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 |
| Mean platelet volume |
-0.0813 |
0.0047 |
4.12e-67 |
Wald ratio |
1 |
trans |
NA |
| Platelet count |
26 |
1.73 |
5.20e-51 |
Wald ratio |
1 |
trans |
NA |
| Systemic lupus erythematosus |
0.502 |
0.171 |
0.00333 |
Wald ratio |
1 |
trans |
NA |
| Juvenile idiopathic arthritis |
0.511 |
0.201 |
0.0108 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: hypertension |
0.037 |
0.0146 |
0.0111 |
Wald ratio |
1 |
trans |
NA |
| Years of schooling |
-0.0325 |
0.0145 |
0.0244 |
Wald ratio |
1 |
trans |
NA |
| Knee and hip osteoarthritis |
0.176 |
0.0795 |
0.0265 |
Wald ratio |
1 |
trans |
NA |
| Schizophrenia |
-0.0875 |
0.0398 |
0.0278 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation |
0.12 |
0.0549 |
0.0295 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: I48 Atrial fibrillation and flutter |
0.157 |
0.0721 |
0.0298 |
Wald ratio |
1 |
trans |
NA |
| 2hr glucose |
0.166 |
0.0795 |
0.0365 |
Wald ratio |
1 |
trans |
NA |
| Squamous cell lung cancer |
0.202 |
0.0978 |
0.0385 |
Wald ratio |
1 |
trans |
NA |
| …and 96 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3170_6_1 |
AMPM2 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
18 association rows across 16 traits (16 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 |
| Height |
7e-65 |
rs2596741 |
2 |
GCST90245848 |
no MR -> candidate analysis |
| High light scatter reticulocyte percentage of red cells |
3e-53 |
rs784487 |
1 |
GCST90002386 |
no MR -> candidate analysis |
| High light scatter reticulocyte count |
1e-51 |
rs784487 |
1 |
GCST90002385 |
no MR -> candidate analysis |
| Immature fraction of reticulocytes |
1e-45 |
rs34994986 |
2 |
GCST90002387 |
no MR -> candidate analysis |
| Reticulocyte count |
3e-32 |
rs784487 |
1 |
GCST90002405 |
no MR -> candidate analysis |
| height (mean, inv-normal transformed) |
9e-17 |
rs301033 |
1 |
GCST90479635 |
no MR -> candidate analysis |
| Height (maximum, inv-normal transformed) |
6e-16 |
rs301033 |
1 |
GCST90479634 |
no MR -> candidate analysis |
| Circulating METAP2 levels |
8e-16 |
rs784487 |
1 |
GCST90860036 |
no MR -> candidate analysis |
| METAP2 protein levels |
1e-14 |
rs784487 |
1 |
GCST90469894 |
no MR -> candidate analysis |
| Core binding factor acute myeloid leukemia |
2e-10 |
rs301009; rs301011; rs11614671; rs4762519; rs11519597; rs2769469; rs2596741; rs3794261; rs1057739; rs301026; rs301024; rs7974458; rs301003; rs10777699; rs3812813; rs11108094; rs10498964; rs2769444 |
1 |
GCST008413 |
no MR -> candidate analysis |
| Sex hormone-binding globulin levels |
8e-10 |
rs528806375 |
1 |
GCST90012107 |
no MR -> candidate analysis |
| Sex hormone-binding globulin levels adjusted for BMI |
2e-9 |
rs528806375 |
1 |
GCST90012106 |
no MR -> candidate analysis |
| …and 4 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 166 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 |
| preeclampsia |
0.441 |
— |
common-variant locus |
no MR -> candidate analysis |
| type 2 diabetes mellitus |
0.266 |
— |
common-variant locus |
no MR -> candidate analysis |
| sialolithiasis |
0.142 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 3 rows above, 3 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 (Methionine aminopeptidase 2) |
| gnomAD constraint |
pLI=0.16, LOEUF=0.588 — LoF-tolerant |
| GWAS Catalog |
70 unique SNPs / 140 rows |
| ClinVar |
63 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 166 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 ‘METAP2’ and resolved to ‘Methionine aminopeptidase 2’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 63 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 16 of 16 traits by best p-value, aggregated from 18 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/P50579 — 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/ENSG00000111142/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3922/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/METAP2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/METAP2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=METAP2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/METAP2 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:46:17 · 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