KCNH2

The KCNH2 gene belongs to a large family of genes that provide instructions for making potassium channels. These channels, which transport positively charged atoms (ions) of potassium into and out of cells, play a key role in a cell's ability to generate and transmit electrical signals.

The specific function of a potassium channel depends on its protein components and its location in the body. Channels made with the KCNH2 protein are active in heart (cardiac) muscle, where they transport potassium ions out of cells. This form of ion transport is involved in recharging the cardiac muscle after each heartbeat to maintain a regular rhythm. The KCNH2 protein is also produced in nerve cells and certain immune cells (microglia) in the central nervous system.

The proteins produced from the KCNH2 gene and another gene, KCNE2, interact to form a functional potassium channel. Four alpha subunits, each produced from the KCNH2 gene, form the structure of each channel. One beta subunit, produced from the KCNE2 gene, binds to the channel and regulates its activity.

Romano-Ward syndrome - caused by mutations in the KCNH2 gene

Mutations in the KCNH2 gene are a common cause of Romano-Ward syndrome. More than 140 disorder-causing mutations have been identified. Some of these mutations change a single protein building block (amino acid) in the KCNH2 protein, while other mutations delete several amino acids from the protein. These changes prevent the protein from assembling into functional ion channels or alter the channels' structure and function. As a result, the channels cannot properly regulate the flow of potassium ions in cardiac muscle cells. A disruption in ion transport leads to an irregular heartbeat (arrhythmia) that increases the risk of fainting (syncope) and sudden death.

short QT syndrome - caused by mutations in the KCNH2 gene

Mutations in the KCNH2 gene are also associated with a heart condition called short QT syndrome. In a small number of families with this condition, researchers have identified a mutation that replaces the amino acid asparagine with the amino acid lysine at position 588 of the KCNH2 protein (written as Asn588Lys or N588K). This switch in amino acids disrupts the usual function of ion channels made with the KCNH2 protein, increasing the channels' activity. By allowing more potassium ions to flow out of cardiac muscle cells at a critical time during the heartbeat, the N588K mutation is likely responsible for the changes in heart rhythm found in short QT syndrome.

other disorders - associated with the KCNH2 gene

Certain drugs, including medications used to treat arrhythmias, infections, seizures, and psychotic disorders, can lead to an abnormal heart rhythm in some people. This drug-induced heart condition, which is known as acquired long QT syndrome, increases the risk of cardiac arrest and sudden death. A small percentage of cases of acquired long QT syndrome occur in people who have an underlying mutation in the KCNH2 gene.