CausalSentinel

Protein Dossier — CPA2 (Carboxypeptidase A2)

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
Alcohol intake frequency -0.0295 0.013 0.0238 Wald ratio 1 trans NA
Primary sclerosing cholangitis -0.28 0.127 0.0275 Wald ratio 1 trans NA
Diagnoses - main ICD10: R11 Nausea and vomiting -0.646 0.297 0.0297 Wald ratio 1 trans NA
Sodium in urine -0.0188 0.00868 0.0306 Wald ratio 1 trans NA
Non-cancer illness code self-reported: sleep apnoea 0.263 0.125 0.0349 Wald ratio 1 trans NA
Systolic blood pressure automated reading 0.0182 0.00903 0.0436 Wald ratio 1 trans NA
Diagnoses - main ICD10: G47 Sleep disorders 0.19 0.0962 0.0485 Wald ratio 1 trans NA
Cancer code self-reported: prostate cancer -0.263 0.137 0.0557 Wald ratio 1 trans NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation -0.135 0.0707 0.056 Wald ratio 1 trans NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate -0.281 0.147 0.0562 Wald ratio 1 trans NA
Squamous cell lung cancer -0.203 0.112 0.0701 Wald ratio 1 trans NA
Eye problems or disorders: Glaucoma 0.118 0.0657 0.0723 Wald ratio 1 trans NA
…and 65 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

20 association rows across 14 traits (18 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
Circulating CPA2 levels 3e-832 rs6952090 4 GCST90859671 no MR -> candidate analysis
Carboxypeptidase A4 levels (CPA4.9267.2.3) 9e-311 rs4731674 1 GCST90240596 no MR -> candidate analysis
Cerebrospinal fluid protein CPA2 levels 1e-157 rs6952090 1 GCST90944210 no MR -> candidate analysis
Carboxypeptidase A4 levels 1e-131 rs73146784 1 GCST90246874 no MR -> candidate analysis
CPA2 protein levels 2e-103 rs751189658 4 GCST90468837 no MR -> candidate analysis
Cerebrospinal fluid protein CPA4 levels 5e-59 rs73146784 1 GCST90944211 no MR -> candidate analysis
Carboxypeptidase A2 levels 3e-37 rs2171493 1 GCST90059933 no MR -> candidate analysis
HS6ST1 protein levels 1e-22 rs10257530 1 GCST90469479 no MR -> candidate analysis
Circulating HS6ST1 levels 4e-22 rs6952090 1 GCST90860515 no MR -> candidate analysis
Neurological blood protein biomarker levels 9e-15 rs112255027 1 GCST008478 no MR -> candidate analysis
Asparaginase-induced acute pancreatitis in acute lymphoblast 2e-8 rs199695765 1 GCST003501 no MR -> candidate analysis
Body shape phenotype PC3 4e-8 rs62489501 1 GCST90832991 no MR -> candidate analysis
…and 2 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 435 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
exostosis 0.36 common-variant locus no MR -> candidate analysis
drug allergy 0.337 common-variant locus no MR -> candidate analysis

Of the 2 rows above, 2 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 A2)
gnomAD constraint pLI=3.9e-18, LOEUF=1.26 — LoF-tolerant
GWAS Catalog 80 unique SNPs / 160 rows
ClinVar 91 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance