CausalSentinel

Protein Dossier — CPA4 (Carboxypeptidase A4)

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
Diastolic blood pressure automated reading 0.00842 0.00218 1.09e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0112 0.00358 0.00174 Wald ratio 1 cis NA
Body mass index (BMI) 0.00654 0.00212 0.00208 Wald ratio 1 cis NA
Systolic blood pressure automated reading 0.00639 0.00217 0.00329 Wald ratio 1 cis NA
Neo-openness to experience 0.181 0.0617 0.00335 Wald ratio 1 cis NA
Schizophrenia 0.0261 0.00935 0.00529 Wald ratio 1 cis NA
Cigarettes smoked per day 0.202 0.0733 0.00572 Wald ratio 1 cis NA
Platelet count 0.934 0.35 0.00761 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia 0.0344 0.0135 0.0106 Wald ratio 1 cis NA
Urate -0.012 0.0048 0.0124 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia 0.0304 0.0126 0.0159 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine 0.00482 0.00203 0.0178 Wald ratio 1 cis NA
…and 106 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

29 association rows across 18 traits (25 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
Carboxypeptidase A4 levels 2e-3800 rs34587586 2 GCST90246874 no MR -> candidate analysis
Carboxypeptidase A4 levels (CPA4.9267.2.3) 4e-1248 rs34587586 2 GCST90240596 no MR -> candidate analysis
Blood protein levels 4e-332 rs729167 1 GCST006585 no MR -> candidate analysis
CPA4 protein levels 2e-296 rs145012020 9 GCST90468838 no MR -> candidate analysis
Carboxypeptidase A4 level in Chronic kidney disease with hyp 2e-161 rs34587586 1 GCST90239281 no MR -> candidate analysis
Cerebrospinal fluid protein CPA4 levels 5e-59 rs73146784 1 GCST90944211 no MR -> candidate analysis
Sclerostin protein levels (SomaScan ID:9267-2) 3e-44 rs34587586 1 GCST90444071 no MR -> candidate analysis
CPA2 protein levels 2e-37 rs55811503 2 GCST90468837 no MR -> candidate analysis
Rheumatoid arthritis 6e-12 rs2306848 1 GCST007843 no MR -> candidate analysis
Height 6e-12 rs6467297 1 GCST90245848 no MR -> candidate analysis
Hip index 3e-11 rs7787960 1 GCST90020026 no MR -> candidate analysis
A body shape index 2e-9 rs7797371 1 GCST90020024 no MR -> candidate analysis
…and 6 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 98 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
rheumatoid arthritis 0.264 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.051 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.042 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 0 known modulators (Carboxypeptidase A4)
gnomAD constraint pLI=1.7e-15, LOEUF=1.14 — LoF-tolerant
GWAS Catalog 91 unique SNPs / 182 rows
ClinVar 103 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance