Protein Dossier — MAPKAPK3 (MAP kinase-activated protein kinase 3)
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 |
| Non-cancer illness code self-reported: gout |
0.0475 |
0.0192 |
0.0131 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: N20 Calculus of kidney and ureter |
-0.0722 |
0.0307 |
0.0186 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: bladder problem (not cancer) |
0.0618 |
0.0295 |
0.0366 |
Wald ratio |
1 |
trans |
NA |
| Hirschsprung’s disease |
-0.299 |
0.146 |
0.04 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: pernicious anaemia |
-0.0998 |
0.0489 |
0.0411 |
Wald ratio |
1 |
trans |
NA |
| Body fat |
-0.0109 |
0.00534 |
0.042 |
Wald ratio |
1 |
trans |
NA |
| Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis |
0.643 |
0.317 |
0.0425 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: G47 Sleep disorders |
0.0582 |
0.0295 |
0.0483 |
Wald ratio |
1 |
trans |
NA |
| Neo-neuroticism |
0.182 |
0.0929 |
0.0504 |
Wald ratio |
1 |
trans |
NA |
| Neo-agreeableness |
-0.116 |
0.06 |
0.0526 |
Wald ratio |
1 |
trans |
NA |
| Lung cancer |
0.0335 |
0.0185 |
0.0701 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: hypertension |
0.00733 |
0.00405 |
0.0708 |
Wald ratio |
1 |
trans |
NA |
| …and 105 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3822_54_2 |
MAPKAPK3 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
24 association rows across 22 traits (22 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) |
8e-31 |
rs34492910 |
1 |
GCST90838669 |
no MR -> candidate analysis |
| MME/NT5E protein level ratio |
6e-25 |
rs112256201 |
1 |
GCST90315460 |
no MR -> candidate analysis |
| BAIAP2/MME protein level ratio |
3e-23 |
rs112256201 |
1 |
GCST90313453 |
no MR -> candidate analysis |
| BST2/MME protein level ratio |
3e-23 |
rs112256201 |
1 |
GCST90313539 |
no MR -> candidate analysis |
| SPINK8 protein levels |
4e-19 |
rs74422202 |
2 |
GCST90470726 |
no MR -> candidate analysis |
| eosinophil (absolute count, maximum, inv-norm transformed) |
5e-17 |
rs809451 |
1 |
GCST90479601 |
no MR -> candidate analysis |
| Reticulocyte percentage (UKB data field 30240) |
7e-17 |
rs114292886 |
1 |
GCST90468101 |
no MR -> candidate analysis |
| Reticulocyte count (UKB data field 30250) |
3e-16 |
rs114292886 |
1 |
GCST90468100 |
no MR -> candidate analysis |
| Educational attainment (MTAG) |
2e-15 |
rs11716398 |
1 |
GCST006571 |
no MR -> candidate analysis |
| Educational attainment (years of education) |
2e-14 |
rs11716398 |
1 |
GCST006442 |
no MR -> candidate analysis |
| Educational attainment |
3e-14 |
rs4261877 |
1 |
GCST90105038 |
no MR -> candidate analysis |
| Total cholesterol levels |
2e-9 |
rs41308269 |
1 |
GCST90239676 |
no MR -> candidate analysis |
| …and 10 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 133 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 |
| patterned macular dystrophy 3 |
0.615 |
— |
established (curated) |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.312 |
— |
common-variant locus |
no MR -> candidate analysis |
| Retinal dystrophy |
0.182 |
— |
established (curated) |
no MR -> candidate analysis |
| Alzheimer disease |
0.179 |
— |
common-variant locus |
no MR -> candidate analysis |
| placental abruption |
0.117 |
— |
common-variant locus |
no MR -> candidate analysis |
| schizophrenia |
0.115 |
— |
common-variant locus |
MR: beta=-0.00924, p=0.383 (trans) |
| cystitis |
0.106 |
— |
common-variant locus |
no MR -> candidate analysis |
| breast cancer |
0.068 |
— |
common-variant locus |
MR: beta=0.00562, p=0.369 (trans) |
| mathematical ability |
0.066 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 9 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 |
0 known modulators (MAP kinase-activated protein kinase 3) |
| gnomAD constraint |
pLI=5.3e-09, LOEUF=0.943 — LoF-tolerant |
| GWAS Catalog |
58 unique SNPs / 116 rows |
| ClinVar |
335 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 133 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 ‘MAPKAPK3’ and resolved to ‘MAP kinase-activated protein kinase 3’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 335 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 22 traits by best p-value, aggregated from 24 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/Q16644 — 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/ENSG00000114738/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4670/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/MAPKAPK3 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/MAPKAPK3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=MAPKAPK3%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/MAPKAPK3 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:44:28 · 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