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 |
| Myocardial infarction |
-0.0389 |
0.0119 |
0.00111 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: anxiety or panic attacks |
0.0752 |
0.0231 |
0.00114 |
Wald ratio |
1 |
cis |
NA |
| Coronary heart disease |
-0.0328 |
0.0108 |
0.00234 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: B37 Candidiasis |
0.311 |
0.102 |
0.00236 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: malignant melanoma |
0.0781 |
0.0303 |
0.0101 |
Wald ratio |
1 |
cis |
NA |
| Urate |
0.0161 |
0.00645 |
0.0124 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: muscle or soft tissue injuries |
0.0746 |
0.0317 |
0.0186 |
Wald ratio |
1 |
cis |
NA |
| Subjective well being |
0.00967 |
0.0043 |
0.0244 |
Wald ratio |
1 |
cis |
NA |
| Internalizing problems |
-0.059 |
0.0269 |
0.0281 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: deep venous thrombosis (dvt) |
0.043 |
0.0196 |
0.0285 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: mania or bipolar disorder or manic depression |
0.111 |
0.0508 |
0.0292 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: arthritis (nos) |
0.0677 |
0.0311 |
0.0295 |
Wald ratio |
1 |
cis |
NA |
| …and 98 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2480_58_3 |
TIMP-3 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
12 association rows across 6 traits (11 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 |
| TIMP3 protein levels |
4e-68 |
rs116959820 |
2 |
GCST90470871 |
no MR -> candidate analysis |
| Metalloproteinase inhibitor 3 levels |
2e-20 |
rs242069 |
4 |
GCST90161365 |
no MR -> candidate analysis |
| Free Cholesterol to Cholesteryl Esters in Large HDL ratio |
4e-15 |
rs117004633 |
1 |
GCST90827800 |
no MR -> candidate analysis |
| acne vulgaris |
1e-10 |
rs135025 |
3 |
GCST90092000 |
no MR -> candidate analysis |
| Depression x environmental factor score interaction |
4e-8 |
rs536631793 |
1 |
GCST90102448 |
no MR -> candidate analysis |
| Triglyceride levels |
2e-7 |
rs1065314 |
1 |
GCST008150 |
no MR -> candidate analysis |
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 1907 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 |
| Sorsby fundus dystrophy |
0.859 |
— |
established (curated) |
no MR -> candidate analysis |
| Sorsby’s fundus dystrophy |
0.489 |
— |
established (curated) |
no MR -> candidate analysis |
| Retinal dystrophy |
0.851 |
— |
established (curated) |
no MR -> candidate analysis |
| venous thromboembolism |
0.705 |
— |
common-variant locus |
no MR -> candidate analysis |
| open-angle glaucoma |
0.685 |
— |
common-variant locus |
no MR -> candidate analysis |
| glaucoma |
0.677 |
— |
common-variant locus |
MR: beta=-0.0495, p=0.0501 (cis) |
| retinal disorder |
0.669 |
— |
established (curated) |
no MR -> candidate analysis |
| acne |
0.667 |
— |
common-variant locus |
no MR -> candidate analysis |
| cutaneous lupus erythematosus |
0.484 |
— |
common-variant locus |
no MR -> candidate analysis |
| Cerebral arteriovenous malformation |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| stricture |
0.391 |
— |
common-variant locus |
no MR -> candidate analysis |
| ductal breast carcinoma in situ |
0.344 |
— |
common-variant locus |
no MR -> candidate analysis |
| age-related macular degeneration |
0.259 |
— |
common-variant locus |
no MR -> candidate analysis |
| obesity disorder |
0.267 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.259 |
— |
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 |
0 known modulators (Metalloproteinase inhibitor 3) |
| gnomAD constraint |
pLI=0.7, LOEUF=0.606 — LoF-tolerant |
| GWAS Catalog |
110 unique SNPs / 254 rows |
| ClinVar |
302 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1907 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 ‘TIMP3’ and resolved to ‘Metalloproteinase inhibitor 3’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 302 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 6 of 6 traits by best p-value, aggregated from 12 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/P35625 — 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/ENSG00000100234/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL5465289/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/TIMP3 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/TIMP3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=TIMP3%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/TIMP3 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:21:54 · 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