Protein Dossier — TNFRSF11A (Tumor necrosis factor receptor superfamily member 11A)
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 |
| Paget’s disease |
2.15 |
0.297 |
4.72e-13 |
Wald ratio |
1 |
cis |
0.99 |
| Heel bone mineral density (BMD) T-score automated |
-0.111 |
0.0161 |
6.61e-12 |
Wald ratio |
1 |
cis |
1 |
| Lumbar spine bone mineral density |
-0.278 |
0.0457 |
1.12e-09 |
Wald ratio |
1 |
cis |
NA |
| Femoral neck bone mineral density |
-0.189 |
0.0394 |
1.60e-06 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: osteoporosis |
0.27 |
0.0767 |
4.31e-04 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Wrist |
0.229 |
0.071 |
0.00127 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] |
-0.472 |
0.148 |
0.00138 |
Wald ratio |
1 |
cis |
NA |
| Body mass index (BMI) |
-0.0362 |
0.0124 |
0.00361 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse |
0.349 |
0.121 |
0.00393 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
0.0279 |
0.0102 |
0.00621 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] |
-0.375 |
0.155 |
0.0158 |
Wald ratio |
1 |
cis |
NA |
| Fasting insulin |
-0.0371 |
0.0161 |
0.0211 |
Wald ratio |
1 |
cis |
NA |
| …and 104 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5424_55_3 |
RANK |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
120 association rows across 71 traits (109 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 |
| TNFRSF11A/TNFRSF1A protein level ratio |
1e-1835 |
rs74938001 |
1 |
GCST90315928 |
no MR -> candidate analysis |
| Circulating TNFRSF11A levels |
2e-1622 |
rs62098352 |
3 |
GCST90859756 |
no MR -> candidate analysis |
| TNFRSF11A/TNFRSF1B protein level ratio |
2e-1447 |
rs74938001 |
1 |
GCST90315929 |
no MR -> candidate analysis |
| Tumor necrosis factor receptor superfamily member 11A levels |
9e-101 |
rs80067526 |
3 |
GCST90179450 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein TNFRSF11A levels |
2e-79 |
rs35211496 |
1 |
GCST90943993 |
no MR -> candidate analysis |
| Alkaline phosphatase (UKB data field 30610) |
3e-73 |
rs884205 |
1 |
GCST90468060 |
no MR -> candidate analysis |
| Serum alkaline phosphatase levels |
3e-65 |
rs884205 |
7 |
GCST90018942 |
no MR -> candidate analysis |
| TNFRSF11A protein levels |
9e-47 |
rs141434942 |
10 |
GCST90470902 |
no MR -> candidate analysis |
| Heel bone mineral density |
6e-38 |
rs884205 |
7 |
GCST006979 |
MR: beta=-0.111, p=6.61e-12 (cis) |
| Estimated bone mineral density |
3e-35 |
rs884205 |
2 |
GCST90726625 |
no MR -> candidate analysis |
| Height |
5e-28 |
rs884205 |
2 |
GCST90245848 |
MR: beta=0.0183, p=0.228 (cis) |
| Circulating COL1A1 levels |
4e-27 |
rs2957126 |
1 |
GCST90859986 |
no MR -> candidate analysis |
| …and 59 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 1431 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 |
| Osteopetrosis - hypogammaglobulinemia |
0.847 |
— |
established (curated) |
no MR -> candidate analysis |
| autosomal recessive osteopetrosis 7 |
0.829 |
— |
established (curated) |
no MR -> candidate analysis |
| familial expansile osteolysis |
0.738 |
— |
established (curated) |
no MR -> candidate analysis |
| bone Paget disease |
0.531 |
— |
established (curated) |
no MR -> candidate analysis |
| osteoporosis |
0.839 |
— |
common-variant locus |
MR: beta=0.27, p=4.31e-04 (cis) |
| bone disorder |
0.582 |
— |
established (curated) |
MR: beta=0.177, p=0.458 (cis) |
| asthma |
0.69 |
— |
common-variant locus |
no MR -> candidate analysis |
| hypothyroidism |
0.715 |
— |
common-variant locus |
MR: beta=-0.143, p=0.0261 (cis) |
| allergic rhinitis |
0.696 |
— |
common-variant locus |
MR: beta=-0.0945, p=0.0941 (cis) |
| Eczematoid dermatitis |
0.664 |
— |
common-variant locus |
no MR -> candidate analysis |
| childhood onset asthma |
0.656 |
— |
common-variant locus |
no MR -> candidate analysis |
| myasthenia gravis |
0.629 |
— |
common-variant locus |
no MR -> candidate analysis |
| dysosteosclerosis |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| osteoarthritis, hip |
0.609 |
— |
common-variant locus |
MR: beta=-0.183, p=0.0864 (cis) |
| myxedema |
0.604 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 10 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 ligand superfamily member 11/11A) |
| gnomAD constraint |
pLI=5.4e-06, LOEUF=0.772 — LoF-tolerant |
| GWAS Catalog |
73 unique SNPs / 146 rows |
| ClinVar |
891 records; 5 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
2 clinical annotations across 6 drugs |
phenome — Top 30 of 1431 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 ‘TNFRSF11A’ and resolved to ‘Tumor necrosis factor ligand superfamily member 11/11A’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 891 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 71 traits by best p-value, aggregated from 120 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/Q9Y6Q6 — 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/ENSG00000141655/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4296079/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/TNFRSF11A — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/TNFRSF11A — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=TNFRSF11A%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=TNFRSF11A — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/TNFRSF11A — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:25:58 · 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