HEXA

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HEXA is a human gene on chromosome 15 that makes the alpha subunit of the enzyme hexosaminidase A. This enzyme works with a beta subunit to break down GM2 gangliosides inside lysosomes, with help from the GM2 activator protein.

When HEXA is mutated, hexosaminidase A can’t do its job properly, leading to Tay-Sachs disease. In this disease, GM2 gangliosides build up in brain and spinal cord cells, causing rapid neurodegeneration, loss of skills, seizures, and vision problems. Infantile Tay-Sachs is usually fatal by early childhood.

The beta subunit is encoded by HEXB; mutations in HEXB cause Sandhoff disease, a related condition where GM2 breakdown is also impaired.

A common HEXA mutation in many patients is a four-base-pair insertion (TATC) in exon 11 that creates an early stop, stopping production of functional enzyme.

Research uses HEXA knockout mice to study the disease. Some gene-therapy studies have used a non-replicating herpes simplex vector to deliver HEXA and restore enzyme activity in mice, reducing GM2 buildup and showing potential for future treatments.