CausalSentinel

Protein Dossier — TOR1AIP1 (Torsin-1A-interacting protein 1)

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: high cholesterol 0.0798 0.0309 0.0098 Wald ratio 1 trans NA
Internalizing problems -0.263 0.114 0.0211 Wald ratio 1 trans NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.16 0.0764 0.0362 Wald ratio 1 trans NA
Hippocampus volume 52.2 25.3 0.039 Wald ratio 1 trans NA
Diagnoses - main ICD10: J33 Nasal polyp 0.285 0.138 0.0396 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypopituitarism 0.755 0.368 0.0401 Wald ratio 1 trans NA
Cigarettes smoked per day 0.886 0.432 0.0402 Wald ratio 1 trans NA
Clear cell ovarian cancer 0.424 0.21 0.0432 Wald ratio 1 trans NA
Forced vital capacity (FVC) -0.0196 0.0102 0.0538 Wald ratio 1 trans NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone 0.218 0.114 0.0555 Wald ratio 1 trans NA
Non-cancer illness code self-reported: polio or poliomyelitis 0.558 0.301 0.0637 Wald ratio 1 trans NA
Diagnoses - main ICD10: H25 Senile cataract -0.396 0.222 0.0747 Wald ratio 1 trans NA
…and 84 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

15 association rows across 8 traits (14 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
QSOX1 protein levels 1e-45 rs528065895 1 GCST90470402 no MR -> candidate analysis
TOR1AIP1 protein levels 1e-40 rs141729546 4 GCST90470935 no MR -> candidate analysis
Cerebrospinal fluid protein TOR1AIP1 levels 2e-33 rs538512 1 GCST90944007 no MR -> candidate analysis
Refractive error 3e-10 rs12062341 2 GCST90841196 no MR -> candidate analysis
Prostate cancer 8e-10 rs555526 4 GCST90274713 no MR -> candidate analysis
Thyroid stimulating hormone levels 6e-9 rs571822 1 GCST90572789 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 7e-9 rs7525395 1 GCST90838669 no MR -> candidate analysis
Gut microbial network clusters (BlueViolet (at 3 months) x H 8e-9 rs12139961 1 GCST90569242 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 101 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
autosomal recessive limb-girdle muscular dystrophy type 2Y 0.843 established (curated) no MR -> candidate analysis
TOR1AIP1-related myopathy 0.608 established (curated) no MR -> candidate analysis
centronuclear myopathy 0.559 established (curated) no MR -> candidate analysis
Abnormality of refraction 0.475 common-variant locus no MR -> candidate analysis
aneurysm 0.463 common-variant locus no MR -> candidate analysis
peripheral vascular disease 0.393 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.364 common-variant locus no MR -> candidate analysis
hereditary disease 0.318 established (curated) no MR -> candidate analysis
respiratory tract infectious disorder 0.083 common-variant locus no MR -> candidate analysis

Of the 9 rows above, 9 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 (Torsin-1A-interacting protein 1)
gnomAD constraint pLI=3.4e-16, LOEUF=1.07 — LoF-tolerant
GWAS Catalog 48 unique SNPs / 96 rows
ClinVar 582 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance