CausalSentinel

Protein Dossier — PMP2 (Myelin P2 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
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.503 0.157 0.00134 Wald ratio 1 trans NA
Non-cancer illness code self-reported: joint disorder 0.436 0.166 0.00862 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension -0.0743 0.0312 0.0173 Wald ratio 1 trans NA
Lumbar spine bone mineral density -0.135 0.0605 0.0255 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hiatus hernia -0.35 0.163 0.0324 Wald ratio 1 trans NA
Thalamus volume 92.1 43.4 0.0338 Wald ratio 1 trans NA
Sodium in urine 0.0336 0.0167 0.0446 Wald ratio 1 trans NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.25 0.128 0.05 Wald ratio 1 trans NA
Non-cancer illness code self-reported: asthma 0.0843 0.0438 0.0544 Wald ratio 1 trans NA
Eye problems or disorders: Glaucoma 0.223 0.116 0.0546 Wald ratio 1 trans NA
Cancer code self-reported: malignant melanoma 0.279 0.15 0.0625 Wald ratio 1 trans NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities -0.293 0.164 0.0746 Wald ratio 1 trans NA
…and 70 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

12 association rows across 11 traits (3 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 FABP9 levels 6e-11 rs569513636 1 GCST90860324 no MR -> candidate analysis
Cerebrospinal fluid protein FABP5 levels 6e-10 rs16908973 1 GCST90944294 no MR -> candidate analysis
Lymphocytic thyroiditis 4e-8 rs144209445 1 GCST90627755 no MR -> candidate analysis
Cutaneous mastocytosis (childhood) 6e-8 rs1909936 1 GCST011379 no MR -> candidate analysis
Memory performance 3e-6 rs13252768 2 GCST90448843 no MR -> candidate analysis
Memory performance (excluding comorbidities) 5e-6 rs13252768 1 GCST90448856 no MR -> candidate analysis
Overall survival in serous epithelial ovarian cancer treated 6e-6 rs202280 1 GCST004896 no MR -> candidate analysis
Type 2 diabetes 6e-6 rs182719694 1 GCST004774 no MR -> candidate analysis
Night sleep phenotypes 7e-6 rs71519017 1 GCST003542 no MR -> candidate analysis
Stuttering 9e-6 rs146347922 1 GCST90707227 no MR -> candidate analysis
Baseline memory 9e-6 rs13252768 1 GCST90448433 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 91 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
Charcot-Marie-Tooth disease type 1G 0.846 established (curated) no MR -> candidate analysis
peripheral neuropathy 0.547 established (curated) no MR -> candidate analysis
hereditary disease 0.551 established (curated) no MR -> candidate analysis
Charcot-Marie-Tooth disease type 1E 0.195 established (curated) no MR -> candidate analysis
Hashimoto thyroiditis 0.138 common-variant locus no MR -> candidate analysis

Of the 5 rows above, 5 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 (Myelin P2 protein)
gnomAD constraint pLI=0.0018, LOEUF=1.14 — LoF-tolerant
GWAS Catalog 31 unique SNPs / 55 rows
ClinVar 183 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance