Protein Dossier — ADAM12 (Disintegrin and metalloproteinase domain-containing protein 12)
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 |
| Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level |
0.854 |
0.258 |
9.42e-04 |
Wald ratio |
1 |
cis |
NA |
| Height |
0.0464 |
0.0148 |
0.00175 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypertension |
-0.0656 |
0.0215 |
0.00228 |
Wald ratio |
1 |
cis |
NA |
| Mean cell haemoglobin |
0.153 |
0.0517 |
0.00305 |
Wald ratio |
1 |
cis |
NA |
| Schizophrenia |
-0.15 |
0.0517 |
0.00376 |
Wald ratio |
1 |
cis |
NA |
| Body mass index (BMI) |
-0.0315 |
0.0118 |
0.00765 |
Wald ratio |
1 |
cis |
NA |
| Red blood cell count |
-0.0292 |
0.0115 |
0.011 |
Wald ratio |
1 |
cis |
NA |
| Endometrioid ovarian cancer |
0.345 |
0.147 |
0.0194 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
-0.038 |
0.0175 |
0.0293 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: high cholesterol |
-0.071 |
0.0343 |
0.0386 |
Wald ratio |
1 |
cis |
NA |
| Years of schooling |
0.0383 |
0.0191 |
0.0455 |
Wald ratio |
1 |
cis |
NA |
| Mean cell volume |
0.263 |
0.133 |
0.0487 |
Wald ratio |
1 |
cis |
NA |
| …and 81 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4420_7_2 |
ADAM12 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
83 association rows across 59 traits (48 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 |
| ADAM12 protein levels |
8e-74 |
rs11244909 |
3 |
GCST90468216 |
no MR -> candidate analysis |
| Height |
6e-73 |
rs7920091 |
17 |
GCST90245848 |
MR: beta=0.0464, p=0.00175 (cis) |
| Disintegrin and metalloproteinase domain-containing protein |
4e-38 |
rs11244958 |
1 |
GCST90426031 |
no MR -> candidate analysis |
| Hematological and neurological expressed 1 protein levels |
9e-22 |
rs10901598 |
1 |
GCST90423531 |
no MR -> candidate analysis |
| Blood protein levels |
1e-16 |
rs10794057 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Estimated bone mineral density |
2e-15 |
rs7090615 |
1 |
GCST90726625 |
no MR -> candidate analysis |
| Heel bone mineral density |
5e-14 |
rs11244909 |
3 |
GCST006433 |
MR: beta=-0.0223, p=0.143 (cis) |
| Body shape phenotype PC2 |
2e-12 |
rs1674896 |
1 |
GCST90832990 |
no MR -> candidate analysis |
| Cortical surface area |
7e-12 |
rs1278250 |
1 |
GCST90091060 |
no MR -> candidate analysis |
| Balanoposthitis (PheCode 601.4) |
2e-11 |
rs916351393 |
1 |
GCST90480410 |
no MR -> candidate analysis |
| Total PHF-tau (SNP x SNP interaction) |
3e-11 |
rs1385292 x rs7084896 |
1 |
GCST010340 |
no MR -> candidate analysis |
| Sialoadenitis (PheCode 527.2) |
4e-11 |
rs186288708 |
1 |
GCST90480283 |
no MR -> candidate analysis |
| …and 47 more traits (see JSON) |
|
|
|
|
|
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 345 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 |
| intelligence |
0.524 |
— |
common-variant locus |
no MR -> candidate analysis |
| spermatocele |
0.523 |
— |
common-variant locus |
no MR -> candidate analysis |
| balanoposthitis |
0.523 |
— |
common-variant locus |
no MR -> candidate analysis |
| open-angle glaucoma |
0.521 |
— |
common-variant locus |
no MR -> candidate analysis |
| COVID-19 |
0.483 |
— |
common-variant locus |
no MR -> candidate analysis |
| depressive disorder |
0.485 |
— |
common-variant locus |
no MR -> candidate analysis |
| placenta praevia |
0.485 |
— |
common-variant locus |
no MR -> candidate analysis |
| corneal neovascularization |
0.485 |
— |
common-variant locus |
no MR -> candidate analysis |
| sialadenitis |
0.485 |
— |
common-variant locus |
no MR -> candidate analysis |
| spinal cord injury |
0.482 |
— |
common-variant locus |
no MR -> candidate analysis |
| facial morphology |
0.479 |
— |
common-variant locus |
no MR -> candidate analysis |
| dislocation |
0.472 |
— |
common-variant locus |
no MR -> candidate analysis |
| inherited hemoglobinopathy |
0.33 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of limbs |
0.316 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the immune system |
0.299 |
— |
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 |
0 known modulators (Disintegrin and metalloproteinase domain-containing protein 12) |
| gnomAD constraint |
pLI=2.9e-15, LOEUF=0.803 — LoF-tolerant |
| GWAS Catalog |
120 unique SNPs / 290 rows |
| ClinVar |
221 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 345 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 ‘ADAM12’ and resolved to ‘Disintegrin and metalloproteinase domain-containing protein 12’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 221 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 59 traits by best p-value, aggregated from 83 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/O43184 — 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/ENSG00000148848/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL5030/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/ADAM12 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/ADAM12 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=ADAM12%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/ADAM12 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T00:52:50 · 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