PFKFB4
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4
Gene Information Card
| Symbol | PFKFB4 |
|---|---|
| Full Name | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 5210 ncbi.nlm.nih.gov/gene/5210 |
| Ensembl ID | ENSG00000114268 |
| UniProt ID | Q16877 |
| OMIM ID | 605320 |
| HGNC ID | 8875 |
| Aliases | PFK-2/FBPase-4, 6PF-2-K/Fru-2,6-P2ase 4 |
Description
PFKFB4 is a member of the PFKFB family of bifunctional enzymes that synthesize and degrade fructose-2,6-bisphosphate, a key allosteric regulator of glycolysis and gluconeogenesis. The enzyme contains both 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase activities. PFKFB4 is overexpressed in several cancers and plays a role in metabolic reprogramming, promoting glycolysis and tumor growth.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of PFKFB4 enhances glycolytic flux and supports tumor proliferation | PMID: 22926525 |
| Prostate cancer | PFKFB4 promotes androgen receptor signaling and metabolic adaptation | PMID: 24995982 |
| Glioblastoma | PFKFB4 upregulation correlates with poor prognosis and increased glycolysis | PMID: 25605294 |
| Lung cancer | PFKFB4 expression is elevated and associated with metabolic reprogramming | PMID: 27323847 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Liver | 4.1 | Low |
| Heart | 3.2 | Low |
| Kidney | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression |
| PC3 (prostate cancer) | 12.8 | High expression |
| A549 (lung cancer) | 10.5 | Medium expression |
| HEK293 (embryonic kidney) | 6.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | 0.02% | Unknown functional effect |
| c.1246G>A (p.Gly416Arg) | Missense | 0.01% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in PFKFB4.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in PFKFB4.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported in PFKFB4.
View complete mutation data：
Gene Ontology (GO)
| • 6-phosphofructo-2-kinase activity (GO:0003873) | • fructose-2 (GO:0004331) |
| • fructose metabolic process (GO:0006000) | • fructose 2 (GO:0006003) |
| • glycolytic process (GO:0006096) | • cytosol (GO:0005829) |
Pathways
• Glycolysis / Gluconeogenesis (KEGG: hsa00010)
• Fructose and mannose metabolism (KEGG: hsa00051)
• Metabolic reprogramming in cancer (Reactome: R-HSA-2262752)
Protein Summary
PFKFB4 is a bifunctional enzyme (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) that controls the cellular levels of fructose-2,6-bisphosphate, a potent allosteric activator of phosphofructokinase-1 (PFK1). By modulating PFK1 activity, PFKFB4 regulates the rate of glycolysis. The enzyme is composed of an N-terminal kinase domain and a C-terminal phosphatase domain. PFKFB4 is highly expressed in testis and certain cancers, where it supports the Warburg effect by promoting glycolytic flux. Its activity is regulated by phosphorylation and cellular energy status.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PFKFB4 Knockout HEK293 Cell Line | EDJ-KQ1862 | Human | 5210 | Details Get a Quote |
| PFKFB4 Knockout A-549 Cell Line | EDJ-KQ21731 | Human | 5210 | Details Get a Quote |
| PFKFB4 Knockout HCT 116 Cell Line | EDJ-KQ21732 | Human | 5210 | Details Get a Quote |
| PFKFB4 Knockout HeLa Cell Line | EDJ-KQ21733 | Human | 5210 | Details Get a Quote |
