TIGAR

Chr 12

TP53 induced glycolysis regulatory phosphatase

Also known as: C12orf5, FR2BP

NCBI Gene: 57103 ENSG00000078237 UniProt: Q9NQ88 OMIM: 610775

The TIGAR protein functions as a fructose-bisphosphatase that blocks glycolysis and redirects glucose metabolism into the pentose phosphate pathway, reducing cellular reactive oxygen species and protecting against oxidative stress. Mutations in TIGAR cause autosomal recessive primary microcephaly with simplified gyral pattern, a neurodevelopmental disorder affecting brain growth and cortical folding. The gene shows moderate constraint against loss-of-function variants, suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

This gene is regulated as part of the p53 tumor suppressor pathway and encodes a protein with sequence similarity to the bisphosphate domain of the glycolytic enzyme that degrades fructose-2,6-bisphosphate. The protein functions by blocking glycolysis and directing the pathway into the pentose phosphate shunt. Expression of this protein also protects cells from DNA damaging reactive oxygen species and provides some protection from DNA damage-induced apoptosis. The 12p13.32 region that includes this gene is paralogous to the 11q13.3 region. [provided by RefSeq, Jul 2008]

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

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.55

LOEUF

Mechanism· predicted