The HEXB gene is located on chromosome 5q13.3, it gives instructions for making the beta subunit of two related enzymes, beta-hexosaminidase A and beta-hexosaminidase B.  Defects in the beta-hexosaminidase A and beta-hexosaminidase B enzymes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. 

At least 30 different mutations in this gene have been identified in patients with Sandhoff disease. The most common mutation that causes the severe form of the disease is a 16 kb deletion near the beginning of the HEXB gene, which results in a total loss of enzyme activity. 

The HEXB gene has 14 coding exons, and spans a region of about 83 kb in the genomic DNA. At least 30 different mutations in this gene have been identified in patients with Sandhoff disease. The most common mutation that causes the severe form of the disease is a 16 kb deletion near the beginning of the HEXB gene, which results in a total loss of enzyme activity. This mutation accounts for about 27% of the SD alleles among various ethnic groups.