PFKFB3

Chr 10

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3

Also known as: IPFK2, PFK2, iPFK-2

NCBI Gene: 5209 ENSG00000170525 UniProt: Q16875 OMIM: 605319

The protein catalyzes both the synthesis and degradation of fructose 2,6-bisphosphate, a key regulatory molecule controlling glycolysis and linking glucose metabolism to cell cycle progression. Mutations cause autosomal recessive glycogen storage disease type XII, which presents with hemolytic anemia, muscle weakness, and cardiac abnormalities. The gene shows moderate constraint to loss-of-function variation (LOEUF 0.447), consistent with its essential metabolic function.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to a family of bifunctional proteins that are involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate (F2,6BP), and a fructose-2,6-biphosphatase activity that catalyzes the degradation of F2,6BP. This protein is required for cell cycle progression and prevention of apoptosis. It functions as a regulator of cyclin-dependent kinase 1, linking glucose metabolism to cell proliferation and survival in tumor cells. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

245

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

—

Mechanism