CausalSentinel

Protein Dossier — TXNDC15 (Thioredoxin domain-containing protein 15)

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
Height -0.0717 0.014 3.12e-07 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0474 0.00946 5.41e-07 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0378 0.00998 1.52e-04 Wald ratio 1 cis NA
Body mass index (BMI) 0.0421 0.0115 2.54e-04 Wald ratio 1 cis NA
Years of schooling 0.0456 0.0163 0.00511 Wald ratio 1 cis NA
Amyotrophic lateral sclerosis -0.209 0.0866 0.0158 Wald ratio 1 cis NA
Depressive symptoms 0.0358 0.0163 0.0278 Wald ratio 1 cis NA
Alcohol intake frequency 0.0373 0.017 0.0287 Wald ratio 1 cis NA
Sleep duration -0.0196 0.00899 0.0294 Wald ratio 1 cis NA
Neuroblastoma -0.452 0.214 0.035 Wald ratio 1 cis NA
Body fat 0.0534 0.0254 0.0355 Wald ratio 1 cis NA
Diagnoses - main ICD10: N81 Female genital prolapse -0.256 0.127 0.0436 Wald ratio 1 cis 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

9 association rows across 7 traits (7 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
TXNDC15 protein levels 2e-66 rs184061578 3 GCST90470990 no MR -> candidate analysis
Serum levels of protein TXNDC15 2e-26 rs3733897 1 GCST90089370 no MR -> candidate analysis
Physical function (baseline) 2e-11 rs11950533 1 GCST90565837 no MR -> candidate analysis
Bioavailable testosterone levels 4e-9 rs3733897 1 GCST90012103 no MR -> candidate analysis
Parkinson’s disease or first degree relation to individual w 7e-9 rs11950533 1 GCST009325 no MR -> candidate analysis
Congenital solitary functioning kidney 6e-8 rs73282857 1 GCST90244792 no MR -> candidate analysis
Type 2 diabetes 2e-6 rs319598 1 GCST002352 MR: beta=0.0645, p=0.187 (cis)

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

Top diseases by Open Targets association (of 82 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
meckel syndrome 14 0.817 established (curated) no MR -> candidate analysis
Meckel syndrome 0.702 established (curated) no MR -> candidate analysis
hereditary disease 0.316 established (curated) no MR -> candidate analysis
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 0.195 established (curated) no MR -> candidate analysis

Of the 4 rows above, 4 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=3.2e-06, LOEUF=0.963 — LoF-tolerant
GWAS Catalog 37 unique SNPs / 74 rows
ClinVar 111 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance