CausalSentinel

Protein Dossier — PCOLCE2 (Procollagen C-endopeptidase enhancer 2)

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
Height 0.0308 0.00711 1.47e-05 Wald ratio 1 cis NA
Total cholesterol -0.0427 0.0126 6.83e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol -0.0477 0.0168 0.00465 Wald ratio 1 cis NA
LDL cholesterol -0.0351 0.0128 0.00613 Wald ratio 1 cis NA
Systolic blood pressure automated reading -0.0162 0.00607 0.00756 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux -0.0729 0.0308 0.0178 Wald ratio 1 cis NA
Alcohol intake frequency -0.0189 0.00877 0.0314 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.013 0.00607 0.0326 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine 0.0117 0.00568 0.0397 Wald ratio 1 cis NA
Diagnoses - main ICD10: R11 Nausea and vomiting 0.162 0.0809 0.0451 Wald ratio 1 cis NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate -0.17 0.087 0.0513 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia 0.0702 0.0364 0.0535 Wald ratio 1 cis NA
…and 77 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

30 association rows across 21 traits (28 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
Bone mineral density mean 1e-300 rs138380358 2 GCST90321120 no MR -> candidate analysis
Procollagen C-endopeptidase enhancer 2 levels 4e-192 rs11716897 3 GCST90248895 no MR -> candidate analysis
Serum levels of protein PCOLCE2 4e-94 rs11716897 1 GCST90089278 no MR -> candidate analysis
Endothelin-converting enzyme 1:Extracellular domain levels 1e-69 rs2707975 1 GCST90425830 no MR -> candidate analysis
Height 8e-68 rs2707982 4 GCST90245848 MR: beta=0.0308, p=1.47e-05 (cis)
Procollagen C-endopeptidase enhancer 2 levels (PCOLCE2.6081. 5e-66 rs34516933 1 GCST90242374 no MR -> candidate analysis
Blood protein levels 3e-59 rs4683702 1 GCST006585 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 2e-43 rs12495602 1 GCST90838669 no MR -> candidate analysis
Endothelin-converting enzyme 1 levels (ECE1.3611.70.4) 2e-38 rs4683701 1 GCST90241056 no MR -> candidate analysis
Endothelin-converting enzyme 1 levels 2e-19 rs4683702 2 GCST90100962 no MR -> candidate analysis
Biological Grandparent (maternal): Kidney Disease 1e-11 rs564490873 1 GCST90479684 no MR -> candidate analysis
Pulse pressure 1e-11 rs113546801 2 GCST90018970 no MR -> candidate analysis
…and 9 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 137 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 0.587 common-variant locus no MR -> candidate analysis
Hypercholesterolemia 0.52 common-variant locus MR: beta=-0.0427, p=6.83e-04 (cis)
urinary system disorder 0.488 common-variant locus no MR -> candidate analysis
prolapse of female genital organ 0.488 common-variant locus no MR -> candidate analysis
urethral disorder 0.488 common-variant locus no MR -> candidate analysis
hypertrophic cardiomyopathy 0.46 common-variant locus no MR -> candidate analysis
Genu varum 0.425 common-variant locus no MR -> candidate analysis
Genu valgum 0.425 common-variant locus no MR -> candidate analysis
alcohol drinking 0.407 common-variant locus no MR -> candidate analysis
kidney disorder 0.396 common-variant locus no MR -> candidate analysis
hyperlipidemia 0.058 common-variant locus no MR -> candidate analysis
metabolic disease 0.055 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 11 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=2.1e-13, LOEUF=1.16 — LoF-tolerant
GWAS Catalog 68 unique SNPs / 136 rows
ClinVar 108 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance