CausalSentinel

Protein Dossier — PCOLCE (Procollagen C-endopeptidase enhancer 1)

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
Red blood cell count -0.104 0.0118 1.95e-18 Wald ratio 1 cis NA
Mean cell haemoglobin 0.461 0.0549 4.60e-17 Wald ratio 1 cis NA
Mean cell volume 1.03 0.138 7.57e-14 Wald ratio 1 cis NA
Iron 0.264 0.0487 6.38e-08 Wald ratio 1 cis NA
Transferrin Saturation 0.258 0.0492 1.52e-07 Wald ratio 1 cis 0.883
Packed cell volume -0.467 0.0956 1.05e-06 Wald ratio 1 cis NA
Mean cell haemoglobin concentration 0.0672 0.018 1.86e-04 Wald ratio 1 cis NA
Height 0.0568 0.0166 6.07e-04 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated -0.0513 0.0152 7.35e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: joint disorder 0.367 0.121 0.00241 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.0339 0.0112 0.00252 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.0355 0.012 0.00315 Wald ratio 1 cis NA
…and 107 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

16 association rows across 14 traits (12 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
Hematological traits (multi-trait analysis) 1e-113 rs11970888 1 GCST90838669 no MR -> candidate analysis
Circulating PCOLCE levels 1e-35 rs537022088 1 GCST90860486 no MR -> candidate analysis
LRCH4 protein levels 6e-19 rs62482223 1 GCST90469791 no MR -> candidate analysis
Pyruvate levels 2e-15 rs62482222 1 GCST90501232 no MR -> candidate analysis
PILRB protein levels 6e-14 rs112685211 1 GCST90470237 no MR -> candidate analysis
Mean corpuscular haemoglobin (UKB data field 30050) 1e-13 rs112888745 1 GCST90468084 no MR -> candidate analysis
Degree of unsaturation 9e-12 rs2734895 1 GCST90501284 no MR -> candidate analysis
Height 6e-10 rs2272575 1 GCST90245848 MR: beta=0.0568, p=6.07e-04 (cis)
Height (baseline) 2e-9 rs34048349 1 GCST90565843 no MR -> candidate analysis
Unsupervised deep imaging phenotypes (UDIP-FA) 9e-9 rs62482222 1 GCST90860937 no MR -> candidate analysis
Stool frequency 1e-8 rs62482222 3 GCST90002250 no MR -> candidate analysis
High-density lipoprotein levels (MTAG) 3e-8 rs2734895 1 GCST90179147 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 564 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
anemia (phenotype) 0.124 common-variant locus no MR -> candidate analysis
hair color 0.123 common-variant locus no MR -> candidate analysis
anemia 0.104 common-variant locus no MR -> candidate analysis
polycythemia 0.093 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 4 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 (Bone morphogenetic protein 1)
gnomAD constraint pLI=2.3e-08, LOEUF=0.934 — LoF-tolerant
GWAS Catalog 108 unique SNPs / 240 rows
ClinVar 111 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance