FBP1 (Fructose-Bisphosphatase 1): A Key Metabolic Enzyme and Tumor Suppressor
Comprehensive genomic, functional, and clinical insights into FBP1, a rate-limiting gluconeogenesis enzyme implicated in metabolic disorders and cancer.
Gene Information Card
| Symbol | FBP1 |
|---|---|
| Full Name | Fructose-bisphosphatase 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 9q22.32 |
| NCBI Gene ID | 2203 ncbi.nlm.nih.gov/gene/2203 |
| Ensembl ID | ENSG00000165140 |
| UniProt ID | P09467 |
| OMIM ID | 611570 |
| HGNC ID | 3606 |
| Aliases | FBP; FBPase 1; GSD14 |
Description
FBP1 encodes fructose-1,6-bisphosphatase 1, a key regulatory enzyme in gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate. It is predominantly expressed in the liver and kidney, where it controls glucose production. Beyond its metabolic role, FBP1 functions as a tumor suppressor in several cancers by inhibiting glycolysis and modulating cellular signaling pathways. Mutations in FBP1 cause fructose-1,6-bisphosphatase deficiency, an autosomal recessive metabolic disorder characterized by hypoglycemia and lactic acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fructose-1,6-bisphosphatase deficiency | Loss-of-function mutations reduce enzyme activity, impairing gluconeogenesis and causing hypoglycemia and lactic acidosis. | OMIM #611570; ClinVar |
| Hepatocellular carcinoma | FBP1 downregulation promotes aerobic glycolysis (Warburg effect) and tumor growth; loss of FBP1 enhances β-catenin signaling. | COSMIC; PMID studies |
| Renal cell carcinoma | FBP1 loss leads to increased glycolysis and altered metabolic reprogramming, supporting tumor progression. | COSMIC; PMID studies |
| Pancreatic cancer | FBP1 silencing contributes to metabolic adaptation and chemoresistance. | COSMIC; PMID studies |
| Breast cancer | FBP1 loss correlates with poor prognosis and promotes epithelial-mesenchymal transition. | COSMIC; PMID studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | ~200 | High |
| Kidney | ~150 | High |
| Small intestine | ~20 | Low |
| Skeletal muscle | ~5 | Not detected |
| Brain | ~2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | ~180 | High expression |
| HEK293 (embryonic kidney) | ~120 | Moderate expression |
| A549 (lung) | ~10 | Low expression |
| MCF7 (breast) | ~5 | Low expression |
| K562 (leukemia) | ~2 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.960_961insA (p.Thr321AsnfsTer5) | Frameshift | Rare | Loss of function; causes FBPase deficiency |
| c.841G>A (p.Gly281Arg) | Missense | Rare | Loss of function; reduced enzyme activity |
| c.485C>T (p.Pro162Leu) | Missense | Rare | Loss of function; impaired stability |
| c.976C>T (p.Arg326Trp) | Missense | Rare | Loss of function; catalytic defect |
| c.1145T>C (p.Leu382Pro) | Missense | Rare | Loss of function; structural disruption |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations in FBP1 are loss-of-function, leading to reduced or absent enzyme activity, causing fructose-1,6-bisphosphatase deficiency. In cancer, epigenetic silencing or deletion of FBP1 results in loss of tumor suppressor function.
Gain of Function (GOF)
No gain-of-function mutations have been reported for FBP1. The enzyme's activity is tightly regulated; activating mutations are not described in the literature.
Dominant Negative (DN)
No dominant-negative mutations have been documented for FBP1. The enzyme functions as a homotetramer, but pathogenic variants are typically recessive, requiring biallelic loss.
View complete mutation data：
Gene Ontology (GO)
| • fructose-1 | • 6-bisphosphate 1-phosphatase activity |
| • hydrolase activity | • metal ion binding |
| • gluconeogenesis | • carbohydrate metabolic process |
| • response to glucose | • negative regulation of glycolytic process |
| • regulation of insulin secretion |
Pathways
• Gluconeogenesis
• Fructose and mannose metabolism
• Metabolic reprogramming in cancer
• AMPK signaling
• Insulin signaling
Protein Summary
FBP1 is a homotetrameric enzyme that catalyzes the rate-limiting step in gluconeogenesis. It is allosterically inhibited by fructose-2,6-bisphosphate and AMP, and activated by ATP. The protein is predominantly cytosolic in liver and kidney. In cancer, FBP1 acts as a tumor suppressor by inhibiting glycolysis and promoting oxidative phosphorylation. It also interacts with β-catenin to suppress Wnt signaling. Post-translational modifications include phosphorylation and acetylation, which modulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBP1 Knockout HEK293 Cell Line | EDJ-KQ1863 | Human | 2203 | Details Get a Quote |
| IGFBP1 Knockout HEK293 Cell Line | EDJ-KQ3865 | Human | 3484 | Details Get a Quote |
| FGFBP1 Knockout HEK293 Cell Line | EDJ-KQ6205 | Human | 9982 | Details Get a Quote |
| PMFBP1 Knockout HEK293 Cell Line | EDJ-KQ9845 | Human | 83449 | Details Get a Quote |
| IGFBP1 Knockout HeLa Cell Line | EDJ-KQ26061 | Human | 3484 | Details Get a Quote |
| FBP1 Knockout HeLa Cell Line | EDJ-KQ21734 | Human | 2203 | Details Get a Quote |
| IGFBP1 Knockout A-549 Cell Line | EDJ-KQ24704 | Human | 3484 | Details Get a Quote |
| FGFBP1 Knockout A-549 Cell Line | EDJ-KQ31408 | Human | 9982 | Details Get a Quote |
| FGFBP1 Knockout HCT 116 Cell Line | EDJ-KQ31409 | Human | 9982 | Details Get a Quote |
| FGFBP1 Knockout HeLa Cell Line | EDJ-KQ31410 | Human | 9982 | Details Get a Quote |
| PMFBP1 Knockout HCT 116 Cell Line | EDJ-KQ36701 | Human | 83449 | Details Get a Quote |
| PMFBP1 Knockout HeLa Cell Line | EDJ-KQ36702 | Human | 83449 | Details Get a Quote |
| FBP1 Knockout A-549 Cell Line | EDJ-KQ61682 | Human | 2203 | Details Get a Quote |
| PMFBP1 Knockout A-549 Cell Line | EDJ-KQ65943 | Human | 83449 | Details Get a Quote |
| FBP1 Knockout HCT 116 Cell Line | EDJ-KQ70168 | Human | 2203 | Details Get a Quote |
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