PDK4 Gene: Pyruvate Dehydrogenase Kinase 4 - Function, Disease, and Expression
Comprehensive resource on PDK4 (Pyruvate Dehydrogenase Kinase 4), including genomic data, expression, mutations, pathways, and clinical significance.
Gene Information Card
| Symbol | PDK4 |
|---|---|
| Full Name | Pyruvate Dehydrogenase Kinase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q21.3 |
| NCBI Gene ID | 5166 ncbi.nlm.nih.gov/gene/5166 |
| Ensembl ID | ENSG00000004799 |
| UniProt ID | Q16654 |
| OMIM ID | 602598 |
| HGNC ID | 8811 |
| Aliases | PDHK4; pyruvate dehydrogenase kinase isoform 4 |
Description
The PDK4 gene encodes pyruvate dehydrogenase kinase 4, a mitochondrial enzyme that phosphorylates and inhibits the pyruvate dehydrogenase complex (PDC), thereby regulating glucose metabolism and promoting fatty acid oxidation. PDK4 is highly expressed in heart, skeletal muscle, and liver, and is upregulated during fasting and in metabolic conditions such as diabetes. It plays a role in cancer metabolism and has been implicated in various diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | PDK4 upregulation reduces glucose oxidation, contributing to insulin resistance. | ClinVar, PMID: 14514684 |
| Heart Failure | Increased PDK4 expression impairs cardiac glucose oxidation, leading to energy deficit. | PMID: 21610017 |
| Cancer (e.g., breast, lung) | PDK4 promotes aerobic glycolysis (Warburg effect) and tumor growth. | COSMIC, PMID: 25494235 |
| Sepsis | PDK4 is upregulated in sepsis, contributing to metabolic dysfunction. | PMID: 26745678 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 20.1 | High |
| Skeletal Muscle | 15.3 | High |
| Liver | 12.8 | High |
| Kidney | 8.5 | Medium |
| Brain | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 18.5 | High expression |
| MCF7 (breast) | 12.0 | Moderate expression |
| A549 (lung) | 9.8 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare | Potential loss of function |
| c.457C>T (p.Arg153Cys) | Missense | Rare | Unknown effect |
| c.1000G>A (p.Gly334Ser) | Missense | Rare | Unknown effect |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in PDK4 are rare and may lead to increased pyruvate dehydrogenase activity, potentially affecting metabolic regulation.
Gain of Function (GOF)
Gain-of-function mutations are not well documented; overexpression is more common in disease states.
Dominant Negative (DN)
No dominant-negative mutations have been reported for PDK4.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein kinase activity |
| • pyruvate dehydrogenase (acetyl-transferring) kinase activity | • mitochondrion |
| • regulation of glucose metabolic process | • response to starvation |
Pathways
• Pyruvate metabolism
• Glucose metabolism
• Insulin signaling
• Metabolic reprogramming in cancer
Protein Summary
PDK4 is a 411-amino acid mitochondrial protein that belongs to the PDK family. It phosphorylates the E1 alpha subunit of the pyruvate dehydrogenase complex, inactivating it. This inhibits the conversion of pyruvate to acetyl-CoA, shifting metabolism towards fatty acid oxidation. PDK4 is regulated by hormones and nutrients, and its dysregulation is linked to metabolic diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDK4 Knockout HEK293 Cell Line | EDJ-KQ447 | Human | 5166 | Details Get a Quote |
| PDK4 Knockout A-549 Cell Line | EDJ-KQ20073 | Human | 5166 | Details Get a Quote |
| PDK4 Knockout HCT 116 Cell Line | EDJ-KQ20075 | Human | 5166 | Details Get a Quote |
| PDK4 Knockout HeLa Cell Line | EDJ-KQ20076 | Human | 5166 | Details Get a Quote |
| Pdk4 Knockout NIH 3T3 Cell Line | EDJ-KZ39 | Mouse | 27273 | Details Get a Quote |
| Pdk4 Knockout C2C12 Cell Line | EDJ-KZ389 | Mouse | 27273 | Details Get a Quote |
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