GPD2 (Glycerol-3-Phosphate Dehydrogenase 2): Key Roles in Metabolism and Disease
Explore the GPD2 gene, its protein product, tissue expression, associated diseases, and clinical significance.
Gene Information Card
| Symbol | GPD2 |
|---|---|
| Full Name | Glycerol-3-Phosphate Dehydrogenase 2 |
| Gene Type | protein coding |
| Chromosomal Location | 2q24.1 |
| NCBI Gene ID | 2820 ncbi.nlm.nih.gov/gene/2820 |
| Ensembl ID | ENSG00000115159 |
| UniProt ID | P43304 |
| OMIM ID | 138430 |
| HGNC ID | 4456 |
| Aliases | GPDM, mGPDH, mtGPDH |
Description
GPD2 encodes the mitochondrial glycerol-3-phosphate dehydrogenase, a flavin adenine dinucleotide (FAD)-dependent enzyme located on the inner mitochondrial membrane. It catalyzes the conversion of glycerol-3-phosphate to dihydroxyacetone phosphate, transferring electrons to the electron transport chain via ubiquinone. This enzyme is a key component of the glycerol phosphate shuttle, which regenerates cytosolic NAD+ and contributes to ATP production. GPD2 is involved in glucose metabolism, insulin secretion, and reactive oxygen species (ROS) generation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | Altered GPD2 activity affects glucose-stimulated insulin secretion in pancreatic beta cells; reduced expression may impair the glycerol phosphate shuttle and ATP production. | PMID: 10523018; PMID: 12145198 |
| Obesity | GPD2 expression in adipose tissue correlates with metabolic rate; variants may influence energy expenditure and fat accumulation. | PMID: 15690347 |
| Cancer | GPD2 is upregulated in certain tumors, promoting glycolysis and metastasis via ROS production and mitochondrial metabolism. | PMID: 28935771; COSMIC |
| Hyperinsulinemic Hypoglycemia | Mutations in GPD2 have been associated with familial hyperinsulinism, though evidence is limited. | OMIM: 138430 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.4 | Medium |
| Kidney | 10.8 | Medium |
| Heart | 8.9 | Low |
| Skeletal Muscle | 7.2 | Low |
| Pancreas | 6.5 | Low |
| Brain | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Liver cancer cell line; high expression |
| A549 | 8.7 | Lung carcinoma; moderate |
| MCF7 | 6.2 | Breast cancer; low |
| K562 | 4.5 | Leukemia; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1096C>T (p.Arg366Cys) | Missense | Rare | Reported in hyperinsulinemic hypoglycemia; may reduce enzyme activity |
| c.1150G>A (p.Gly384Ser) | Missense | Rare | Potential loss-of-function; associated with metabolic disorders |
| c.1367A>G (p.Asn456Ser) | Missense | Rare | Uncertain significance; may affect protein stability |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in GPD2 are rare and may impair glycerol phosphate shuttle, leading to reduced ATP production and altered insulin secretion.
Gain of Function (GOF)
Gain-of-function mutations are not well documented; overexpression in cancer suggests potential oncogenic role.
Dominant Negative (DN)
No dominant-negative effects have been reported for GPD2.
View complete mutation data：
Gene Ontology (GO)
| • glycerol-3-phosphate dehydrogenase activity | • FAD binding |
| • mitochondrial inner membrane | • glycerol-3-phosphate metabolic process |
| • electron transport chain | • NADH oxidation |
| • insulin secretion |
Pathways
• Glycerol phosphate shuttle
• Glycerophospholipid metabolism
• Thermogenesis
• Glucose metabolism
Protein Summary
GPD2 is a 727-amino acid protein (UniProt P43304) localized to the mitochondrial inner membrane. It contains a flavin adenine dinucleotide (FAD) binding domain and a glycerol-3-phosphate binding domain. The protein forms homodimers and transfers electrons from glycerol-3-phosphate to ubiquinone in the electron transport chain. It plays a critical role in the glycerol phosphate shuttle, regulating the NAD+/NADH ratio and contributing to cellular redox balance. GPD2 is also involved in reactive oxygen species production and has been implicated in metabolic diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPD2 Knockout HEK293 Cell Line | EDJ-KQ4749 | Human | 2820 | Details Get a Quote |
| GPD2 Knockout A-549 Cell Line | EDJ-KQ27503 | Human | 2820 | Details Get a Quote |
| GPD2 Knockout HCT 116 Cell Line | EDJ-KQ27504 | Human | 2820 | Details Get a Quote |
| GPD2 Knockout HeLa Cell Line | EDJ-KQ27505 | Human | 2820 | Details Get a Quote |
