CausalSentinel

Protein Dossier — C4BPA (C4b-binding protein alpha chain)

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
Rheumatoid arthritis 0.158 0.0498 0.00155 Wald ratio 1 cis NA
Non-cancer illness code self-reported: muscle or soft tissue injuries 0.249 0.0806 0.00205 Wald ratio 1 cis NA
Forearm bone mineral density -0.154 0.0537 0.00418 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia 0.142 0.0496 0.00427 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertrophic cardiomyopathy (hcm or hocm) 0.821 0.297 0.00568 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma -0.241 0.0932 0.00973 Wald ratio 1 cis NA
Platelet count 3.48 1.42 0.0141 Wald ratio 1 cis NA
Lumbar spine bone mineral density -0.073 0.0301 0.0152 Wald ratio 1 cis NA
Diagnoses - main ICD10: R55 Syncope and collapse 0.183 0.0773 0.0178 Wald ratio 1 cis NA
Myocardial infarction 0.0804 0.0341 0.0183 Wald ratio 1 cis NA
Anorexia nervosa 0.255 0.111 0.0212 Wald ratio 1 cis NA
Low grade serous ovarian cancer -0.414 0.18 0.0212 Wald ratio 1 cis NA
…and 101 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

63 association rows across 45 traits (60 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
C4b-binding protein alpha chain levels 1e-151 rs34101855 1 GCST90246784 no MR -> candidate analysis
CD55 protein levels 1e-105 rs72742944 1 GCST90468637 no MR -> candidate analysis
Serum levels of protein S100A5 2e-83 rs4844573 2 GCST90087838 no MR -> candidate analysis
Killer cell lectin-like receptor subfamily G member 2 levels 2e-59 rs2808467 1 GCST90248210 no MR -> candidate analysis
Protein S100-A5 levels (S100A5.14222.68.3) 1e-58 rs17020993 2 GCST90242509 no MR -> candidate analysis
Serum levels of protein C4BPA 3e-50 rs11120218 1 GCST90090695 no MR -> candidate analysis
Blood protein levels 9e-45 rs11120218 4 GCST006585 no MR -> candidate analysis
Platelet distribution width (UKB data field 30110) 8e-39 rs11120218 1 GCST90468097 no MR -> candidate analysis
CR1 protein levels 9e-36 rs12064010 3 GCST90468851 no MR -> candidate analysis
C1q-related factor levels 2e-34 rs4266889 1 GCST90246765 no MR -> candidate analysis
Mean platelet volume 1e-31 rs12074166 4 GCST90002346 MR: beta=0.00606, p=0.104 (cis)
C4BPA protein levels 8e-30 rs11120218 2 GCST90453101 no MR -> candidate analysis
…and 33 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 394 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
venous thromboembolism 0.637 common-variant locus no MR -> candidate analysis
Thromboembolism 0.503 common-variant locus no MR -> candidate analysis
deep vein thrombosis 0.393 common-variant locus no MR -> candidate analysis
age-related macular degeneration 0.083 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 4 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=0.001, LOEUF=0.656 — LoF-tolerant
GWAS Catalog 80 unique SNPs / 165 rows
ClinVar 122 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance