GLDC Gene - Glycine Decarboxylase: Function, Mutations, and Disease Associations

The GLDC gene encodes the glycine decarboxylase (P-protein) component of the glycine cleavage system, a mitochondrial multienzyme complex that catalyzes the oxidative cleavage of glycine into carbon dioxide, ammonia, and a methylene group transferred to tetrahydrofolate. This enzyme is essential for glycine metabolism and one-carbon metabolism. Mutations in GLDC are a major cause of nonketotic hyperglycinemia (glycine encephalopathy), an autosomal recessive disorder characterized by accumulation of glycine in body fluids and severe neurological symptoms. Altered GLDC expression has also been implicated in cancer cell proliferation.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glycine

• serine and threonine metabolism (KEGG: hsa00260)

• One carbon pool by folate (KEGG: hsa00670)

• Glycine cleavage system

Glycine decarboxylase (P-protein) is a mitochondrial enzyme that catalyzes the first step of the glycine cleavage system, decarboxylating glycine and transferring the methylamine group to lipoic acid. The protein is a homodimer of approximately 105 kDa subunits, requiring pyridoxal phosphate as a cofactor. It plays a critical role in maintaining glycine homeostasis and providing one-carbon units for biosynthetic processes. Deficiency leads to severe neurological disease, while overexpression may support cancer cell growth.