PDK3
Chr XXLDpyruvate dehydrogenase kinase 3
Also known as: CMTX6, GS1-358P8.4
PDK3 encodes pyruvate dehydrogenase kinase 3, which inhibits the pyruvate dehydrogenase complex by phosphorylating its E1 subunit, thereby regulating the conversion of pyruvate to acetyl-CoA and controlling glucose metabolism. Mutations cause X-linked dominant Charcot-Marie-Tooth disease type 6, a peripheral neuropathy. The gene is predominantly expressed in heart and skeletal muscle and shows moderate constraint against loss-of-function variants (LOEUF 0.546).
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PDK3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools