1 cis NA
Fracture resulting from simple fall -0.0371 0.0155 0.017 Wald ratio 1 cis NA
Cough on most days -0.0608 0.031 0.0498 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.118 0.0606 0.0512 Wald ratio 1 cis NA
Putamen volume -32.5 16.7 0.0519 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pneumothorax 0.383 0.2 0.0552 Wald ratio 1 cis NA
Platelet count -4.86 2.55 0.0567 Wald ratio 1 cis NA
Height -0.0234 0.0127 0.0668 Wald ratio 1 cis NA
Diagnoses - main ICD10: G47 Sleep disorders 0.118 0.0664 0.0753 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma 0.0768 0.0439 0.0804 Wald ratio 1 cis NA
…and 82 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

18 association rows across 11 traits (15 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
TFF1/TFF2 protein level ratio 2e-317 rs62133345 1 GCST90315914 no MR -> candidate analysis
Gastrokine-2 levels 9e-288 rs62133344 2 GCST90247690 no MR -> candidate analysis
TFF1 protein levels 2e-204 rs62133344 2 GCST90470835 no MR -> candidate analysis
Trefoil factor 1 levels 2e-104 rs62133344 4 GCST90249813 no MR -> candidate analysis
Serum levels of protein GKN2 6e-99 rs62133344 1 GCST90089413 no MR -> candidate analysis
Blood protein levels 3e-34 rs13008230 2 GCST006585 no MR -> candidate analysis
Serum levels of protein TFF1 2e-27 rs62133344 2 GCST90090541 no MR -> candidate analysis
BMP10 protein levels 3e-17 rs76746873 1 GCST90468452 no MR -> candidate analysis
Benign neoplasm of unspecified sites (PheCode 229) 6e-8 rs75502905 1 GCST90651747 no MR -> candidate analysis
Adiponectin levels 1e-7 rs6705747 1 GCST012168 no MR -> candidate analysis
Lung cancer 5e-6 rs4254535 1 GCST000459 MR: beta=0.0372, p=0.437 (cis)

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 69 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
Abnormality of the skeletal system 0.472 common-variant locus no MR -> candidate analysis
aortic valve stenosis 0.07 common-variant locus no MR -> candidate analysis

Of the 2 rows above, 2 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=3.3e-05, LOEUF=1.13 — LoF-tolerant
GWAS Catalog 32 unique SNPs / 64 rows
ClinVar 38 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance