CausalSentinel

Protein Dossier — MLN (Promotilin)

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
Body mass index (BMI) 0.0515 0.0127 4.85e-05 Wald ratio 1 trans NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.251 0.0755 8.91e-04 Wald ratio 1 trans NA
Weight 0.0299 0.0112 0.00754 Wald ratio 1 trans NA
Diagnoses - main ICD10: J33 Nasal polyp 0.352 0.132 0.00787 Wald ratio 1 trans NA
Eye problems or disorders: Glaucoma -0.461 0.174 0.00817 Wald ratio 1 trans NA
Fasting proinsulin -0.0953 0.0361 0.0082 Wald ratio 1 trans NA
Fasting glucose -0.0373 0.0157 0.0179 Wald ratio 1 trans NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.16 0.0703 0.0226 Wald ratio 1 trans NA
Percent emphysema -0.105 0.046 0.0227 Wald ratio 1 trans NA
Fractured bone site(s): Ankle 0.194 0.09 0.0315 Wald ratio 1 trans NA
Neo-openness to experience -0.79 0.37 0.0329 Wald ratio 1 trans NA
Transferrin Saturation -0.108 0.053 0.0414 Wald ratio 1 trans NA
…and 90 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

78 association rows across 51 traits (71 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
MLN/TNFRSF12A protein level ratio 4e-737 rs2894342 1 GCST90315459 no MR -> candidate analysis
Promotilin levels 3e-266 rs9357165 2 GCST90249112 no MR -> candidate analysis
MLN protein levels 6e-134 rs34929964 5 GCST90469913 no MR -> candidate analysis
Serum levels of protein MLN 2e-118 rs73412140 1 GCST90089107 no MR -> candidate analysis
Bone mineral density mean 7e-112 rs114588989 1 GCST90321120 no MR -> candidate analysis
Platelet crit (UKB data field 30090) 5e-94 rs35483019 1 GCST90468096 no MR -> candidate analysis
Promotilin levels (MLN.5631.83.3) 4e-90 rs147640352 2 GCST90242398 no MR -> candidate analysis
Blood protein levels 4e-79 rs2395400 1 GCST006585 no MR -> candidate analysis
TNXB protein levels 2e-26 rs3998110 1 GCST90470930 no MR -> candidate analysis
Body mass index 5e-23 rs2894342 7 GCST90255621 MR: beta=0.0515, p=4.85e-05 (trans)
Physical function (baseline) 9e-23 rs1547668 2 GCST90565837 no MR -> candidate analysis
CHMP1A/PTPN6 protein level ratio 9e-16 rs2281816 1 GCST90314052 no MR -> candidate analysis
…and 39 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 298 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
rheumatoid arthritis 0.674 common-variant locus MR: beta=-0.126, p=0.148 (trans)
Graves disease 0.628 common-variant locus no MR -> candidate analysis
celiac disease 0.613 common-variant locus no MR -> candidate analysis
Pain 0.594 common-variant locus no MR -> candidate analysis
type 1 diabetes mellitus 0.556 common-variant locus no MR -> candidate analysis
Knee pain 0.511 common-variant locus no MR -> candidate analysis
ulcerative colitis 0.463 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.451 common-variant locus no MR -> candidate analysis
lichen sclerosus et atrophicus 0.452 common-variant locus no MR -> candidate analysis
gastric carcinoma 0.445 common-variant locus no MR -> candidate analysis
familial glucocorticoid deficiency 0.441 common-variant locus no MR -> candidate analysis
gastritis 0.413 common-variant locus MR: beta=0.16, p=0.0226 (trans)
Shoulder pain 0.415 common-variant locus no MR -> candidate analysis
Neck pain 0.415 common-variant locus no MR -> candidate analysis
duodenitis 0.413 common-variant locus MR: beta=0.16, p=0.0226 (trans)

Of the 15 rows above, 12 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 (Promotilin)
gnomAD constraint pLI=8.3e-06, LOEUF=1.64 — LoF-tolerant
GWAS Catalog 139 unique SNPs / 346 rows
ClinVar 26 records; 5 pathogenic in sample of 26
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance