CausalSentinel

Protein Dossier — BPIFB1 (BPI fold-containing family B member 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
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0458 0.0179 0.0103 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.0426 0.0177 0.0159 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0353 0.0149 0.0178 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux -0.0664 0.0289 0.0216 Wald ratio 1 cis NA
Hirschsprung’s disease -0.871 0.387 0.0245 Wald ratio 1 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.107 0.0478 0.0246 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.0457 0.0206 0.0269 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema -0.056 0.0264 0.0338 Wald ratio 1 cis NA
Mean cell haemoglobin concentration 0.0405 0.0195 0.0373 Wald ratio 1 cis NA
Systolic blood pressure automated reading 0.0114 0.00574 0.0465 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine 0.0598 0.0306 0.0504 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities 0.0694 0.0366 0.0577 Wald ratio 1 cis NA
…and 68 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

15 association rows across 9 traits (13 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
BPIFB1 protein levels 5e-281 rs1884886 5 GCST90468462 no MR -> candidate analysis
Serum levels of protein BPIFB1 2e-31 rs117258330 2 GCST90086636 no MR -> candidate analysis
LPO protein levels 7e-27 rs61739245 1 GCST90469789 no MR -> candidate analysis
Height (baseline) 2e-16 rs117461583 2 GCST90565843 no MR -> candidate analysis
PROC protein levels 2e-15 rs200193317 1 GCST90470335 no MR -> candidate analysis
BPI fold-containing family B member 1 levels (BPIFB1.11246.3 7e-15 rs117258330 1 GCST90240464 no MR -> candidate analysis
Height (standard GWA) 2e-12 rs75744141 1 GCST90267284 no MR -> candidate analysis
Breast cancer 8e-7 rs4911315 1 GCST90011804 MR: beta=-0.0458, p=0.0103 (cis)
Height (weighted GWA) 9e-7 rs75744141 1 GCST90267285 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 482 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
poisoning 0.459 common-variant locus no MR -> candidate analysis
squamous cell carcinoma 0.421 common-variant locus no MR -> candidate analysis
liver disorder 0.389 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 3 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=3.5e-07, LOEUF=0.821 — LoF-tolerant
GWAS Catalog 51 unique SNPs / 98 rows
ClinVar 90 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance