Protein Dossier — PDK1 ([Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial)
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 |
| Ferritin |
0.0607 |
0.0196 |
0.00195 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: prostate cancer |
0.154 |
0.0501 |
0.00218 |
Wald ratio |
1 |
cis |
NA |
| Mean cell haemoglobin |
0.0567 |
0.0201 |
0.00484 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Other bones |
0.0472 |
0.0207 |
0.0223 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: enlarged prostate |
-0.0993 |
0.0471 |
0.0351 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: D25 Leiomyoma of uterus |
-0.0993 |
0.0486 |
0.0413 |
Wald ratio |
1 |
cis |
NA |
| Red blood cell count |
-0.00892 |
0.00437 |
0.0414 |
Wald ratio |
1 |
cis |
NA |
| Forearm bone mineral density |
0.0616 |
0.0327 |
0.0596 |
Wald ratio |
1 |
cis |
NA |
| Eye problems or disorders: Glaucoma |
0.0726 |
0.0388 |
0.0612 |
Wald ratio |
1 |
cis |
NA |
| Knee osteoarthritis |
-0.102 |
0.0545 |
0.0616 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt |
0.0934 |
0.0504 |
0.0638 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: high cholesterol |
0.0242 |
0.0131 |
0.0656 |
Wald ratio |
1 |
cis |
NA |
| …and 81 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5227_60_3 |
PDK1 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
7 association rows across 6 traits (3 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 |
8e-12 |
rs836624 |
2 |
GCST90245848 |
no MR -> candidate analysis |
| Insomnia |
4e-8 |
rs836603 |
1 |
GCST90131901 |
no MR -> candidate analysis |
| Crohn’s disease |
1e-6 |
rs151175749 |
1 |
GCST90446792 |
no MR -> candidate analysis |
| Gastric cancer |
2e-6 |
rs12693006 |
1 |
GCST90455528 |
no MR -> candidate analysis |
| Erectile dysfunction in type 1 diabetes |
2e-6 |
rs836589 |
1 |
GCST001572 |
no MR -> candidate analysis |
| Behenoyl sphingomyelin (d18:1/22:0) levels in elite athletes |
6e-6 |
rs12693006 |
1 |
GCST90133880 |
no MR -> candidate analysis |
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 488 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 |
| prostate carcinoma |
0.657 |
— |
common-variant locus |
no MR -> candidate analysis |
| brain cancer |
0.515 |
— |
common-variant locus |
no MR -> candidate analysis |
| Crohn disease |
0.498 |
— |
common-variant locus |
no MR -> candidate analysis |
| liver disorder |
0.484 |
— |
common-variant locus |
no MR -> candidate analysis |
| prostate cancer |
0.197 |
— |
common-variant locus |
MR: beta=0.154, p=0.00218 (cis) |
| mental disorder |
0.171 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 6 rows above, 5 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 (3-phosphoinositide-dependent protein kinase 1) |
| gnomAD constraint |
pLI=4.7e-10, LOEUF=0.94 — LoF-tolerant |
| GWAS Catalog |
46 unique SNPs / 82 rows |
| ClinVar |
100 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 488 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 ‘PDK1’ and resolved to ‘3-phosphoinositide-dependent protein kinase 1’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 100 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 6 of 6 traits by best p-value, aggregated from 7 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/Q15118 — 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/ENSG00000152256/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2534/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PDK1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PDK1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PDK1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PDK1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:16:30 · 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