CausalSentinel

Protein Dossier — TXNDC5 (Thioredoxin domain-containing protein 5)

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
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 1.66 0.445 1.87e-04 Wald ratio 1 trans NA
Cigarettes smoked per day 2.05 0.597 5.82e-04 Wald ratio 1 trans NA
Vascular or heart problems diagnosed by doctor: Angina 0.104 0.0426 0.0145 Wald ratio 1 trans NA
Cancer code self-reported: prostate cancer 0.192 0.0819 0.0189 Wald ratio 1 trans NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain 0.0848 0.0374 0.0234 Wald ratio 1 trans NA
Age at menopause -0.302 0.134 0.0244 Wald ratio 1 trans NA
Birth weight 0.0302 0.0134 0.0244 Wald ratio 1 trans NA
Lumbar spine bone mineral density 0.0656 0.0313 0.0364 Wald ratio 1 trans NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus 0.133 0.0653 0.0413 Wald ratio 1 trans NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.131 0.0642 0.0418 Wald ratio 1 trans NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate 0.177 0.0873 0.0424 Wald ratio 1 trans NA
Subjective well being -0.0268 0.0134 0.0455 Wald ratio 1 trans NA
…and 92 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

72 association rows across 52 traits (62 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
Bone mineral density mean 1e-300 rs116769360 1 GCST90321120 no MR -> candidate analysis
RWDD1/TXNDC5 protein level ratio 2e-138 rs11962800 1 GCST90315796 no MR -> candidate analysis
LGALS8/TXNDC5 protein level ratio 5e-135 rs11962800 1 GCST90315321 no MR -> candidate analysis
MCFD2/TXNDC5 protein level ratio 5e-127 rs11962800 1 GCST90315410 no MR -> candidate analysis
ENO2/TXNDC5 protein level ratio 5e-108 rs11962800 1 GCST90314671 no MR -> candidate analysis
CRELD2/TXNDC5 protein level ratio 2e-96 rs11962800 1 GCST90314259 no MR -> candidate analysis
NUCB2/TXNDC5 protein level ratio 2e-95 rs11962800 1 GCST90315578 no MR -> candidate analysis
PARK7/TXNDC5 protein level ratio 9e-89 rs11962800 1 GCST90315600 no MR -> candidate analysis
Circulating TXNDC5 levels 1e-80 rs111331197 3 GCST90860383 no MR -> candidate analysis
SEMA4D/TXNDC5 protein level ratio 9e-79 rs11962800 1 GCST90315824 no MR -> candidate analysis
LBR/TXNDC5 protein level ratio 5e-77 rs11962800 1 GCST90315304 no MR -> candidate analysis
PTPN6/TXNDC5 protein level ratio 2e-74 rs11962800 1 GCST90315749 no MR -> candidate analysis
…and 40 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 226 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
colorectal carcinoma 0.48 common-variant locus no MR -> candidate analysis
spinal stenosis 0.273 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.111 common-variant locus no MR -> candidate analysis
kidney cancer 0.085 common-variant locus no MR -> candidate analysis
Abnormal nasolacrimal system morphology 0.085 common-variant locus no MR -> candidate analysis
spermatocele 0.072 common-variant locus no MR -> candidate analysis

Of the 6 rows above, 6 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 (Thioredoxin domain-containing protein 5)
gnomAD constraint pLI=3.8e-13, LOEUF=1.08 — LoF-tolerant
GWAS Catalog 109 unique SNPs / 184 rows
ClinVar 105 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance