CausalSentinel

Protein Dossier — PAM (Peptidyl-glycine alpha-amidating monooxygenase)

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
Sleep duration -0.0192 0.00422 5.23e-06 Wald ratio 1 cis NA
Rheumatoid arthritis 0.105 0.0262 6.43e-05 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain 0.077 0.0242 0.00147 Wald ratio 1 cis NA
Body mass index (BMI) -0.017 0.00541 0.00162 Wald ratio 1 cis NA
2hr glucose -0.127 0.0429 0.00318 Wald ratio 1 cis NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] -0.151 0.0525 0.00407 Wald ratio 1 cis NA
Height 0.0191 0.00665 0.00409 Wald ratio 1 cis NA
Years of schooling -0.0236 0.00858 0.00596 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia -0.0949 0.0364 0.00911 Wald ratio 1 cis NA
Eczema -0.0946 0.0377 0.0121 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.0567 0.0227 0.0126 Wald ratio 1 cis NA
Endometrioid ovarian cancer 0.153 0.0648 0.0184 Wald ratio 1 cis NA
…and 110 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

241 association rows across 101 traits (224 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 PAM levels 1e-1412 rs35658696 4 GCST90860454 no MR -> candidate analysis
Peptidyl-glycine alpha-amidating monooxygenase levels 2e-485 rs35658696 3 GCST90248972 no MR -> candidate analysis
Bone mineral density mean 1e-300 rs564274583 59 GCST90321120 no MR -> candidate analysis
SCGB3A1 protein levels 3e-132 rs2432162 1 GCST90470542 no MR -> candidate analysis
Serum levels of protein PAM 1e-126 rs116782923 2 GCST90089098 no MR -> candidate analysis
PAM protein levels 3e-80 rs2059211 3 GCST90470156 no MR -> candidate analysis
Peptidyl-glycine alpha-amidating monooxygenase levels (PAM.5 4e-77 rs41300805 3 GCST90242214 no MR -> candidate analysis
Type 2 diabetes 3e-45 rs78408340 16 GCST90492734 MR: beta=-0.161, p=0.0495 (cis)
Height 1e-42 rs11952361 8 GCST90245848 MR: beta=0.0191, p=0.00409 (cis)
Type 2 diabetes (PheCode 250.2) 1e-35 rs78408340 2 GCST90475667 no MR -> candidate analysis
Diabetes mellitus (PheCode 250) 1e-34 rs78408340 2 GCST90475658 no MR -> candidate analysis
PR interval 2e-29 rs114555443 2 GCST010321 no MR -> candidate analysis
…and 89 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 184 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
type 2 diabetes mellitus 0.757 0.339 multi-layer: burden+GWAS (allelic-series candidate) no MR -> candidate analysis
diabetes mellitus 0.879 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.838 common-variant locus no MR -> candidate analysis
diabetic retinopathy 0.709 common-variant locus no MR -> candidate analysis
diabetic eye disease 0.703 common-variant locus no MR -> candidate analysis
diabetic neuropathy 0.692 common-variant locus no MR -> candidate analysis
androgenetic alopecia 0.667 common-variant locus no MR -> candidate analysis
intelligence 0.664 common-variant locus no MR -> candidate analysis
mathematical ability 0.63 common-variant locus no MR -> candidate analysis
type 1 diabetes mellitus 0.604 common-variant locus no MR -> candidate analysis
insomnia 0.602 common-variant locus no MR -> candidate analysis
Chest pain 0.511 common-variant locus MR: beta=0.022, p=0.352 (cis)
myocardial infarction 0.51 common-variant locus MR: beta=0.0231, p=0.336 (cis)
urolithiasis 0.507 common-variant locus no MR -> candidate analysis
alcohol drinking 0.507 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), 1 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 (Peptidyl-glycine alpha-amidating monooxygenase)
gnomAD constraint pLI=6.4e-13, LOEUF=0.718 — LoF-tolerant
GWAS Catalog 151 unique SNPs / 363 rows
ClinVar 159 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance