PDK1 (Pyruvate Dehydrogenase Kinase 1)
A key regulator of glucose metabolism and mitochondrial function, implicated in cancer and metabolic disorders.
Gene Information Card
| Symbol | PDK1 |
|---|---|
| Full Name | Pyruvate Dehydrogenase Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q31.1 |
| NCBI Gene ID | 5163 ncbi.nlm.nih.gov/gene/5163 |
| Ensembl ID | ENSG00000152256 |
| UniProt ID | Q15118 |
| OMIM ID | 602524 |
| HGNC ID | 8809 |
| Aliases | PDHK1, PDHKD1, PDK1 |
Description
PDK1 (pyruvate dehydrogenase kinase 1) encodes a mitochondrial protein that phosphorylates and inactivates the pyruvate dehydrogenase complex (PDC), thereby inhibiting the conversion of pyruvate to acetyl-CoA and promoting anaerobic glycolysis. This gene is a key regulator of glucose metabolism and is frequently upregulated in cancer cells (Warburg effect).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | PDK1 overexpression inhibits PDC, promoting glycolysis and tumor growth | COSMIC, NCBI |
| Type 2 diabetes | PDK1 activity contributes to insulin resistance and metabolic inflexibility | OMIM #602524 |
| Lactic acidosis | Increased PDK1 activity reduces pyruvate oxidation, leading to lactate accumulation | NCBI Gene |
| Mitochondrial disorders | Dysregulation of PDK1 affects mitochondrial function and energy homeostasis | UniProt Q15118 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Skeletal Muscle | 10.2 | Medium |
| Liver | 6.8 | Low |
| Kidney | 8.1 | Medium |
| Brain | 7.3 | Low |
| Pancreas | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical cancer cell line |
| MCF7 | 12.1 | Breast cancer cell line |
| A549 | 14.7 | Lung cancer cell line |
| HepG2 | 9.8 | Liver cancer cell line |
| K562 | 6.5 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Loss of start codon, likely loss of function |
| c.101C>T (p.Thr34Met) | Missense | <0.1% | Unknown significance |
| c.202G>A (p.Glu68Lys) | Missense | <0.1% | Unknown significance |
| c.1000C>T (p.Arg334Trp) | Missense | <0.1% | Unknown significance |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Met1?) may lead to loss of PDK1 activity, reducing PDC inhibition and increasing oxidative metabolism.
Gain of Function (GOF)
Amplification or overexpression of PDK1 (not point mutations) is common in cancer, leading to constitutive PDC inhibition and enhanced glycolysis.
Dominant Negative (DN)
No dominant-negative mutations have been reported for PDK1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 (protein kinase activity) | • GO:0004740 (pyruvate dehydrogenase (acetyl-transferring) kinase activity) |
| • GO:0005739 (mitochondrion) | • GO:0006006 (glucose metabolic process) |
| • GO:0010906 (regulation of glucose metabolic process) | • GO:0042493 (response to drug) |
Pathways
• Glycolysis / Gluconeogenesis (Reactome R-HSA-70171)
• Pyruvate metabolism (Reactome R-HSA-70268)
• Regulation of pyruvate dehydrogenase complex (Reactome R-HSA-204174)
• HIF-1 signaling pathway (KEGG hsa04066)
• Insulin signaling pathway (KEGG hsa04910)
Protein Summary
PDK1 is a mitochondrial serine/threonine kinase that phosphorylates the E1 alpha subunit of the pyruvate dehydrogenase complex (PDC), inactivating it. This inhibits the conversion of pyruvate to acetyl-CoA, shifting metabolism toward glycolysis. PDK1 is highly expressed in heart and skeletal muscle and is overexpressed in many cancers, contributing to the Warburg effect. Its activity is regulated by ATP, NADH, and hypoxia-inducible factors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDK1 Knockout HEK293 Cell Line | EDJ-KQ1504 | Human | 5163 | Details Get a Quote |
| PDK1 Knockout A-549 Cell Line | EDJ-KQ21121 | Human | 5163 | Details Get a Quote |
| PDK1 Knockout HCT 116 Cell Line | EDJ-KQ21122 | Human | 5163 | Details Get a Quote |
| PDK1 Knockout HeLa Cell Line | EDJ-KQ21123 | Human | 5163 | Details Get a Quote |
| PDK1 Knockout HAP1 Cell Line | EDC07860 | Human | 5163 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
