GLA (gene)

GLA is a human gene that provides instructions for making an enzyme called alpha-galactosidase A. This enzyme is a lysosomal hydrolase, meaning it functions within lysosomes (cellular compartments responsible for breaking down and recycling materials) to break down specific lipids called globotriaosylceramide (Gb3), also known as ceramide trihexoside (CTH), and related glycolipids.

Defects in the GLA gene cause Fabry disease, a lysosomal storage disorder. Mutations in this gene lead to a deficiency or absence of the alpha-galactosidase A enzyme. This deficiency prevents the proper breakdown of Gb3, causing it to accumulate in cells throughout the body, particularly in the kidneys, heart, and nervous system.

The GLA gene is located on the X chromosome (Xq22.1). Because males have only one X chromosome, a single mutated copy of the GLA gene is sufficient to cause Fabry disease. Females, with two X chromosomes, may experience a wider range of symptoms depending on the pattern of X-chromosome inactivation.

The enzyme alpha-galactosidase A consists of two identical subunits. The gene itself spans approximately 12.8 kb and contains 7 exons.

Testing for mutations in the GLA gene is used to confirm a diagnosis of Fabry disease, especially in individuals with atypical presentations or females who may be carriers.