CausalSentinel

Protein Dossier — QPCT (Glutaminyl-peptide cyclotransferase)

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
Schizophrenia 0.131 0.0391 7.85e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0457 0.0145 0.00162 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0335 0.0115 0.0036 Wald ratio 1 cis NA
Alzheimer’s disease -0.167 0.059 0.00473 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.232 0.097 0.017 Wald ratio 1 cis NA
Forearm bone mineral density 0.134 0.0575 0.0196 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.0729 0.0324 0.0245 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt -0.308 0.137 0.0249 Wald ratio 1 cis NA
Sodium in urine -0.0192 0.00875 0.028 Wald ratio 1 cis NA
Eye problems or disorders: Diabetes related eye disease -0.375 0.171 0.0285 Wald ratio 1 cis NA
Lung adenocarcinoma 0.232 0.109 0.0334 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux -0.099 0.0474 0.0366 Wald ratio 1 cis NA
…and 68 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

54 association rows across 29 traits (46 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
Circulating QPCT levels 3e-440 rs2255991 4 GCST90860490 no MR -> candidate analysis
QPCT protein levels 1e-199 rs72792854 5 GCST90470401 no MR -> candidate analysis
Height 3e-90 rs7593932 8 GCST90245848 no MR -> candidate analysis
Cerebrospinal fluid protein QPCT levels 9e-79 rs12467820 1 GCST90944879 no MR -> candidate analysis
Glutaminyl-peptide cyclotransferase levels 5e-60 rs12467820 2 GCST90427104 no MR -> candidate analysis
Serum levels of protein QPCT 2e-33 rs12467820 1 GCST90089874 no MR -> candidate analysis
Pyroglutamylglutamine levels 9e-31 rs77684493 1 GCST90140299 no MR -> candidate analysis
Blood protein levels 4e-28 rs13027919 1 GCST006585 no MR -> candidate analysis
Systolic blood pressure 5e-20 rs13419498 2 GCST90310294 MR: beta=0.0082, p=0.367 (cis)
Systolic blood pressure (MTAG) 1e-17 rs6734118 1 GCST90449056 no MR -> candidate analysis
Fasting blood glucose 2e-15 rs13027919 1 GCST90662896 no MR -> candidate analysis
Diastolic blood pressure 2e-13 rs13419498 1 GCST90310295 no MR -> candidate analysis
…and 17 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 160 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
Alzheimer disease 0.039 common-variant locus no MR -> candidate analysis
schizophrenia 0.502 common-variant locus MR: beta=0.131, p=7.85e-04 (cis)
head injury 0.416 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.212 common-variant locus no MR -> candidate analysis
response to xenobiotic stimulus 0.188 common-variant locus no MR -> candidate analysis
Hallux valgus 0.111 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.1 common-variant locus MR: beta=0.0791, p=0.313 (cis)
heart failure 0.092 common-variant locus no MR -> candidate analysis
premature birth 0.092 common-variant locus no MR -> candidate analysis
essential hypertension 0.091 common-variant locus no MR -> candidate analysis
alcohol drinking 0.09 common-variant locus no MR -> candidate analysis
COVID-19 0.078 common-variant locus no MR -> candidate analysis
esophageal ulcer 0.078 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.076 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.061 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 13 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)
gnomAD constraint pLI=1.1e-15, LOEUF=1.3 — LoF-tolerant
GWAS Catalog 71 unique SNPs / 142 rows
ClinVar 106 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance