CausalSentinel

Protein Dossier — QPCTL (Glutaminyl-peptide cyclotransferase-like protein)

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
Non-cancer illness code self-reported: enlarged prostate 0.22 0.0613 3.28e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: K35 Acute appendicitis 0.324 0.0934 5.23e-04 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0242 0.0073 9.33e-04 Wald ratio 1 cis NA
Myocardial infarction -0.133 0.0417 0.00146 Wald ratio 1 cis NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.196 0.0636 0.00209 Wald ratio 1 cis NA
Coronary heart disease -0.113 0.0376 0.00263 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol -0.0734 0.0259 0.00464 Wald ratio 1 cis NA
Sodium in urine -0.0231 0.00876 0.0082 Wald ratio 1 cis NA
Body mass index (BMI) -0.0231 0.00889 0.00954 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma 0.0579 0.0235 0.0139 Wald ratio 1 cis NA
Systolic blood pressure automated reading 0.0224 0.00911 0.0139 Wald ratio 1 cis NA
Diagnoses - main ICD10: K80 Cholelithiasis -0.179 0.0745 0.0166 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

55 association rows across 30 traits (44 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
Glutaminyl-peptide cyclotransferase-like protein levels 7e-88 rs17850756 2 GCST90247790 no MR -> candidate analysis
Serum levels of protein QPCTL 3e-35 rs17850756 1 GCST90090347 no MR -> candidate analysis
Body mass index 4e-30 rs57925894 11 GCST90662887 MR: beta=-0.0231, p=0.00954 (cis)
Glutaminyl-peptide cyclotransferase-like protein levels (QPC 2e-28 rs17850756 1 GCST90241277 no MR -> candidate analysis
Whole body fat mass (UKB data field 23100) 1e-21 rs2287019 1 GCST90428121 no MR -> candidate analysis
Waist-hip ratio 1e-19 rs2287019 3 GCST008998 no MR -> candidate analysis
Blood protein levels 5e-19 rs7256197 1 GCST006585 no MR -> candidate analysis
Glucose levels (UKB data field 30740) 5e-15 rs7256920 1 GCST90468071 no MR -> candidate analysis
Waist circumference 2e-14 rs2287019 3 GCST004065 no MR -> candidate analysis
Retinal arteriolar tortuosity 1e-13 rs11673709 1 GCST90270397 no MR -> candidate analysis
LDL cholesterol levels 7e-13 rs150184119 2 GCST90244006 no MR -> candidate analysis
Pulse pressure 2e-12 rs74889068 3 GCST90132905 no MR -> candidate analysis
…and 18 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 55 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
myocardial infarction 0.435 common-variant locus MR: beta=-0.133, p=0.00146 (cis)
response to statin 0.363 common-variant locus no MR -> candidate analysis
sleep disorder 0.251 common-variant locus MR: beta=0.13, p=0.207 (cis)
Abnormality of the skeletal system 0.226 common-variant locus no MR -> candidate analysis
obesity disorder 0.103 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.073 common-variant locus no MR -> candidate analysis
smoking behavior 0.068 common-variant locus no MR -> candidate analysis
nephrolithiasis 0.067 common-variant locus no MR -> candidate analysis
myotonic syndrome 0.058 common-variant locus no MR -> candidate analysis
diabetic eye disease 0.049 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.048 common-variant locus no MR -> candidate analysis
coronary atherosclerosis 0.045 common-variant locus no MR -> candidate analysis

Of the 12 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 (Glutaminyl-peptide cyclotransferase-like protein)
gnomAD constraint pLI=3.4e-10, LOEUF=1.21 — LoF-tolerant
GWAS Catalog 116 unique SNPs / 278 rows
ClinVar 106 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance