CausalSentinel

Protein Dossier — CPM (Carboxypeptidase M)

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
Heel bone mineral density (BMD) T-score automated 0.0665 0.0185 3.25e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate 0.251 0.0962 0.00901 Wald ratio 1 cis NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.843 0.332 0.0111 Wald ratio 1 cis NA
Systolic blood pressure automated reading -0.0366 0.0146 0.0124 Wald ratio 1 cis NA
Body mass index (BMI) -0.0339 0.0143 0.0179 Wald ratio 1 cis NA
Non-cancer illness code self-reported: mania or bipolar disorder or manic depression 0.429 0.191 0.0246 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.116 0.0525 0.0271 Wald ratio 1 cis NA
Non-cancer illness code self-reported: iron deficiency anaemia 0.316 0.147 0.0312 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia 0.154 0.0811 0.057 Wald ratio 1 cis NA
Non-cancer illness code self-reported: polio or poliomyelitis 0.626 0.332 0.059 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.0253 0.0146 0.0843 Wald ratio 1 cis NA
Diagnoses - main ICD10: R55 Syncope and collapse -0.439 0.254 0.0843 Wald ratio 1 cis NA
…and 50 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

64 association rows across 50 traits (38 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 M (analyte X9416.77) levels 3e-121 rs12372220 1 GCST90427805 no MR -> candidate analysis
Cerebrospinal fluid protein CPM levels 9e-119 rs12372220 1 GCST90944212 no MR -> candidate analysis
Carboxypeptidase M (analyte X7768.10) levels 7e-81 rs12372220 1 GCST90427056 no MR -> candidate analysis
CPM protein levels 3e-77 rs7978197 5 GCST90468843 no MR -> candidate analysis
Circulating CPM levels 4e-66 rs140860259 8 GCST90859711 no MR -> candidate analysis
CPM/LAMP2 protein level ratio 1e-48 rs11177417 1 GCST90314215 no MR -> candidate analysis
Height 5e-36 rs3741598 4 GCST90245848 no MR -> candidate analysis
Neutrophils and lymphocytes in blood (confirmatory factor an 2e-23 rs10784771 1 GCST90309369 no MR -> candidate analysis
Carboxypeptidase M levels 8e-20 rs7976135 1 GCST90246879 no MR -> candidate analysis
Cerebrospinal fluid N-acetylarginine levels 3e-13 rs12372220 1 GCST90317973 no MR -> candidate analysis
red blood cell count (RBC, mean, inv-norm transformed) 6e-12 rs73144210 1 GCST90480669 no MR -> candidate analysis
red blood cell count (RBC, maximum, inv-norm transformed) 8e-12 rs73144210 1 GCST90480668 no MR -> candidate analysis
…and 38 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 105 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
salivary gland disorder 0.508 common-variant locus no MR -> candidate analysis
diabetic ketoacidosis 0.461 common-variant locus no MR -> candidate analysis
hydronephrosis 0.461 common-variant locus no MR -> candidate analysis
Vertigo 0.427 common-variant locus no MR -> candidate analysis
Parkinson disease 0.427 common-variant locus no MR -> candidate analysis
multiple sclerosis 0.427 common-variant locus no MR -> candidate analysis
injury 0.427 common-variant locus MR: beta=0.843, p=0.0111 (cis)
facial pain 0.35 common-variant locus no MR -> candidate analysis
idiopathic pulmonary fibrosis 0.341 common-variant locus no MR -> candidate analysis
autism 0.182 established (curated) no MR -> candidate analysis
external ear disorder 0.031 common-variant locus no MR -> candidate analysis

Of the 11 rows above, 10 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 M)
gnomAD constraint pLI=1.2e-09, LOEUF=1 — LoF-tolerant
GWAS Catalog 81 unique SNPs / 124 rows
ClinVar 73 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance