CausalSentinel

Protein Dossier — TIRAP (Toll/interleukin-1 receptor domain-containing adapter 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: N92 Excessive frequent and irregular menstruation 0.317 0.0726 1.28e-05 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis 0.267 0.0882 0.0025 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.12 0.0461 0.00904 Wald ratio 1 cis NA
Coronary heart disease -0.156 0.0617 0.0117 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol -0.0971 0.0425 0.0222 Wald ratio 1 cis NA
Cough on most days 0.139 0.0645 0.0317 Wald ratio 1 cis NA
Birth weight -0.0457 0.0219 0.0368 Wald ratio 1 cis NA
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis 0.322 0.155 0.0385 Wald ratio 1 cis NA
Platelet count -5.06 2.51 0.0436 Wald ratio 1 cis NA
Hippocampus volume 55.8 28 0.0465 Wald ratio 1 cis NA
Mean platelet volume 0.0128 0.00648 0.0485 Wald ratio 1 cis NA
Non-cancer illness code self-reported: muscle or soft tissue injuries 0.257 0.133 0.0532 Wald ratio 1 cis NA
…and 76 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

32 association rows across 26 traits (32 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
Height 1e-99 rs8177388 2 GCST90245848 MR: beta=-0.021, p=0.275 (cis)
CD300C/MANSC1 protein level ratio 2e-83 rs8177376 1 GCST90313791 no MR -> candidate analysis
MANSC1/PODXL protein level ratio 1e-68 rs8177376 1 GCST90315372 no MR -> candidate analysis
Toll/interleukin-1 receptor domain-containing adapter protei 5e-60 rs8177399 1 GCST90249882 no MR -> candidate analysis
Serum alkaline phosphatase levels 7e-35 rs8177376 2 GCST90019494 no MR -> candidate analysis
CEACAM8/VNN2 protein level ratio 4e-28 rs8177376 1 GCST90314005 no MR -> candidate analysis
neutrophil (fraction, mean, inv-norm transformed) 8e-26 rs8177391 1 GCST90475538 no MR -> candidate analysis
NPTX1 protein levels 2e-25 rs8177352 1 GCST90470078 no MR -> candidate analysis
Serum levels of protein TIRAP 2e-23 rs8177399 1 GCST90090851 no MR -> candidate analysis
Apolipoprotein B levels 5e-22 rs8177399 2 GCST90019496 no MR -> candidate analysis
Low density lipoprotein cholesterol levels 7e-22 rs8177399 1 GCST90019512 no MR -> candidate analysis
eosinophil (fraction, mean, inv-norm transformed) 7e-22 rs4935964 2 GCST90475300 no MR -> candidate analysis
…and 14 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 203 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
response to statin 0.093 common-variant locus no MR -> candidate analysis
alcohol drinking 0.055 common-variant locus no MR -> candidate analysis
urolithiasis 0.047 common-variant locus no MR -> candidate analysis
lymphatic system disorder 0.041 common-variant locus no MR -> candidate analysis
androgenetic alopecia 0.038 common-variant locus no MR -> candidate analysis
risk-taking behaviour 0.038 common-variant locus no MR -> candidate analysis
stroke disorder 0.031 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 7 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=1.2e-07, LOEUF=1.47 — LoF-tolerant
GWAS Catalog 131 unique SNPs / 327 rows
ClinVar 110 records; 8 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance