CausalSentinel

Protein Dossier — AP1G2 (AP-1 complex subunit gamma-like 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: C50 Malignant neoplasm of breast 0.226 0.0793 0.00434 Wald ratio 1 cis NA
Non-cancer illness code self-reported: ankylosing spondylitis 0.418 0.162 0.0102 Wald ratio 1 cis NA
Height -0.041 0.0164 0.0124 Wald ratio 1 cis NA
Depressive symptoms 0.0522 0.0224 0.0196 Wald ratio 1 cis NA
Endometrioid ovarian cancer 0.483 0.214 0.0242 Wald ratio 1 cis NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone -0.595 0.285 0.0367 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia 0.149 0.0719 0.038 Wald ratio 1 cis NA
Paget’s disease -0.634 0.309 0.0399 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine 0.127 0.0646 0.0501 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated -0.0312 0.0164 0.0564 Wald ratio 1 cis NA
Birth length -0.101 0.0534 0.0572 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.0242 0.0129 0.0607 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

7 association rows across 6 traits (6 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
AP1G2 protein levels 6e-38 rs77436356 2 GCST90468323 no MR -> candidate analysis
AP-1 complex subunit gamma-like 2 levels 1e-34 rs12897422 1 GCST90246528 no MR -> candidate analysis
THTPA protein levels 1e-15 rs12897422 1 GCST90470860 no MR -> candidate analysis
Blood protein levels 1e-14 rs12897422 1 GCST006585 no MR -> candidate analysis
Eosinophil count 3e-8 rs77436356 1 GCST007065 no MR -> candidate analysis
Sudden cardiac arrest 6e-8 rs2281680 1 GCST001099 no MR -> candidate analysis

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

Top diseases by Open Targets association (of 62 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
Tracheoesophageal fistula 0.426 established (curated) no MR -> candidate analysis
esophageal atresia/tracheoesophageal fistula 0.426 established (curated) no MR -> candidate analysis
Global developmental delay 0.195 established (curated) no MR -> candidate analysis
Genu valgum 0.072 common-variant locus no MR -> candidate analysis
Genu varum 0.072 common-variant locus no MR -> candidate analysis

Of the 5 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=7.1e-26, LOEUF=1.06 — LoF-tolerant
GWAS Catalog 17 unique SNPs / 34 rows
ClinVar 179 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance