PFKFB3
6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 3
Gene Information Card
| Symbol | PFKFB3 |
|---|---|
| Full Name | 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 10p14 |
| NCBI Gene ID | 5209 ncbi.nlm.nih.gov/gene/5209 |
| Ensembl ID | ENSG00000170525 |
| UniProt ID | Q16875 |
| OMIM ID | 605842 |
| HGNC ID | 8874 |
| Aliases | iPFK2, PFK2, 6PF2K, IPFK2, RP1-278O19.1 |
Description
PFKFB3 encodes a bifunctional enzyme that both synthesizes and degrades fructose-2,6-bisphosphate, a potent allosteric activator of phosphofructokinase-1 (PFK-1), a key regulatory enzyme in glycolysis. The protein is involved in the control of glycolytic flux and is highly expressed in proliferating cells, including cancer cells, where it supports the Warburg effect. PFKFB3 also plays roles in angiogenesis, cell cycle progression, and inflammation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Overexpression of PFKFB3 increases fructose-2,6-bisphosphate levels, enhancing glycolysis and promoting tumor growth and survival. | PMID: 22926558, PMID: 26095358 |
| Pulmonary Hypertension | PFKFB3 upregulation in pulmonary artery smooth muscle cells drives glycolytic shift and vascular remodeling. | PMID: 27889600 |
| Inflammatory Bowel Disease | PFKFB3-mediated glycolysis in immune cells contributes to chronic inflammation. | PMID: 28783719 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Lymph Node | 10.2 | Medium |
| Spleen | 9.8 | Medium |
| Lung | 7.1 | Medium |
| Brain | 6.3 | Medium |
| Heart | 4.5 | Low |
| Liver | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical cancer cell line |
| MCF7 | 12.8 | Breast cancer cell line |
| A549 | 11.5 | Lung cancer cell line |
| HEK293 | 8.9 | Embryonic kidney cell line |
| HUVEC | 14.1 | Endothelial cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1048G>A (p.Glu350Lys) | Missense | <0.1% | Reported in COSMIC; functional impact unknown |
| c.1162C>T (p.Arg388Trp) | Missense | <0.1% | Reported in COSMIC; potential loss of kinase activity |
| c.1370A>G (p.Asn457Ser) | Missense | <0.1% | Reported in COSMIC; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce kinase activity (e.g., Arg388Trp) may impair glycolysis regulation.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported.
Dominant Negative (DN)
Not described for PFKFB3.
View complete mutation data：
Gene Ontology (GO)
| • fructose-2 | • 6-bisphosphate 2-phosphatase activity |
| • 6-phosphofructo-2-kinase activity | • ATP binding |
| • glycolytic process | • fructose 2 |
| • 6-bisphosphate metabolic process | • positive regulation of glycolysis |
| • angiogenesis |
Pathways
• Glycolysis / Gluconeogenesis
• Fructose and mannose metabolism
• HIF-1 signaling pathway
• Metabolic reprogramming in cancer
Protein Summary
PFKFB3 is a bifunctional enzyme with both kinase and phosphatase domains. It catalyzes the synthesis and degradation of fructose-2,6-bisphosphate, a key allosteric activator of PFK-1. The protein is a homodimer and is regulated by phosphorylation, acetylation, and ubiquitination. PFKFB3 is highly expressed in proliferating and cancer cells, where it promotes aerobic glycolysis (Warburg effect). It also localizes to the nucleus and influences cell cycle progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PFKFB3 Knockout HEK293 Cell Line | EDJ-KQ14733 | Human | 5209 | Details Get a Quote |
| PFKFB3 Knockout HeLa Cell Line | EDJ-KQ18050 | Human | 5209 | Details Get a Quote |
| PFKFB3 Knockout A-549 Cell Line | EDJ-KQ21150 | Human | 5209 | Details Get a Quote |
| PFKFB3 Knockout HCT 116 Cell Line | EDJ-KQ21151 | Human | 5209 | Details Get a Quote |
| PFKFB3 Knockout Huh-7 Cell Line | EDJ-KZ390 | Human | 5209 | Details Get a Quote |
