CausalSentinel

Protein Dossier — CPZ (Carboxypeptidase Z)

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: J33 Nasal polyp 0.398 0.122 0.00112 Wald ratio 1 cis NA
Pulse rate 0.0569 0.0217 0.00879 Wald ratio 1 cis NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation 0.183 0.0718 0.0109 Wald ratio 1 cis NA
Age at menarche -0.0872 0.0343 0.011 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities 0.182 0.0721 0.0115 Wald ratio 1 cis NA
Non-cancer illness code self-reported: mania or bipolar disorder or manic depression 0.404 0.167 0.0152 Wald ratio 1 cis NA
Weight 0.025 0.0109 0.0214 Wald ratio 1 cis NA
Height 0.0375 0.0169 0.027 Wald ratio 1 cis NA
Alcohol intake frequency -0.0381 0.0182 0.0365 Wald ratio 1 cis NA
Non-cancer illness code self-reported: arthritis (nos) 0.236 0.114 0.0381 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0327 0.0159 0.0405 Wald ratio 1 cis NA
Large vessel disease 0.356 0.174 0.0412 Wald ratio 1 cis NA
…and 89 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

46 association rows across 26 traits (40 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
Height 1e-191 rs11723641 15 GCST90245848 MR: beta=0.0375, p=0.027 (cis)
height (mean, inv-normal transformed) 3e-123 rs3756173 2 GCST90475362 no MR -> candidate analysis
Height (maximum, inv-normal transformed) 1e-111 rs3756173 2 GCST90475359 no MR -> candidate analysis
height (minimum, inv-normal transformed) 9e-106 rs3756173 2 GCST90475365 no MR -> candidate analysis
Carboxypeptidase Z levels 2e-68 rs13121547 1 GCST90426728 no MR -> candidate analysis
SOD3 protein levels 2e-64 rs3796735 1 GCST90470706 no MR -> candidate analysis
Standing height (UKB data field 50) 1e-45 rs3756173 1 GCST90468178 no MR -> candidate analysis
Height (baseline) 1e-40 rs4621412 2 GCST90565843 no MR -> candidate analysis
Cerebrospinal fluid protein CPZ levels 6e-40 rs11723641 1 GCST90942032 no MR -> candidate analysis
Body shape phenotype PC2 9e-32 rs4621412 1 GCST90832990 no MR -> candidate analysis
What is your height? (cm, inv-normal transformed) 1e-18 rs2302580 1 GCST90479637 no MR -> candidate analysis
Physical function (baseline) 2e-15 rs13127468 1 GCST90565837 no MR -> candidate analysis
…and 14 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 237 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
Abnormality of the skeletal system 0.723 common-variant locus no MR -> candidate analysis
Short stature 0.532 established (curated) no MR -> candidate analysis
neuroblastoma 0.509 common-variant locus no MR -> candidate analysis
amputation 0.185 common-variant locus no MR -> candidate analysis
drug allergy 0.182 common-variant locus no MR -> candidate analysis
systemic lupus erythematosus 0.178 common-variant locus no MR -> candidate analysis
liver disorder 0.17 common-variant locus no MR -> candidate analysis
lymphatic system disorder 0.152 common-variant locus no MR -> candidate analysis
vein disorder 0.152 common-variant locus no MR -> candidate analysis
placental abruption 0.135 common-variant locus no MR -> candidate analysis
osteoporosis 0.11 common-variant locus no MR -> candidate analysis
poisoning 0.11 common-variant locus no MR -> candidate analysis
response to xenobiotic stimulus 0.11 common-variant locus no MR -> candidate analysis
kidney disorder 0.108 common-variant locus no MR -> candidate analysis
gout 0.1 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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=1.3e-49, LOEUF=1.96 — LoF-tolerant
GWAS Catalog 54 unique SNPs / 108 rows
ClinVar 404 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance