Protein Dossier — MAP2K4 (Dual specificity mitogen-activated protein kinase kinase 4)
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 |
| HDL cholesterol |
-0.169 |
0.0131 |
7.84e-38 |
Wald ratio |
1 |
trans |
0.992 |
| Triglycerides |
0.141 |
0.0127 |
1.43e-28 |
Wald ratio |
1 |
trans |
0.992 |
| Body mass index (BMI) |
0.0351 |
0.00922 |
1.43e-04 |
Wald ratio |
1 |
trans |
NA |
| Eye problems or disorders: Diabetes related eye disease |
0.302 |
0.088 |
5.91e-04 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt |
0.259 |
0.0795 |
0.00114 |
Wald ratio |
1 |
trans |
NA |
| Fractured bone site(s): Wrist |
0.166 |
0.0559 |
0.00295 |
Wald ratio |
1 |
trans |
NA |
| Sleep duration |
-0.0213 |
0.0072 |
0.00314 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: deep venous thrombosis (dvt) |
0.154 |
0.0563 |
0.00637 |
Wald ratio |
1 |
trans |
NA |
| Hirschsprung’s disease |
-1.48 |
0.57 |
0.00932 |
Wald ratio |
1 |
trans |
NA |
| Caudate volume |
-47.8 |
18.6 |
0.0101 |
Wald ratio |
1 |
trans |
NA |
| Hippocampus volume |
-45.9 |
17.9 |
0.0102 |
Wald ratio |
1 |
trans |
NA |
| Putamen volume |
-57.8 |
22.7 |
0.0111 |
Wald ratio |
1 |
trans |
NA |
| …and 86 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5242_37_3 |
MP2K4 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
196 association rows across 71 traits (174 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-41 |
rs11653406 |
2 |
GCST90245848 |
no MR -> candidate analysis |
| Ascending aorta diameter |
6e-30 |
rs7215383 |
2 |
GCST90267390 |
no MR -> candidate analysis |
| Ascending thoracic aortic diameter |
5e-29 |
rs7215383 |
2 |
GCST90094400 |
no MR -> candidate analysis |
| Male-pattern baldness |
3e-26 |
rs2529703 |
2 |
GCST007020 |
no MR -> candidate analysis |
| Chronic obstructive pulmonary disease liability (machine lea |
5e-25 |
rs5819355 |
1 |
GCST90244098 |
no MR -> candidate analysis |
| Ascending aorta minimum area |
2e-23 |
rs7215383 |
1 |
GCST90093370 |
no MR -> candidate analysis |
| Ascending aorta maximum area |
2e-22 |
rs7215383 |
2 |
GCST90137440 |
no MR -> candidate analysis |
| Inguinal hernia |
2e-22 |
rs12453693 |
7 |
GCST90239727 |
MR: beta=-0.0441, p=0.456 (trans) |
| heart rate (HR, minimum, inv-normal transformed) |
3e-21 |
rs4614769 |
2 |
GCST90476341 |
no MR -> candidate analysis |
| FEV1/FVC ratio |
4e-21 |
rs56130357 |
1 |
GCST90705072 |
no MR -> candidate analysis |
| JT interval |
6e-21 |
rs4614769 |
2 |
GCST90179157 |
no MR -> candidate analysis |
| Ascending aorta maximum area (MTAG) |
6e-20 |
rs7215383 |
1 |
GCST90137450 |
no MR -> candidate analysis |
| …and 59 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 481 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 |
| breast carcinoma |
0.344 |
— |
common-variant locus |
no MR -> candidate analysis |
| lymphatic system disorder |
0.5 |
— |
common-variant locus |
no MR -> candidate analysis |
| Varicose veins |
0.5 |
— |
common-variant locus |
no MR -> candidate analysis |
| vein disorder |
0.5 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 4 rows above, 4 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 (Dual specificity mitogen-activated protein kinase kinase 4) |
| gnomAD constraint |
pLI=1, LOEUF=0.189 — LoF-INTOLERANT |
| GWAS Catalog |
82 unique SNPs / 159 rows |
| ClinVar |
73 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
1 clinical annotations across 1 drugs |
phenome — Top 30 of 481 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 ‘MAP2K4’ and resolved to ‘Dual specificity mitogen-activated protein kinase kinase 4’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 73 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 71 traits by best p-value, aggregated from 196 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/P45985 — 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/ENSG00000065559/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2897/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/MAP2K4 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/MAP2K4 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=MAP2K4%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=MAP2K4 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/MAP2K4 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:43:41 · 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