CausalSentinel

Protein Dossier — GABBR2 (Gamma-aminobutyric acid type B receptor subunit 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
Ovarian cancer -0.221 0.0868 0.0109 Wald ratio 1 trans NA
High grade serous ovarian cancer -0.193 0.103 0.0616 Wald ratio 1 trans NA
Percent emphysema -0.219 0.123 0.0749 Wald ratio 1 trans NA
Platelet count 6.4 3.73 0.0865 Wald ratio 1 trans NA
Invasive mucinous ovarian cancer -0.438 0.261 0.0932 Wald ratio 1 trans NA
Birth weight 0.037 0.0231 0.11 Wald ratio 1 trans NA
Mean platelet volume -0.0168 0.0109 0.124 Wald ratio 1 trans NA
Mean cell volume 0.527 0.354 0.136 Wald ratio 1 trans NA
Age at menarche 0.0925 0.0642 0.15 Wald ratio 1 trans NA
Amyotrophic lateral sclerosis 0.153 0.108 0.154 Wald ratio 1 trans NA
Forearm bone mineral density -0.153 0.125 0.223 Wald ratio 1 trans NA
Low grade serous ovarian cancer -0.384 0.316 0.225 Wald ratio 1 trans NA
…and 17 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

56 association rows across 39 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
Height 1e-23 rs1571928 3 GCST90245848 MR: beta=0.0214, p=0.46 (trans)
Smoking initiation 6e-20 rs1435257 2 GCST90243985 no MR -> candidate analysis
Circulating ANGPTL1 levels 3e-17 rs62563783 1 GCST90860358 no MR -> candidate analysis
Bone mineral density mean 4e-17 rs117618609 1 GCST90321120 no MR -> candidate analysis
Body mass index 2e-12 rs186809 3 GCST90662912 no MR -> candidate analysis
Duodenitis (PheCode 535.6) 3e-11 rs147399943 1 GCST90480302 no MR -> candidate analysis
Circulating ADGRG2 levels 4e-11 rs62563783 1 GCST90860360 no MR -> candidate analysis
Total PHF-tau (SNP x SNP interaction) 4e-11 rs2546892 x rs884886 2 GCST010340 no MR -> candidate analysis
Schizophrenia 1e-9 rs10985811 6 GCST90128471 no MR -> candidate analysis
Bone mineral density variability 2e-9 rs138018922 5 GCST90321121 no MR -> candidate analysis
Metabolic syndrome 2e-9 rs3889747 1 GCST90444487 no MR -> candidate analysis
Cervical dystonia (age at onset) 3e-9 rs147331823 1 GCST90027050 no MR -> candidate analysis
…and 27 more traits (see JSON)          

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

Top diseases by Open Targets association (of 270 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
developmental and epileptic encephalopathy, 59 0.845 established (curated) no MR -> candidate analysis
Epileptic encephalopathy 0.841 established (curated) no MR -> candidate analysis
neurodevelopmental disorder with poor language and loss of hand skills 0.827 established (curated) no MR -> candidate analysis
atypical Rett syndrome 0.73 established (curated) no MR -> candidate analysis
hereditary disease 0.742 established (curated) no MR -> candidate analysis
undetermined early-onset epileptic encephalopathy 0.608 established (curated) no MR -> candidate analysis
hypothyroidism 0.601 common-variant locus no MR -> candidate analysis
Rett syndrome 0.559 established (curated) no MR -> candidate analysis
autism spectrum disorder 0.195 established (curated) no MR -> candidate analysis
Intellectual disability 0.519 established (curated) no MR -> candidate analysis
Splenomegaly 0.479 common-variant locus no MR -> candidate analysis
self-injurious ideation 0.442 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.431 common-variant locus no MR -> candidate analysis

Of the 13 rows above, 13 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 1 known modulators (Gamma-aminobutyric acid type B receptor subunit 2)
gnomAD constraint pLI=1, LOEUF=0.309 — LoF-INTOLERANT
GWAS Catalog 64 unique SNPs / 128 rows
ClinVar 1221 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance