CausalSentinel

Protein Dossier — PENK (Proenkephalin-A)

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 -0.0322 0.00623 2.31e-07 Wald ratio 1 cis 3.2e-32
Sodium in urine 0.0162 0.0051 0.00145 Wald ratio 1 cis NA
Platelet count 2.62 0.856 0.00225 Wald ratio 1 cis NA
Happiness 0.019 0.00641 0.00299 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0132 0.00448 0.00318 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0148 0.0053 0.00518 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.0848 0.0308 0.00588 Wald ratio 1 cis NA
Bulimia nervosa -0.0473 0.0172 0.00596 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate 0.106 0.0399 0.00784 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0102 0.00425 0.0162 Wald ratio 1 cis NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.149 0.0622 0.0163 Wald ratio 1 cis NA
Body mass index (BMI) 0.0111 0.00518 0.0313 Wald ratio 1 cis NA
…and 101 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

58 association rows across 34 traits (56 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
Proenkephalin-A levels 1e-236 rs34217211 2 GCST90248943 no MR -> candidate analysis
Height 1e-141 rs2609996 5 GCST90245848 MR: beta=-0.0322, p=2.31e-07 (cis)
Serum levels of protein PENK 2e-128 rs2576575 1 GCST90090491 no MR -> candidate analysis
Proenkephalin-A levels (PENK.9076.25.3) 1e-87 rs2670014 2 GCST90242379 no MR -> candidate analysis
Blood protein levels 8e-70 rs2670014 1 GCST006585 no MR -> candidate analysis
Height (baseline) 1e-51 rs34242338 4 GCST90565843 no MR -> candidate analysis
Physical function (baseline) 9e-30 rs34242338 4 GCST90565837 no MR -> candidate analysis
Educational attainment 8e-24 rs1866823 2 GCST90105038 no MR -> candidate analysis
Whole body fat free mass (UKB data field 23101) 3e-15 rs34242338 2 GCST90428120 no MR -> candidate analysis
Educational attainment (years of education) 3e-14 rs2246873 2 GCST006442 no MR -> candidate analysis
Smoking initiation 3e-14 rs2670012 2 GCST90243985 no MR -> candidate analysis
Educational attainment (MTAG) 5e-14 rs1866823 1 GCST006571 no MR -> candidate analysis
…and 22 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 327 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 0.744 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.477 common-variant locus no MR -> candidate analysis
smoking initiation 0.438 common-variant locus no MR -> candidate analysis
alcohol drinking 0.42 common-variant locus no MR -> candidate analysis
urolithiasis 0.411 common-variant locus no MR -> candidate analysis
brain aneurysm 0.387 common-variant locus no MR -> candidate analysis
substance-related disorder 0.35 common-variant locus no MR -> candidate analysis
diabetic ketoacidosis 0.334 common-variant locus no MR -> candidate analysis

Of the 8 rows above, 8 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=1.7e-09, LOEUF=1.45 — LoF-tolerant
GWAS Catalog 49 unique SNPs / 98 rows
ClinVar 89 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance