CausalSentinel

Protein Dossier — GPHA2 (Glycoprotein hormone alpha-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
Eye problems or disorders: Glaucoma 0.124 0.0392 0.00161 Wald ratio 1 trans NA
Systolic blood pressure automated reading 0.017 0.00545 0.00181 Wald ratio 1 trans NA
Fractured bone site(s): Wrist 0.0972 0.0345 0.00488 Wald ratio 1 trans NA
Mean cell haemoglobin concentration 0.0224 0.00798 0.00494 Wald ratio 1 trans NA
Diagnoses - main ICD10: R11 Nausea and vomiting -0.325 0.119 0.00651 Wald ratio 1 trans NA
Cough on most days 0.0683 0.0255 0.00743 Wald ratio 1 trans NA
Eye problems or disorders: Diabetes related eye disease -0.2 0.0838 0.0167 Wald ratio 1 trans NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0617 0.0274 0.0243 Wald ratio 1 trans NA
Small vessel disease -0.176 0.0792 0.026 Wald ratio 1 trans NA
Percent emphysema -0.0902 0.0423 0.033 Wald ratio 1 trans NA
Diagnoses - main ICD10: G47 Sleep disorders 0.13 0.0613 0.0345 Wald ratio 1 trans NA
Diagnoses - main ICD10: M54 Dorsalgia 0.0794 0.0382 0.0378 Wald ratio 1 trans NA
…and 98 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

2 association rows across 2 traits (1 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
Uric acid levels 2e-63 rs1174410819 1 GCST90239629 no MR -> candidate analysis
Squamous cell lung carcinoma 9e-6 rs148033979 1 GCST90652535 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 83 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
adolescent idiopathic scoliosis 0.053 common-variant locus no MR -> candidate analysis

Of the 1 rows above, 1 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=0.00037, LOEUF=1.27 — LoF-tolerant
GWAS Catalog 45 unique SNPs / 88 rows
ClinVar 36 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance