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 |
| Height |
0.0149 |
0.00373 |
6.33e-05 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
0.00979 |
0.00263 |
2.01e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: arthritis (nos) |
-0.15 |
0.0407 |
2.21e-04 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: G56 Mononeuropathies of upper limb |
0.0747 |
0.0215 |
4.99e-04 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
0.00699 |
0.0025 |
0.00507 |
Wald ratio |
1 |
cis |
NA |
| Body fat |
-0.0157 |
0.0069 |
0.0232 |
Wald ratio |
1 |
cis |
NA |
| Schizophrenia |
-0.0295 |
0.0136 |
0.0299 |
Wald ratio |
1 |
cis |
NA |
| Cigarettes smoked per day |
0.221 |
0.104 |
0.0336 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: pernicious anaemia |
-0.137 |
0.0645 |
0.0342 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: basal cell carcinoma |
0.0621 |
0.0298 |
0.0373 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: diverticular disease or diverticulitis |
0.0559 |
0.0272 |
0.0398 |
Wald ratio |
1 |
cis |
NA |
| Potassium in urine |
-0.00614 |
0.00309 |
0.0465 |
Wald ratio |
1 |
cis |
NA |
| …and 104 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3168_8_2 |
ADAMTS-5 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
80 association rows across 41 traits (74 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 |
| A disintegrin and metalloproteinase with thrombospondin moti |
4e-469 |
rs2830586 |
10 |
GCST90246431 |
no MR -> candidate analysis |
| Blood protein levels |
1e-249 |
rs2830585 |
1 |
GCST006585 |
no MR -> candidate analysis |
| TGFBR3 protein levels |
1e-135 |
rs1236213 |
7 |
GCST90470848 |
no MR -> candidate analysis |
| Circulating TGFBR3 levels |
1e-127 |
rs1236213 |
5 |
GCST90860476 |
no MR -> candidate analysis |
| HYOU1/TGFBR3 protein level ratio |
3e-101 |
rs406835 |
1 |
GCST90315105 |
no MR -> candidate analysis |
| Height |
5e-92 |
rs2830586 |
15 |
GCST90245848 |
MR: beta=0.0149, p=6.33e-05 (cis) |
| A disintegrin and metalloproteinase with thrombospondin moti |
2e-72 |
rs2830586 |
2 |
GCST90240165 |
no MR -> candidate analysis |
| Transforming growth factor beta receptor type 3 levels |
3e-20 |
rs1034350 |
1 |
GCST90249855 |
no MR -> candidate analysis |
| Standing height (UKB data field 50) |
5e-18 |
rs2830581 |
1 |
GCST90468178 |
no MR -> candidate analysis |
| TNXB protein levels |
6e-17 |
rs1236213 |
1 |
GCST90470930 |
no MR -> candidate analysis |
| Circulating TNXB levels |
2e-16 |
rs1236213 |
1 |
GCST90860458 |
no MR -> candidate analysis |
| Height (baseline) |
3e-13 |
rs2830581 |
1 |
GCST90565843 |
no MR -> candidate analysis |
| …and 29 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 366 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 |
| Abnormality of the skeletal system |
0.883 |
— |
common-variant locus |
no MR -> candidate analysis |
| major depressive disorder |
0.71 |
— |
common-variant locus |
no MR -> candidate analysis |
| synovium disorder |
0.579 |
— |
common-variant locus |
no MR -> candidate analysis |
| information processing speed |
0.521 |
— |
common-variant locus |
no MR -> candidate analysis |
| alcohol drinking |
0.516 |
— |
common-variant locus |
no MR -> candidate analysis |
| pelvic organ prolapse |
0.463 |
— |
common-variant locus |
no MR -> candidate analysis |
| glioblastoma |
0.43 |
— |
common-variant locus |
no MR -> candidate analysis |
| pyogenic granuloma |
0.44 |
— |
common-variant locus |
no MR -> candidate analysis |
| colorectal carcinoma |
0.396 |
— |
common-variant locus |
no MR -> candidate analysis |
| urolithiasis |
0.419 |
— |
common-variant locus |
no MR -> candidate analysis |
| stroke disorder |
0.388 |
— |
common-variant locus |
no MR -> candidate analysis |
| eye disorder |
0.367 |
— |
common-variant locus |
no MR -> candidate analysis |
| Umbilical hernia |
0.364 |
— |
common-variant locus |
no MR -> candidate analysis |
| Dupuytren Contracture |
0.364 |
— |
common-variant locus |
no MR -> candidate analysis |
| ventral hernia |
0.364 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 15 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 (A disintegrin and metalloproteinase with thrombospondin motifs 5) |
| gnomAD constraint |
pLI=3.9e-12, LOEUF=0.832 — LoF-tolerant |
| GWAS Catalog |
51 unique SNPs / 96 rows |
| ClinVar |
236 records; 4 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 366 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 ‘ADAMTS5’ and resolved to ‘A disintegrin and metalloproteinase with thrombospondin motifs 5’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 236 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 41 traits by best p-value, aggregated from 80 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/Q9UNA0 — 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/ENSG00000154736/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2285/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/ADAMTS5 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/ADAMTS5 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=ADAMTS5%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/ADAMTS5 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T00:54:38 · 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