Protein Dossier — TNFSF11 (Tumor necrosis factor ligand superfamily member 11)
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 |
| Iron |
-0.122 |
0.045 |
0.00679 |
Wald ratio |
1 |
trans |
NA |
| Autism |
0.337 |
0.129 |
0.009 |
Wald ratio |
1 |
trans |
NA |
| Urinary albumin-to-creatinine ratio |
0.0545 |
0.0268 |
0.042 |
Wald ratio |
1 |
trans |
NA |
| Ferritin |
-0.085 |
0.0423 |
0.0444 |
Wald ratio |
1 |
trans |
NA |
| Hirschsprung’s disease |
1.23 |
0.616 |
0.0455 |
Wald ratio |
1 |
trans |
NA |
| Intracranial volume |
1.26e+04 |
6.44e+03 |
0.0504 |
Wald ratio |
1 |
trans |
NA |
| Ischemic stroke |
0.143 |
0.0755 |
0.0585 |
Wald ratio |
1 |
trans |
NA |
| Age at menarche |
0.0455 |
0.0251 |
0.07 |
Wald ratio |
1 |
trans |
NA |
| Chronic kidney disease |
0.123 |
0.0682 |
0.0719 |
Wald ratio |
1 |
trans |
NA |
| Transferrin Saturation |
-0.0809 |
0.045 |
0.0722 |
Wald ratio |
1 |
trans |
NA |
| Bulimia nervosa |
0.0545 |
0.0318 |
0.0865 |
Wald ratio |
1 |
trans |
NA |
| Subjective well being |
0.0227 |
0.0136 |
0.0956 |
Wald ratio |
1 |
trans |
NA |
| …and 30 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2917_3_2 |
sRANKL |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
87 association rows across 56 traits (76 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 |
| Alkaline phosphatase (UKB data field 30610) |
1e-45 |
rs665632 |
2 |
GCST90468060 |
no MR -> candidate analysis |
| Circulating SOST levels |
3e-31 |
rs138818878 |
5 |
GCST90860381 |
no MR -> candidate analysis |
| Estimated bone mineral density |
5e-28 |
rs117543324 |
2 |
GCST90726625 |
no MR -> candidate analysis |
| Serum alkaline phosphatase levels |
5e-26 |
rs9533177 |
5 |
GCST90018722 |
no MR -> candidate analysis |
| Heel bone mineral density |
1e-24 |
rs138818878 |
6 |
GCST007066 |
no MR -> candidate analysis |
| Eosinophill percentage (UKB data field 30210) |
1e-23 |
rs9525630 |
1 |
GCST90468069 |
no MR -> candidate analysis |
| DXA-Bone mineral density (lumbar spine) |
5e-23 |
rs78667121 |
1 |
GCST90568448 |
no MR -> candidate analysis |
| DXA-Bone mineral density (spine) (UKB data field 23234) |
5e-23 |
rs78667121 |
1 |
GCST90568454 |
no MR -> candidate analysis |
| SOST protein levels |
6e-23 |
rs138818878 |
3 |
GCST90470711 |
no MR -> candidate analysis |
| Serum sclerostin levels |
6e-23 |
rs34136735 |
2 |
GCST90320249 |
no MR -> candidate analysis |
| DXA-Bone mineral density (trunk) (UKB data field 23241) |
2e-20 |
rs78667121 |
1 |
GCST90568456 |
no MR -> candidate analysis |
| Total body bone mineral density |
1e-19 |
rs116926994 |
5 |
GCST005348 |
no MR -> candidate analysis |
| …and 44 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 2890 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 |
| osteoporosis |
0.759 |
— |
common-variant locus |
no MR -> candidate analysis |
| autosomal recessive osteopetrosis 2 |
0.84 |
— |
established (curated) |
no MR -> candidate analysis |
| Autosomal recessive malignant osteopetrosis |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| bone disorder |
0.499 |
— |
established (curated) |
no MR -> candidate analysis |
| hypothyroidism |
0.839 |
— |
common-variant locus |
no MR -> candidate analysis |
| osteoarthritis, knee |
0.728 |
— |
common-variant locus |
no MR -> candidate analysis |
| myxedema |
0.685 |
— |
common-variant locus |
no MR -> candidate analysis |
| lichen planus |
0.658 |
— |
common-variant locus |
no MR -> candidate analysis |
| Crohn disease |
0.626 |
— |
common-variant locus |
no MR -> candidate analysis |
| primary biliary cholangitis |
0.618 |
— |
common-variant locus |
no MR -> candidate analysis |
| Nasal polyposis |
0.642 |
— |
common-variant locus |
no MR -> candidate analysis |
| skeletal system disorder |
0.649 |
— |
common-variant locus |
no MR -> candidate analysis |
| autoimmune thyroid disease |
0.644 |
— |
common-variant locus |
no MR -> candidate analysis |
| rheumatoid arthritis |
0.51 |
— |
common-variant locus |
MR: beta=-0.09, p=0.256 (trans) |
| juvenile idiopathic arthritis |
0.551 |
— |
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 |
1 known modulators (Tumor necrosis factor ligand superfamily member 11) |
| gnomAD constraint |
pLI=0.66, LOEUF=0.604 — LoF-tolerant |
| GWAS Catalog |
106 unique SNPs / 177 rows |
| ClinVar |
323 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
1 clinical annotations across 2 drugs |
phenome — Top 30 of 2890 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 ‘TNFSF11’ and resolved to ‘Tumor necrosis factor ligand superfamily member 11’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 323 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 56 traits by best p-value, aggregated from 87 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/O14788 — 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/ENSG00000120659/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2364162/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/TNFSF11 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/TNFSF11 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=TNFSF11%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=TNFSF11 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/TNFSF11 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:27:06 · 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