PFKFB1 Gene: Function, Expression, and Disease Associations

The PFKFB1 gene encodes a bifunctional enzyme that both synthesizes and degrades fructose-2,6-bisphosphate, a key allosteric regulator of glycolysis. The enzyme has two distinct catalytic domains: a 6-phosphofructo-2-kinase domain and a fructose-2,6-bisphosphatase domain. PFKFB1 is primarily expressed in liver, kidney, and pancreatic islets, and its activity is regulated by phosphorylation and allosteric effectors. Alternative splicing generates tissue-specific isoforms with different kinetic properties.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glycolysis / Gluconeogenesis (KEGG: hsa00010)

• Fructose and mannose metabolism (KEGG: hsa00051)

• Insulin signaling pathway (KEGG: hsa04910)

The PFKFB1 protein is a bifunctional enzyme of 471 amino acids (isoform 1) that contains both a kinase domain (N-terminal) and a phosphatase domain (C-terminal). It catalyzes the synthesis and degradation of fructose-2,6-bisphosphate, a potent allosteric activator of phosphofructokinase-1 (PFK-1). The enzyme is regulated by phosphorylation at Ser-32 by cAMP-dependent protein kinase (PKA), which activates the phosphatase activity and inhibits the kinase activity, thereby reducing fructose-2,6-bisphosphate levels and promoting gluconeogenesis. Tissue-specific isoforms arise from alternative splicing, with the liver isoform (L-type) being the most studied.