ANK2

The ANK2 gene provides instructions for making a protein called ankyrin-2. Ankyrin-2 is part of a larger family of ankyrins, which interact with many other types of proteins in cells throughout the body. Ankyrins ensure that certain proteins are inserted into the correct locations in the cell membrane and are anchored to the cell's structural framework (the cytoskeleton). Ankyrins play key roles in important cellular functions including movement, growth, and division.

The ankyrin-2 protein is active in many cell types, particularly in the brain and in heart (cardiac) muscle. This protein mainly targets ion channels, which are complexes of proteins that transport charged atoms (ions) across cell membranes. In the heart, the flow of ions (such as sodium, potassium, and calcium) through ion channels is critical for signaling the heart to beat and for maintaining a normal heart rhythm. Ankyrin-2 inserts these channels into their proper locations in the cell membrane so they can regulate the flow of ions into and out of cardiac muscle cells.

Romano-Ward syndrome - associated with the ANK2 gene

At least 10 mutations in the ANK2 gene have been associated with a variety of heart problems. It is unclear whether these mutations cause Romano-Ward syndrome or lead to another heart condition with some of the same signs and symptoms. Most often, mutations in the ANK2 gene lead to abnormalities of the heart's natural pacemaker (the sinoatrial node), a heart rate that is slower than normal (bradycardia), a disruption in the rhythm of the heart's lower chambers (ventricular arrhythmia), and an increased risk of fainting (syncope) and sudden death. Other symptoms, including seizures, dizziness, and migraine headaches, also have been reported in people with ANK2 mutations.

Each of the identified mutations in the ANK2 gene changes a single protein building block (amino acid) in a critical region of the ankyrin-2 protein. As a result, the altered protein cannot target ion channels to their correct locations in cardiac muscle cells or other types of cells. Although the channels are produced normally by the cell, they are unable to function if they are not inserted correctly into the cell membrane. This loss of functional channels in the heart disrupts the normal flow of ions, which alters the heart's normal rhythm and probably interferes with other aspects of cardiac function.