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 |
| Eczema |
0.132 |
0.0348 |
1.52e-04 |
Wald ratio |
1 |
cis |
NA |
| Ischemic stroke |
-0.107 |
0.0321 |
8.14e-04 |
Wald ratio |
1 |
cis |
NA |
| Large vessel disease |
-0.217 |
0.0657 |
9.84e-04 |
Wald ratio |
1 |
cis |
NA |
| Coronary heart disease |
-0.0599 |
0.0188 |
0.00143 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: psoriasis |
0.116 |
0.0392 |
0.00297 |
Wald ratio |
1 |
cis |
NA |
| Myocardial infarction |
-0.0611 |
0.0207 |
0.00319 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R07 Pain in throat and chest |
-0.0653 |
0.0222 |
0.00331 |
Wald ratio |
1 |
cis |
NA |
| Sodium in urine |
0.0121 |
0.0046 |
0.00863 |
Wald ratio |
1 |
cis |
NA |
| Amyotrophic lateral sclerosis |
0.0707 |
0.0335 |
0.0348 |
Wald ratio |
1 |
cis |
NA |
| Clear cell ovarian cancer |
0.165 |
0.0797 |
0.0382 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: anxiety or panic attacks |
-0.0882 |
0.044 |
0.0451 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt |
-0.115 |
0.0583 |
0.0479 |
Wald ratio |
1 |
cis |
NA |
| …and 89 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4496_60_2 |
MMP-12 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
116 association rows across 27 traits (58 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 MMP12 levels (id: OID00456_OID21439) |
7e-2537 |
rs17368814 |
2 |
GCST90859817 |
no MR -> candidate analysis |
| Circulating MMP12 levels (id: OID00829_OID21439) |
2e-1530 |
rs17368814 |
2 |
GCST90860157 |
no MR -> candidate analysis |
| Matrix metalloproteinase-12 levels |
1e-951 |
rs72981675 |
2 |
GCST90012070 |
no MR -> candidate analysis |
| Matrix metalloproteinase-3 levels |
7e-822 |
rs632478 |
2 |
GCST90012027 |
no MR -> candidate analysis |
| Macrophage metalloelastase levels |
2e-289 |
rs17368814 |
7 |
GCST90248497 |
no MR -> candidate analysis |
| Blood protein levels in cardiovascular risk |
3e-171 |
rs17368659 |
1 |
GCST009731 |
no MR -> candidate analysis |
| Serum levels of protein MMP12 |
1e-127 |
rs2276109 |
1 |
GCST90088718 |
no MR -> candidate analysis |
| Macrophage metalloelastase levels (MMP12.4496.60.2) |
5e-111 |
rs28381684 |
1 |
GCST90241856 |
no MR -> candidate analysis |
| MMP12 protein levels |
2e-77 |
rs662028 |
1 |
GCST90469916 |
no MR -> candidate analysis |
| Blood protein levels |
5e-77 |
rs17368582 |
2 |
GCST006585 |
no MR -> candidate analysis |
| Cerebrospinal fluid levels of Alzheimer’s disease-related pr |
2e-44 |
rs573521 |
1 |
GCST002665 |
no MR -> candidate analysis |
| MMP3 protein levels |
6e-35 |
rs78406549 |
5 |
GCST90469920 |
no MR -> candidate analysis |
| …and 15 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 639 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 |
| atopic eczema |
0.735 |
— |
common-variant locus |
no MR -> candidate analysis |
| stroke disorder |
0.662 |
— |
common-variant locus |
no MR -> candidate analysis |
| peripheral vascular disease |
0.673 |
— |
common-variant locus |
no MR -> candidate analysis |
| ischemic stroke |
0.628 |
— |
common-variant locus |
MR: beta=-0.107, p=8.14e-04 (cis) |
| atherosclerosis |
0.619 |
— |
common-variant locus |
no MR -> candidate analysis |
| aneurysm |
0.517 |
— |
common-variant locus |
no MR -> candidate analysis |
| abdominal aortic aneurysm |
0.516 |
— |
common-variant locus |
no MR -> candidate analysis |
| aortic aneurysm |
0.517 |
— |
common-variant locus |
no MR -> candidate analysis |
| Cerebral ischemia |
0.478 |
— |
common-variant locus |
no MR -> candidate analysis |
| coronary artery disorder |
0.439 |
— |
common-variant locus |
no MR -> candidate analysis |
| cerebrovascular disorder |
0.414 |
— |
common-variant locus |
no MR -> candidate analysis |
| occlusion precerebral artery |
0.41 |
— |
common-variant locus |
no MR -> candidate analysis |
| tooth disorder |
0.293 |
— |
common-variant locus |
no MR -> candidate analysis |
| chronic obstructive pulmonary disease |
0.104 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 14 rows above, 13 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 |
3 known modulators (Macrophage metalloelastase) |
| gnomAD constraint |
pLI=9.1e-20, LOEUF=1.42 — LoF-tolerant |
| GWAS Catalog |
169 unique SNPs / 406 rows |
| ClinVar |
66 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 639 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 ‘MMP12’ and resolved to ‘Macrophage metalloelastase’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 66 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 27 traits by best p-value, aggregated from 116 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/P39900 — 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/ENSG00000262406/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4393/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/MMP12 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/MMP12 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=MMP12%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/MMP12 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:50:07 · 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