CausalSentinel

Protein Dossier — TNFRSF10B (Tumor necrosis factor receptor superfamily member 10B)

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: joint disorder 0.521 0.16 0.00109 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol -0.183 0.0582 0.00163 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension -0.0873 0.0332 0.00866 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia -0.468 0.181 0.00985 Wald ratio 1 cis NA
Hirschsprung’s disease -2.36 0.93 0.0112 Wald ratio 1 cis NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.439 0.177 0.0131 Wald ratio 1 cis NA
Low grade serous ovarian cancer -0.847 0.372 0.0227 Wald ratio 1 cis NA
Sodium in urine -0.0379 0.0176 0.0308 Wald ratio 1 cis NA
Weight -0.0321 0.0158 0.0418 Wald ratio 1 cis NA
Body mass index (BMI) -0.0352 0.0178 0.0485 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities -0.355 0.185 0.0555 Wald ratio 1 cis NA
Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level 0.536 0.288 0.0629 Wald ratio 1 cis NA
…and 48 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

95 association rows across 70 traits (85 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
Circulating TNFRSF10B levels 6e-794 rs7841989 3 GCST90859758 no MR -> candidate analysis
Circulating TNFRSF10C levels 6e-588 rs149683200 2 GCST90859942 no MR -> candidate analysis
TNF-related apoptosis-inducing ligand receptor 2 levels 1e-172 rs2293400 4 GCST90012021 no MR -> candidate analysis
TNFRSF10B protein levels 1e-130 rs35974498 7 GCST90470900 no MR -> candidate analysis
Cerebrospinal fluid protein TNFRSF10B levels 4e-90 rs4871844 1 GCST90943992 no MR -> candidate analysis
Tumor necrosis factor receptor superfamily member 10B levels 1e-85 rs4871844 1 GCST90427023 no MR -> candidate analysis
Circulating TNFSF10 levels (id: OID00488_OID20611) 2e-22 rs149683200 3 GCST90859847 no MR -> candidate analysis
monocyte (fraction, mean, inv-norm transformed) 2e-21 rs4871844 2 GCST90475511 no MR -> candidate analysis
Circulating TNFSF10 levels (id: OID00672_OID20611) 2e-21 rs149683200 3 GCST90860016 no MR -> candidate analysis
Aspartate aminotransferase levels (UKB data field 30650) 4e-21 rs4871844 1 GCST90468063 no MR -> candidate analysis
Cerebrospinal fluid protein TNFRSF10C levels 1e-20 rs143033493 1 GCST90944917 no MR -> candidate analysis
TNFRSF10A protein levels 3e-20 rs56108503 2 GCST90470899 no MR -> candidate analysis
…and 58 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 534 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
basal cell carcinoma 0.762 common-variant locus MR: beta=-0.987, p=0.394 (cis)
head and neck squamous cell carcinoma 0.657 established (curated) no MR -> candidate analysis
Iron deficiency anemia 0.637 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.636 common-variant locus no MR -> candidate analysis
renal carcinoma 0.536 common-variant locus no MR -> candidate analysis
clear cell renal carcinoma 0.401 established (curated) no MR -> candidate analysis
vascular disorder 0.476 common-variant locus no MR -> candidate analysis
intestinal disorder 0.476 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.418 common-variant locus no MR -> candidate analysis
non-melanoma skin carcinoma 0.412 common-variant locus no MR -> candidate analysis
skin cancer 0.307 common-variant locus no MR -> candidate analysis
bipolar disorder 0.291 common-variant locus no MR -> candidate analysis
jaw disease 0.291 common-variant locus no MR -> candidate analysis
placenta praevia 0.287 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.238 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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 7 known modulators (Tumor necrosis factor receptor superfamily member 10B)
gnomAD constraint pLI=8.5e-11, LOEUF=1.12 — LoF-tolerant
GWAS Catalog 100 unique SNPs / 200 rows
ClinVar 188 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance