CausalSentinel

Protein Dossier — EPHB3 (Ephrin type-B receptor 3)

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: R04 Haemorrhage from respiratory passages 0.268 0.102 0.00843 Wald ratio 1 trans NA
Non-cancer illness code self-reported: enlarged prostate 0.169 0.0687 0.0139 Wald ratio 1 trans NA
Eye problems or disorders: Diabetes related eye disease 0.23 0.0976 0.0184 Wald ratio 1 trans NA
Red blood cell count 0.0228 0.0104 0.0289 Wald ratio 1 trans NA
Non-cancer illness code self-reported: migraine -0.135 0.0629 0.0318 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema -0.099 0.0466 0.0335 Wald ratio 1 trans NA
High grade serous ovarian cancer -0.138 0.0657 0.0351 Wald ratio 1 trans NA
Squamous cell lung cancer 0.216 0.105 0.0389 Wald ratio 1 trans NA
Non-cancer illness code self-reported: retinal detachment 0.262 0.129 0.0428 Wald ratio 1 trans NA
Neo-neuroticism 0.758 0.384 0.0484 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoporosis 0.131 0.067 0.0499 Wald ratio 1 trans NA
Non-cancer illness code self-reported: psoriasis 0.137 0.0782 0.0793 Wald ratio 1 trans 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

28 association rows across 27 traits (14 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
Facial appearance 1e-34 rs12633616 1 GCST90128425 no MR -> candidate analysis
Facial morphology (segment 5) 3e-26 rs58022575 1 GCST90007185 no MR -> candidate analysis
Nose size 2e-15 rs13097965 1 GCST003999 no MR -> candidate analysis
Sib-shared facial trait 117; Facial segment 2; 3D morphology 3e-13 rs142433965 1 GCST90015630 no MR -> candidate analysis
Height 7e-13 rs4234607 1 GCST90245848 MR: beta=0.0216, p=0.0801 (trans)
Non-proliferative glomerulonephritis (PheCode 580.12) 8e-13 rs181546322 1 GCST90480365 no MR -> candidate analysis
Pierre Robin Sequence endophenotypic score 2e-11 rs4072388 1 GCST90245763 no MR -> candidate analysis
Facial morphology (segment 6) 5e-11 rs56081252 1 GCST90007249 no MR -> candidate analysis
Facial morphology traits (63 three-dimensional facial segmen 8e-10 rs58022575 1 GCST007989 no MR -> candidate analysis
Heel bone mineral density 3e-8 rs9865980 1 GCST007066 MR: beta=-0.00928, p=0.448 (trans)
Lung function (FVC) 4e-8 rs4074283 1 GCST007081 no MR -> candidate analysis
Body mass index 4e-8 rs7373175 1 GCST90255622 MR: beta=0.0127, p=0.178 (trans)
…and 15 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 217 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
alcohol drinking 0.583 common-variant locus no MR -> candidate analysis
corneal neovascularization 0.389 common-variant locus no MR -> candidate analysis
Abnormality of limbs 0.293 common-variant locus no MR -> candidate analysis
liver disorder 0.293 common-variant locus no MR -> candidate analysis
nerve plexus disorder 0.262 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.251 common-variant locus no MR -> candidate analysis
adolescent idiopathic scoliosis 0.251 common-variant locus no MR -> candidate analysis
age-related macular degeneration 0.2 common-variant locus no MR -> candidate analysis
Hematemesis 0.2 common-variant locus no MR -> candidate analysis

Of the 9 rows above, 9 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 0 known modulators (Ephrin type-B receptor 3)
gnomAD constraint pLI=1, LOEUF=0.44 — LoF-INTOLERANT
GWAS Catalog 45 unique SNPs / 90 rows
ClinVar 171 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance