KCNH2 gene

potassium voltage-gated channel subfamily H member 2

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 out of cells, play key roles 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 (also known as hERG1) are active in heart (cardiac) muscle. They are 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, attaches (binds) to the channel and regulates its activity.

Mutations in the KCNH2 gene are a common cause of Romano-Ward syndrome, often called long QT syndrome. This condition causes the heart (cardiac) muscle to take longer than usual to recharge between beats, which can lead to an abnormal heart rhythm (arrhythmia).

More than 500 KCNH2 gene mutations that cause Romano-Ward syndrome 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. As a result, the channels cannot properly regulate the flow of potassium ions in cardiac muscle cells. The reduced ion transport alters the transmission of electrical signals in the heart, increasing the risk of an irregular heartbeat that can cause fainting (syncope) or sudden death.

Mutations in the KCNH2 gene can also cause a heart condition called short QT syndrome. In people with this condition, the cardiac muscle takes less time than usual to recharge between beats. This change increases the risk of an abnormal heart rhythm that can cause syncope or sudden death.

At least two mutations in the KCNH2 gene have been found to cause short QT syndrome in a small number of affected families. These mutations change single amino acids in the KCNH2 protein. The genetic changes alter the function of ion channels made with the KCNH2 protein, increasing the channels' activity. As a result, more potassium ions flow out of cardiac muscle cells at a critical time during the heartbeat, which can lead to an irregular heart rhythm.

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 variation in the KCNH2 gene.

Cytogenetic Location: 7q36.1, which is the long (q) arm of chromosome 7 at position 36.1

Molecular Location: base pairs 150,944,956 to 150,978,314 on chromosome 7 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 7q36.1, which is the long (q) arm of chromosome 7 at position 36.1
  • Eag related protein 1
  • ERG1
  • Ether-a-go-go related gene potassium channel 1
  • HERG
  • HERG1
  • human ether a-go-go-related gene
  • KCNH2_HUMAN
  • Kv11.1
  • LQT2
  • potassium channel, voltage gated eag related subfamily H, member 2
  • potassium voltage-gated channel, subfamily H (eag-related), member 2