ATP2B2

The ATP2B2 gene provides instructions for making an enzyme called plasma membrane calcium-transporting ATPase 2 (PMCA2). This enzyme belongs to a family of ATPase enzymes that helps control the level of positively charged calcium atoms (calcium ions) inside cells. Calcium ions act as signals for a large number of activities that are important for the normal development and function of cells. PMCA2 appears to be important for regulating calcium ion levels in certain cells in the brain, spinal cord, liver, inner ear, and in the breast when milk is produced.

Researchers are interested in PMCA2's role in hearing because of its presence in the inner ear. Hearing requires the conversion of sound waves to nerve impulses that are transmitted via the auditory nerve to the brain. This conversion process occurs in specialized cells called hair cells and is triggered by a rapid change in the level of certain ions, including calcium ions. Studies indicate that PMCA2 exports calcium ions from hair cells and contributes to changes in ion levels that are needed for the conversion of sound waves to nerve impulses.

nonsyndromic deafness - course of condition modified by variations in the ATP2B2 gene

Researchers have identified one variation in the ATP2B2 gene that appears to affect the severity of hearing loss. This variation changes one of the building blocks (amino acids) used to make the PMCA2 enzyme. Specifically, the amino acid valine is replaced with the amino acid methionine at position 586 in the enzyme (written as Val586Met). In a small number of people, researchers found that this particular variation occurs with mutations in another gene (called CDH23) that causes hearing loss. In these individuals, hearing loss is more severe than in people who have mutations in the CDH23 gene but lack the ATP2B2 gene variation. The Val586Met variation in the ATP2B2 gene might also modify hearing loss when it occurs with a mutation in another hearing loss gene called MYO6. Mutations in the CDH23 and MYO6 genes impair the conversion of sound waves to nerve impulses. It remains unclear how the variation in the ATP2B2 gene further impairs hearing loss.