PFKL Gene - Phosphofructokinase Liver Type | Function, Mutations & Disease

PFKL encodes the liver-type subunit of phosphofructokinase (PFK), a key regulatory enzyme in glycolysis. PFK catalyzes the irreversible conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. The enzyme is a tetramer composed of muscle (PFKM), liver (PFKL), and platelet (PFKP) subunits. PFKL is the predominant isoform in the liver, kidney, and red blood cells. Mutations in PFKL are associated with glycogen storage disease type VII (Tarui disease) and hemolytic anemia.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glycolysis / Gluconeogenesis (KEGG: hsa00010)

• Fructose and mannose metabolism (KEGG: hsa00051)

• Pentose phosphate pathway (KEGG: hsa00030)

• HIF-1 signaling pathway (KEGG: hsa04066)

PFKL encodes the liver-type subunit (L) of phosphofructokinase-1 (PFK-1), a tetrameric enzyme that catalyzes the rate-limiting step of glycolysis. The L subunit is 780 amino acids long and contains an N-terminal catalytic domain and a C-terminal regulatory domain. PFKL is allosterically activated by fructose-2,6-bisphosphate and AMP, and inhibited by ATP and citrate. In the liver, PFKL integrates hormonal and metabolic signals to control glucose flux. Mutations in PFKL cause PFK deficiency, leading to glycogen storage disease type VII (Tarui disease) and hemolytic anemia. The protein is also implicated in cancer metabolism, where its overexpression supports aerobic glycolysis (Warburg effect).