Protein Dossier — TNFSF14 (Tumor necrosis factor ligand superfamily member 14)
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 |
| Cancer code self-reported: prostate cancer |
-0.3 |
0.113 |
0.008 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema |
-0.0879 |
0.0343 |
0.0103 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.0556 |
0.0227 |
0.0142 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: ankylosing spondylitis |
0.254 |
0.105 |
0.0152 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R10 Abdominal and pelvic pain |
-0.0863 |
0.0372 |
0.0203 |
Wald ratio |
1 |
cis |
NA |
| Cardioembolic stroke |
-0.18 |
0.088 |
0.0411 |
Wald ratio |
1 |
cis |
NA |
| Small vessel disease |
-0.202 |
0.101 |
0.0466 |
Wald ratio |
1 |
cis |
NA |
| Transferrin |
0.0697 |
0.0364 |
0.0554 |
Wald ratio |
1 |
cis |
NA |
| Sodium in urine |
0.0133 |
0.00694 |
0.0557 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I83 Varicose veins of lower extremities |
0.085 |
0.0453 |
0.0609 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: L03 Cellulitis |
0.13 |
0.0693 |
0.0615 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K40 Inguinal hernia |
0.0743 |
0.0401 |
0.0638 |
Wald ratio |
1 |
cis |
NA |
| …and 83 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5355_69_3 |
LIGHT |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
102 association rows across 46 traits (97 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 TNFSF14 levels (id: OID00506_OID20953) |
8e-534 |
rs344560 |
5 |
GCST90859862 |
no MR -> candidate analysis |
| HGF/TNFSF14 protein level ratio |
1e-413 |
rs344560 |
1 |
GCST90315060 |
no MR -> candidate analysis |
| TNFRSF14/TNFSF14 protein level ratio |
3e-369 |
rs344560 |
1 |
GCST90315936 |
no MR -> candidate analysis |
| CD40LG/TNFSF14 protein level ratio |
1e-360 |
rs344560 |
1 |
GCST90313827 |
no MR -> candidate analysis |
| Circulating TNFSF14 levels (id: OID00787_OID20953) |
6e-333 |
rs344560 |
5 |
GCST90860119 |
no MR -> candidate analysis |
| CD70 protein levels |
8e-214 |
rs80196597 |
16 |
GCST90468645 |
no MR -> candidate analysis |
| TNFSF14 protein levels |
6e-208 |
rs413141 |
5 |
GCST90470922 |
no MR -> candidate analysis |
| Tumor necrosis factor ligand superfamily member 14 levels |
8e-173 |
rs344560 |
7 |
GCST90012029 |
no MR -> candidate analysis |
| FUT8/TNFSF14 protein level ratio |
5e-79 |
rs1077667 |
1 |
GCST90314895 |
no MR -> candidate analysis |
| Monocyte count |
8e-58 |
rs413141 |
8 |
GCST90002344 |
no MR -> candidate analysis |
| LTA protein levels |
1e-50 |
rs344560 |
1 |
GCST90469813 |
no MR -> candidate analysis |
| Circulating LTA levels |
2e-48 |
rs344560 |
1 |
GCST90859910 |
no MR -> candidate analysis |
| …and 34 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 702 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 |
| multiple sclerosis |
0.773 |
— |
common-variant locus |
no MR -> candidate analysis |
| thyroid gland disorder |
0.56 |
— |
common-variant locus |
no MR -> candidate analysis |
| hypothyroidism |
0.493 |
— |
common-variant locus |
MR: beta=-0.0879, p=0.0103 (cis) |
| colorectal carcinoma |
0.285 |
— |
common-variant locus |
no MR -> candidate analysis |
| malunion fracture |
0.293 |
— |
common-variant locus |
no MR -> candidate analysis |
| gestational diabetes |
0.293 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 6 rows above, 5 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 |
2 known modulators (Tumor necrosis factor ligand superfamily member 14) |
| gnomAD constraint |
pLI=0.00042, LOEUF=1.02 — LoF-tolerant |
| GWAS Catalog |
102 unique SNPs / 216 rows |
| ClinVar |
54 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 702 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 ‘TNFSF14’ and resolved to ‘Tumor necrosis factor ligand superfamily member 14’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 54 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 46 traits by best p-value, aggregated from 102 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/O43557 — 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/ENSG00000125735/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3712914/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/TNFSF14 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/TNFSF14 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=TNFSF14%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/TNFSF14 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:27:42 · 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