Protein Dossier — MAP2K2 (Dual specificity mitogen-activated protein kinase kinase 2)
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 |
| Diastolic blood pressure automated reading |
-0.0168 |
0.00521 |
0.00131 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: asthma |
0.0406 |
0.0137 |
0.00299 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: depression |
0.0545 |
0.0199 |
0.00611 |
Wald ratio |
1 |
trans |
NA |
| Sleep duration |
0.0108 |
0.00397 |
0.00665 |
Wald ratio |
1 |
trans |
NA |
| Hearing difficulty or problems: Yes |
0.0221 |
0.0086 |
0.0102 |
Wald ratio |
1 |
trans |
NA |
| Fasting insulin |
0.0168 |
0.00656 |
0.0103 |
Wald ratio |
1 |
trans |
NA |
| Ischemic stroke |
0.0771 |
0.0348 |
0.0269 |
Wald ratio |
1 |
trans |
NA |
| Height |
-0.0135 |
0.00622 |
0.0306 |
Wald ratio |
1 |
trans |
NA |
| Triglycerides |
0.021 |
0.00976 |
0.0311 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: iron deficiency anaemia |
0.132 |
0.0614 |
0.0313 |
Wald ratio |
1 |
trans |
NA |
| Endometrioid ovarian cancer |
0.129 |
0.0604 |
0.0328 |
Wald ratio |
1 |
trans |
NA |
| Lung cancer |
0.0742 |
0.0349 |
0.0333 |
Wald ratio |
1 |
trans |
NA |
| …and 112 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3628_3_4 |
MP2K2 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
89 association rows across 65 traits (82 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 |
| Hematological traits (multi-trait analysis) |
2e-131 |
rs350834 |
1 |
GCST90838669 |
no MR -> candidate analysis |
| Mean corpuscular volume (UKB data field 30040) |
2e-92 |
rs56267960 |
2 |
GCST90468086 |
no MR -> candidate analysis |
| Height |
8e-74 |
rs350897 |
7 |
GCST90245848 |
MR: beta=-0.0135, p=0.0306 (trans) |
| Red blood cell erythrocyte count (UKB data field 30010) |
9e-56 |
rs56267960 |
1 |
GCST90468098 |
no MR -> candidate analysis |
| red blood cell count (RBC, maximum, inv-norm transformed) |
8e-53 |
rs56267960 |
2 |
GCST90480668 |
no MR -> candidate analysis |
| Red blood cell count |
6e-52 |
rs56267960 |
2 |
GCST90662905 |
MR: beta=0.00471, p=0.282 (trans) |
| red blood cell count (RBC, mean, inv-norm transformed) |
1e-49 |
rs56267960 |
2 |
GCST90480669 |
no MR -> candidate analysis |
| red blood cell count (RBC, minimum, inv-norm transformed) |
1e-35 |
rs56267960 |
1 |
GCST90480670 |
no MR -> candidate analysis |
| mean corpuscular volume (MCV, mean, inv-norm transformed) |
6e-27 |
rs56267960 |
1 |
GCST90475469 |
no MR -> candidate analysis |
| mean corpuscular hemoglobin (MCH, mean, inv-norm transformed |
8e-27 |
rs56267960 |
1 |
GCST90475445 |
no MR -> candidate analysis |
| mean corpuscular hemoglobin (MCH, minimum, inv-norm transfor |
3e-26 |
rs56267960 |
1 |
GCST90475449 |
no MR -> candidate analysis |
| Standing height (UKB data field 50) |
7e-25 |
rs72978905 |
1 |
GCST90468178 |
no MR -> candidate analysis |
| …and 53 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 501 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 |
| cardiofaciocutaneous syndrome |
0.89 |
— |
established (curated) |
no MR -> candidate analysis |
| Noonan syndrome |
0.761 |
— |
established (curated) |
no MR -> candidate analysis |
| RASopathy |
0.936 |
— |
established (curated) |
no MR -> candidate analysis |
| hypertrophic cardiomyopathy |
0.012 |
— |
established (curated) |
no MR -> candidate analysis |
| cardiofaciocutaneous syndrome 1 |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| Abnormality of the cardiovascular system |
0.683 |
— |
established (curated) |
no MR -> candidate analysis |
| neurofibromatosis-Noonan syndrome |
0.486 |
— |
established (curated) |
no MR -> candidate analysis |
Of the 7 rows above, 7 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 |
16 known modulators (Dual specificity mitogen-activated protein kinase kinase 2) |
| gnomAD constraint |
pLI=0.00025, LOEUF=0.773 — LoF-tolerant |
| GWAS Catalog |
106 unique SNPs / 226 rows |
| ClinVar |
1072 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 501 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 ‘MAP2K2’ and resolved to ‘Dual specificity mitogen-activated protein kinase kinase 2’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 1072 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 65 traits by best p-value, aggregated from 89 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/P36507 — 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/ENSG00000126934/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2964/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/MAP2K2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/MAP2K2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=MAP2K2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/MAP2K2 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:43:25 · 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