ABAT Gene: 4-Aminobutyrate Aminotransferase - Function, Mutations, and Disease

The ABAT gene encodes 4-aminobutyrate aminotransferase (GABA transaminase), a mitochondrial enzyme that catalyzes the catabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) to succinic semialdehyde. This reaction is a key step in the GABA shunt, which links GABA degradation to the tricarboxylic acid cycle. Mutations in ABAT cause GABA-transaminase deficiency, a rare autosomal recessive disorder characterized by severe neurological symptoms including psychomotor retardation, hypotonia, and seizures. The enzyme is also implicated in other neurological conditions and is a target for certain antiepileptic drugs.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• GABA shunt (KEGG: map00471)

• Alanine

• aspartate and glutamate metabolism (KEGG: map00250)

• Butanoate metabolism (KEGG: map00650)

4-aminobutyrate aminotransferase (UniProt P80404) is a homodimeric mitochondrial enzyme composed of 500 amino acids. It uses pyridoxal phosphate as a cofactor to catalyze the reversible transamination of GABA to succinic semialdehyde, with alpha-ketoglutarate as the amino acceptor. The enzyme is highly expressed in liver and brain, and its deficiency leads to severe neurological phenotypes. Structural studies show that mutations affecting the active site or dimer interface impair catalytic activity.