PDK3 Gene: Pyruvate Dehydrogenase Kinase 3
Regulator of Mitochondrial Metabolism and Charcot-Marie-Tooth Disease
Gene Information Card
| Symbol | PDK3 |
|---|---|
| Full Name | Pyruvate Dehydrogenase Kinase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp22.11 |
| NCBI Gene ID | 5165 ncbi.nlm.nih.gov/gene/5165 |
| Ensembl ID | ENSG00000167992 |
| UniProt ID | Q15120 |
| OMIM ID | 300906 |
| HGNC ID | 8811 |
| Aliases | PDK3, pyruvate dehydrogenase kinase isoform 3 |
Description
PDK3 encodes a mitochondrial protein that is a member of the pyruvate dehydrogenase kinase family. This kinase phosphorylates and inactivates the pyruvate dehydrogenase complex, thereby regulating the conversion of pyruvate to acetyl-CoA and linking glycolysis to the TCA cycle. Mutations in PDK3 are associated with Charcot-Marie-Tooth disease type X6 (CMTX6).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease X-linked dominant 6 (CMTX6) | Gain-of-function mutation (p.Arg158His) increases kinase activity, leading to hyperphosphorylation and inactivation of the pyruvate dehydrogenase complex, impairing mitochondrial energy metabolism in peripheral nerves. | OMIM #300905; PMID: 23806086 |
| Charcot-Marie-Tooth disease (general) | PDK3 mutations disrupt mitochondrial ATP production, causing axonal degeneration. | ClinVar; PMID: 23806086 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Skeletal Muscle | 9.8 | Medium |
| Brain | 6.5 | Low |
| Liver | 4.2 | Low |
| Kidney | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 8.7 | Cervical cancer cell line |
| HepG2 | 6.3 | Hepatocellular carcinoma |
| SH-SY5Y | 7.1 | Neuroblastoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.473G>A (p.Arg158His) | Missense | Rare (found in CMTX6 families) | Gain-of-function; increased kinase activity |
| c.1A>G (p.Met1?) | Start loss | Unknown | Likely loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Start loss mutations (e.g., p.Met1?) are predicted to abolish protein expression.
Gain of Function (GOF)
p.Arg158His increases PDK3 activity, leading to PDH complex inhibition.
Dominant Negative (DN)
Not reported for PDK3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pyruvate metabolism (KEGG: hsa00620)
• Metabolic pathways (KEGG: hsa01100)
• PDH complex regulation (Reactome: R-HSA-204174)
Protein Summary
PDK3 is a mitochondrial serine/threonine kinase that phosphorylates the E1 alpha subunit of the pyruvate dehydrogenase complex, inhibiting its activity. It plays a key role in metabolic switching between glycolysis and oxidative phosphorylation. The p.Arg158His gain-of-function mutation causes Charcot-Marie-Tooth disease type X6 by impairing mitochondrial energy production in neurons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDK3 Knockout HEK293 Cell Line | EDJ-KQ5434 | Human | 5165 | Details Get a Quote |
| PDK3 Knockout A-549 Cell Line | EDJ-KQ28609 | Human | 5165 | Details Get a Quote |
| PDK3 Knockout HCT 116 Cell Line | EDJ-KQ28610 | Human | 5165 | Details Get a Quote |
| PDK3 Knockout HeLa Cell Line | EDJ-KQ28611 | Human | 5165 | Details Get a Quote |
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