Protein Dossier — TNFRSF1B (Tumor necrosis factor receptor superfamily member 1B)
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 |
| Eye problems or disorders: Injury or trauma resulting in loss of vision |
0.416 |
0.113 |
2.29e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema |
0.161 |
0.049 |
0.00105 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I83 Varicose veins of lower extremities |
0.227 |
0.0723 |
0.0017 |
Wald ratio |
1 |
cis |
NA |
| Forearm bone mineral density |
0.209 |
0.0836 |
0.0125 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.1 |
0.0429 |
0.0199 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K29 Gastritis and duodenitis |
-0.251 |
0.109 |
0.0213 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: chronic obstructive airways disease or copd |
0.359 |
0.159 |
0.0245 |
Wald ratio |
1 |
cis |
NA |
| Bulimia nervosa |
-0.0989 |
0.0442 |
0.0252 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: high cholesterol |
0.0664 |
0.0327 |
0.0425 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: asthma |
0.0666 |
0.0339 |
0.0494 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: diverticular disease or diverticulitis |
-0.342 |
0.179 |
0.056 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms |
-0.256 |
0.139 |
0.0658 |
Wald ratio |
1 |
cis |
NA |
| …and 94 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3152_57_1 |
TNF sR-II |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
30 association rows across 19 traits (26 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 |
| TNFRSF1A/TNFRSF1B protein level ratio |
3e-439 |
rs5746012 |
1 |
GCST90315937 |
no MR -> candidate analysis |
| HAVCR2/TNFRSF1B protein level ratio |
7e-310 |
rs5746026 |
1 |
GCST90315030 |
no MR -> candidate analysis |
| PIK3IP1/TNFRSF1B protein level ratio |
1e-266 |
rs5746012 |
1 |
GCST90315654 |
no MR -> candidate analysis |
| Circulating TNFRSF1B levels |
2e-188 |
rs5746017 |
4 |
GCST90859916 |
no MR -> candidate analysis |
| TNFRSF1B protein levels |
5e-128 |
rs5746017 |
3 |
GCST90470911 |
no MR -> candidate analysis |
| Tumor necrosis factor receptor 2 levels |
5e-50 |
rs5746026 |
2 |
GCST90012026 |
no MR -> candidate analysis |
| Tumor necrosis factor receptor superfamily member 1B levels |
4e-38 |
rs5746011 |
2 |
GCST90249840 |
no MR -> candidate analysis |
| Eosinophil count |
8e-22 |
rs474247 |
2 |
GCST007065 |
no MR -> candidate analysis |
| Hypothyroidism |
3e-20 |
rs235220 |
4 |
GCST90627750 |
MR: beta=0.161, p=0.00105 (cis) |
| Autoimmune hypothyroidism |
1e-17 |
rs235220 |
1 |
GCST90837324 |
no MR -> candidate analysis |
| Eosinophil percentage of white cells |
6e-17 |
rs474247 |
1 |
GCST90002382 |
no MR -> candidate analysis |
| Tumor necrosis factor receptor superfamily member 1B levels |
3e-15 |
rs5746017 |
1 |
GCST90243171 |
no MR -> candidate analysis |
| …and 7 more traits (see JSON) |
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4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 939 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 |
| hypothyroidism |
0.664 |
— |
common-variant locus |
MR: beta=0.161, p=0.00105 (cis) |
| thyroid gland disorder |
0.487 |
— |
common-variant locus |
no MR -> candidate analysis |
| childhood onset asthma |
0.346 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 3 rows above, 2 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 (Tumor necrosis factor receptor superfamily member 1B) |
| gnomAD constraint |
pLI=0.16, LOEUF=0.624 — LoF-tolerant |
| GWAS Catalog |
36 unique SNPs / 72 rows |
| ClinVar |
116 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
4 clinical annotations across 3 drugs |
phenome — Top 30 of 939 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘TNFRSF1B’ and resolved to ‘Tumor necrosis factor receptor superfamily member 1B’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 116 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 19 of 19 traits by best p-value, aggregated from 30 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/P20333 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000028137/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL1250356/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/TNFRSF1B — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/TNFRSF1B — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=TNFRSF1B%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=TNFRSF1B — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/TNFRSF1B — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:26:31 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none