PCK1: Phosphoenolpyruvate Carboxykinase 1 (Soluble)
Key enzyme in gluconeogenesis, linked to metabolic disorders and cancer
Gene Information Card
| Symbol | PCK1 |
|---|---|
| Full Name | Phosphoenolpyruvate Carboxykinase 1 (Soluble) |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.31 |
| NCBI Gene ID | 5105 ncbi.nlm.nih.gov/gene/5105 |
| Ensembl ID | ENSG00000124253 |
| UniProt ID | P35558 |
| OMIM ID | 261680 |
| HGNC ID | 8724 |
| Aliases | PEPCK1, PEPCKC, PCK1C |
Description
PCK1 encodes the cytosolic isozyme of phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in gluconeogenesis that catalyzes the conversion of oxaloacetate to phosphoenolpyruvate. The gene is primarily expressed in liver, kidney, and adipose tissue, and its expression is regulated by hormones such as insulin, glucagon, and glucocorticoids. Mutations in PCK1 are associated with metabolic disorders including diabetes and obesity, and altered expression is implicated in cancer cell metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cytosolic PEPCK deficiency | Loss-of-function mutations impair gluconeogenesis, leading to hypoglycemia and metabolic acidosis | OMIM #261680 |
| Type 2 diabetes | Dysregulated PCK1 expression contributes to hepatic insulin resistance and increased gluconeogenesis | NCBI Gene, ClinVar |
| Hepatocellular carcinoma | PCK1 downregulation promotes aerobic glycolysis (Warburg effect) and tumor growth | COSMIC, literature |
| Obesity | Altered PCK1 activity in adipose tissue affects glyceroneogenesis and lipid metabolism | OMIM, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 38.5 | High |
| Kidney | 22.1 | Medium |
| Adipose tissue | 15.3 | Medium |
| Small intestine | 8.7 | Low |
| Pancreas | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 42.0 | High expression |
| HEK293 (kidney) | 18.5 | Moderate expression |
| MCF7 (breast) | 3.2 | Low expression |
| A549 (lung) | 1.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.925G>A (p.Gly309Arg) | Missense | <0.01% | Loss of enzyme activity; associated with PEPCK deficiency |
| c.1144C>T (p.Arg382Trp) | Missense | <0.01% | Reduced catalytic efficiency; reported in metabolic acidosis |
| c.1468G>A (p.Glu490Lys) | Missense | <0.01% | Impaired protein stability; ClinVar pathogenic |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Gly309Arg, p.Arg382Trp) reduce or abolish PEPCK activity, impairing gluconeogenesis and causing hypoglycemia.
Gain of Function (GOF)
Not well documented; overexpression in liver is linked to insulin resistance but not specific gain-of-function mutations.
Dominant Negative (DN)
No dominant-negative mutations reported; PCK1 deficiency is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004613 - phosphoenolpyruvate carboxykinase (GTP) activity | • GO:0006094 - gluconeogenesis |
| • GO:0005737 - cytoplasm | • GO:0005829 - cytosol |
| • GO:0016787 - hydrolase activity | • GO:0042593 - glucose homeostasis |
Pathways
• Gluconeogenesis (Reactome: R-HSA-70263)
• Metabolism of carbohydrates (Reactome: R-HSA-71387)
• Insulin signaling pathway (KEGG: hsa04910)
• PPAR signaling pathway (KEGG: hsa03320)
Protein Summary
PCK1 encodes a 622-amino acid cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) that catalyzes the GTP-dependent decarboxylation of oxaloacetate to phosphoenolpyruvate, the first committed step in gluconeogenesis. The protein is a homotetramer and is allosterically regulated by nucleotides. It plays a central role in hepatic glucose production, renal gluconeogenesis, and adipose glyceroneogenesis. Post-translational modifications include acetylation and phosphorylation, which modulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PCK1 Knockout HEK293 Cell Line | EDJ-KQ841 | Human | 5105 | Details Get a Quote |
| PCK1 Knockout Hep-G2 Cell Line | EDJ-KZ385 | Human | 5105 | Details Get a Quote |
| PCK1 Knockout HeLa Cell Line | EDJ-KQ54092 | Human | 5105 | Details Get a Quote |
| PCK1 Knockout A-549 Cell Line | EDJ-KQ62580 | Human | 5105 | Details Get a Quote |
| PCK1 Knockout HCT 116 Cell Line | EDJ-KQ71049 | Human | 5105 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
