COQ2 gene

The COQ2 gene provides instructions for creating an enzyme essential for the production of coenzyme Q10, a molecule critical for cellular energy and protection.

Normal Function

The COQ2 gene provides instructions for making an enzyme that carries out one step in the production of a molecule called coenzyme Q10, which has several critical functions in cells throughout the body. In cell structures called mitochondria, coenzyme Q10 plays an essential role in a process called oxidative phosphorylation, which converts the energy from food into a form cells can use. Coenzyme Q10 is also involved in producing pyrimidines, which are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. In cell membranes, coenzyme Q10 acts as an antioxidant, protecting cells from damage caused by unstable oxygen-containing molecules (free radicals), which are byproducts of energy production.

Health Conditions Related to Genetic Changes

Multiple system atrophy

Several variations in the COQ2 gene have been suggested to increase the risk of multiple system atrophy, a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary, such as regulation of blood pressure.

• The identified variations alter single protein building blocks (amino acids) in the COQ2 enzyme.
• Most variations are rare, but a change replacing valine with alanine at position 393 (Val393Ala or V393A) is relatively common.
• Studies suggest these variations are associated with increased risk in the Japanese population, but this correlation has not been found in Korean, European, or North American populations.
• It remains unclear whether COQ2 gene variations represent a significant risk factor for this disease.

Researchers speculate that these changes may impair COQ2 enzyme activity, reducing coenzyme Q10 levels. While coenzyme Q10 levels are reduced in the brains of people with multiple system atrophy, these specific variations are thought to affect coenzyme Q10 levels less severely than mutations causing primary coenzyme Q10 deficiency.

Primary coenzyme Q10 deficiency

At least nine mutations in the COQ2 gene have been found to cause primary coenzyme Q10 deficiency. This rare disease usually becomes apparent in infancy or early childhood, but it can occur at any age. It can affect many parts of the body, most often the brain, muscles, and kidneys.

• Mutations associated with this disorder greatly reduce or eliminate the production of the COQ2 enzyme.
• A shortage of coenzyme Q10 impairs oxidative phosphorylation and increases cell vulnerability to free radical damage.
• Deficiency may also disrupt the production of pyrimidines, leading to cellular malfunction across various organs and tissues.