CausalSentinel

Protein Dossier — PMEL (Melanocyte protein PMEL)

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: asthma 0.163 0.0333 1.01e-06 Wald ratio 1 trans NA
Weight 0.0498 0.0124 5.52e-05 Wald ratio 1 trans NA
Non-cancer illness code self-reported: vitiligo 1.12 0.31 3.24e-04 Wald ratio 1 trans NA
Forced vital capacity (FVC) 0.041 0.0115 3.58e-04 Wald ratio 1 trans NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation 0.22 0.0788 0.00526 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) 0.0323 0.0121 0.00767 Wald ratio 1 trans NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus 0.254 0.0969 0.00869 Wald ratio 1 trans NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.245 0.0958 0.0106 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.133 0.0546 0.0146 Wald ratio 1 trans NA
Myocardial infarction 0.205 0.0897 0.0225 Wald ratio 1 trans NA
Heel bone mineral density (BMD) T-score automated 0.0384 0.018 0.0331 Wald ratio 1 trans NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] -0.293 0.138 0.0344 Wald ratio 1 trans NA
…and 64 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

9 association rows across 9 traits (9 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
Melanocyte protein PMEL levels 5e-27 rs2069398 1 GCST90249044 no MR -> candidate analysis
Serum levels of protein PMEL 4e-22 rs12309895 1 GCST90089451 no MR -> candidate analysis
Whole body water mass (UKB data field 23102) 4e-17 rs2069408 1 GCST90468184 no MR -> candidate analysis
Basal metabolic rate (UKB data field 23105) 2e-16 rs2069408 1 GCST90468159 no MR -> candidate analysis
Blood protein levels 2e-13 rs3213122 1 GCST006585 no MR -> candidate analysis
Whole body fat free mass (UKB data field 23101) 2e-11 rs2069408 1 GCST90428120 no MR -> candidate analysis
Circulating DNER levels 4e-11 rs2069408 1 GCST90860417 no MR -> candidate analysis
Asthma 1e-10 rs2069408 1 GCST001183 MR: beta=0.163, p=1.01e-06 (trans)
Refractive error 8e-10 rs2069408 1 GCST90841196 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 851 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
autoimmune disease 0.142 common-variant locus no MR -> candidate analysis

Of the 1 rows above, 1 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 2 known modulators (Melanocyte protein PMEL)
gnomAD constraint pLI=3e-15, LOEUF=1.03 — LoF-tolerant
GWAS Catalog 61 unique SNPs / 120 rows
ClinVar 104 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance