CausalSentinel

Protein Dossier — GUCA1A (Guanylyl cyclase-activating protein 1)

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
Systolic blood pressure automated reading 0.0206 0.00652 0.00161 Wald ratio 1 trans NA
Eye problems or disorders: Glaucoma 0.145 0.046 0.00168 Wald ratio 1 trans NA
Fractured bone site(s): Wrist 0.112 0.0407 0.00605 Wald ratio 1 trans NA
Cough on most days 0.0811 0.0302 0.00717 Wald ratio 1 trans NA
Diagnoses - main ICD10: R11 Nausea and vomiting -0.389 0.154 0.0116 Wald ratio 1 trans NA
Eye problems or disorders: Diabetes related eye disease -0.247 0.106 0.0193 Wald ratio 1 trans NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0764 0.0328 0.0198 Wald ratio 1 trans NA
Small vessel disease -0.222 0.0965 0.0215 Wald ratio 1 trans NA
Diagnoses - main ICD10: G47 Sleep disorders 0.151 0.0719 0.0362 Wald ratio 1 trans NA
Forearm bone mineral density 0.0858 0.0413 0.0379 Wald ratio 1 trans NA
Fractured bone site(s): Ankle -0.128 0.0621 0.0395 Wald ratio 1 trans NA
Diagnoses - main ICD10: M54 Dorsalgia 0.0923 0.0452 0.0411 Wald ratio 1 trans NA
…and 80 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

3 association rows across 2 traits (2 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
Femur bone mineral density x serum urate levels interaction 2e-13 rs11752636 2 GCST012490 no MR -> candidate analysis
Spatial processing 5e-6 rs13203733 1 GCST009306 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 436 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
cone dystrophy 3 0.958 established (curated) no MR -> candidate analysis
Cone rod dystrophy 0.853 established (curated) no MR -> candidate analysis
Progressive cone dystrophy 0.847 established (curated) no MR -> candidate analysis
cone-rod dystrophy 0.72 established (curated) no MR -> candidate analysis
cone-rod dystrophy 14 0.745 established (curated) no MR -> candidate analysis
Retinal dystrophy 0.888 established (curated) no MR -> candidate analysis
Macular dystrophy 0.654 established (curated) no MR -> candidate analysis
Rod-cone dystrophy 0.486 established (curated) no MR -> candidate analysis
central areolar choroidal dystrophy 0.608 established (curated) no MR -> candidate analysis
retinitis pigmentosa 0.544 established (curated) no MR -> candidate analysis
Usher syndrome 0.547 established (curated) no MR -> candidate analysis
retinal disorder 0.559 established (curated) no MR -> candidate analysis
isolated macular dystrophy 0.559 established (curated) no MR -> candidate analysis
hereditary disease 0.307 established (curated) no MR -> candidate analysis

Of the 14 rows above, 14 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=0.00016, LOEUF=1.18 — LoF-tolerant
GWAS Catalog 20 unique SNPs / 40 rows
ClinVar 297 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance