FBP2: Fructose-Bisphosphatase 2 – Key Regulator of Gluconeogenesis
Comprehensive genomic and proteomic overview of FBP2, a liver and kidney isozyme critical for glucose homeostasis.
Gene Information Card
| Symbol | FBP2 |
|---|---|
| Full Name | Fructose-Bisphosphatase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q31.1 |
| NCBI Gene ID | 2204 ncbi.nlm.nih.gov/gene/2204 |
| Ensembl ID | ENSG00000143178 |
| UniProt ID | O00757 |
| OMIM ID | 603027 |
| HGNC ID | 3607 |
| Aliases | FBPase 2, D-fructose-1,6-bisphosphate 1-phosphohydrolase 2 |
Description
FBP2 encodes fructose-bisphosphatase 2, a homotetrameric enzyme that catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate, a rate-limiting step in gluconeogenesis. This isozyme is predominantly expressed in the liver and kidney, with lower levels in other tissues. FBP2 is allosterically inhibited by AMP and fructose 2,6-bisphosphate, and activated by citrate. Mutations in FBP2 cause fructose-1,6-bisphosphatase deficiency, leading to hypoglycemia and metabolic acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fructose-1,6-bisphosphatase deficiency | Loss-of-function mutations impair gluconeogenesis, causing fasting hypoglycemia and lactic acidosis. | ClinVar, OMIM |
| Hypoglycemia, ketotic | Deficient FBP2 activity leads to impaired glucose production during fasting. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Small intestine | 2.1 | Low |
| Pancreas | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.2 | Liver cancer cell line |
| HEK293 | 0.5 | Embryonic kidney, low expression |
| Caco-2 | 1.8 | Colorectal adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.841G>A (p.Gly281Arg) | Missense | Rare | Loss of enzyme activity; associated with FBPase deficiency |
| c.960_961del (p.Leu321fs) | Frameshift | Rare | Truncated protein; loss of function |
| c.490C>T (p.Arg164Trp) | Missense | Rare | Reduced catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations in FBP2 are loss-of-function, leading to fructose-1,6-bisphosphatase deficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported in FBP2.
Dominant Negative (DN)
No dominant-negative mutations have been described for FBP2.
View complete mutation data：
Gene Ontology (GO)
| • fructose 1 (GO:0042132) | • gluconeogenesis (GO:0006094) |
| • carbohydrate metabolic process (GO:0005975) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) |
Pathways
• Gluconeogenesis (Reactome: R-HSA-70263)
• Fructose metabolism (KEGG: hsa00051)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
Fructose-bisphosphatase 2 (FBP2) is a 337-amino acid homotetrameric enzyme (UniProt O00757) that catalyzes the irreversible dephosphorylation of fructose 1,6-bisphosphate to fructose 6-phosphate, a key control point in gluconeogenesis. The protein is allosterically regulated by AMP and fructose 2,6-bisphosphate (inhibitors) and citrate (activator). FBP2 is essential for maintaining blood glucose during fasting; deficiency results in severe hypoglycemia and metabolic acidosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBP2 Knockout HEK293 Cell Line | EDJ-KQ1864 | Human | 8789 | Details Get a Quote |
| FBP2 Knockout HeLa Cell Line | EDJ-KQ55006 | Human | 8789 | Details Get a Quote |
| FBP2 Knockout A-549 Cell Line | EDJ-KQ63490 | Human | 8789 | Details Get a Quote |
| FBP2 Knockout HCT 116 Cell Line | EDJ-KQ71959 | Human | 8789 | Details Get a Quote |
