TALDO1 Gene: Function, Mutations, and Associated Diseases

The TALDO1 gene encodes transaldolase 1, a key enzyme in the non-oxidative branch of the pentose phosphate pathway (PPP). It catalyzes the reversible transfer of a dihydroxyacetone moiety from fructose-6-phosphate to erythrose-4-phosphate, generating sedoheptulose-7-phosphate and glyceraldehyde-3-phosphate. This enzyme is critical for cellular NADPH production, ribose-5-phosphate synthesis for nucleotide biosynthesis, and metabolic homeostasis. Mutations in TALDO1 cause transaldolase deficiency, a rare autosomal recessive disorder characterized by liver cirrhosis, splenomegaly, and neurological symptoms. Altered TALDO1 expression is also implicated in cancer metabolism.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Pentose phosphate pathway (non-oxidative branch) – Reactome R-HSA-71336

• Metabolism of carbohydrates – Reactome R-HSA-71387

• Glucose metabolism – KEGG hsa00030

Transaldolase 1 is a 337-amino acid protein (37.5 kDa) that forms a homodimer in the cytoplasm. It catalyzes a key reversible reaction in the non-oxidative pentose phosphate pathway, linking glycolysis to nucleotide biosynthesis. The enzyme is highly expressed in tissues with active lipid and nucleotide synthesis, such as liver and adipose tissue. Structural studies show a TIM barrel fold with a conserved active site. Deficiency leads to accumulation of sedoheptulose-7-phosphate and erythritol, causing multi-organ pathology.