KCNQ1 gene

potassium voltage-gated channel subfamily Q member 1

The KCNQ1 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 KCNQ1 protein are active in the inner ear and in heart (cardiac) muscle. In the inner ear, these channels help maintain the proper ion balance needed for normal hearing. In the heart, the channels are involved in recharging the cardiac muscle after each heartbeat to maintain a regular rhythm. The KCNQ1 protein is also produced in the kidney, lung, stomach, and intestine, where it is involved in transporting molecules across cell membranes.

The KCNQ1 protein interacts with proteins in the KCNE family (such as the KCNE1 protein) to form functional potassium channels. Four alpha subunits made from the KCNQ1 protein form the structure of each channel. One beta subunit, made from a KCNE protein, attaches (binds) to the channel and regulates its activity.

Changes in the KCNQ1 gene are an uncommon cause of familial atrial fibrillation, a disruption of the heart's normal rhythm (arrhythmia) characterized by uncoordinated electrical activity in the heart's upper chambers (the atria). Several mutations have been found to cause the condition; these genetic changes alter single protein building blocks (amino acids) in the KCNQ1 protein. In cardiac muscle cells, the mutations appear to increase the flow of potassium ions through the channel formed with the KCNQ1 protein. The enhanced ion transport can disrupt the heart's normal rhythm, resulting in atrial fibrillation.

At least 16 KCNQ1 gene mutations have been found to cause Jervell and Lange-Nielsen syndrome, a condition that causes arrhythmia and profound hearing loss from birth. These mutations are typically present in both copies of the KCNQ1 gene in each cell. Most of these changes lead to the production of an abnormally short, nonfunctional version of the KCNQ1 protein that cannot be used to build potassium channels. Other mutations change a small number of amino acids in this protein, which alters the normal structure and function of the channels. An inability of these channels to properly transport potassium ions in the inner ear and cardiac muscle leads to the hearing loss and arrhythmia characteristic of Jervell and Lange-Nielsen syndrome.

Changes in the KCNQ1 gene are thought to be the most 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 arrhythmia.

More than 500 KCNQ1 gene mutations that cause Romano-Ward syndrome have been identified. Unlike the mutations associated with Jervell and Lange-Nielsen syndrome, the mutations that cause Romano-Ward syndrome are typically present in only one copy of the KCNQ1 gene in each cell. Most of these mutations change single amino acids in the KCNQ1 protein or insert or delete a small number of amino acids. These changes allow the protein to form channels but reduce the channels' ability to transport potassium ions out of 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.

At least one mutation in the KCNQ1 gene can 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.

The KCNQ1 gene mutation associated with short QT syndrome replaces the amino acid valine with the amino acid leucine at protein position 307 (written as Val307Leu or V307L). The mutation alters the function of ion channels made with the KCNQ1 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.

Mutations in the KCNQ1 gene have been associated with several other conditions related to heart rhythm abnormalities, including sudden infant death syndrome (SIDS) and acquired long QT syndrome.

SIDS is a major cause of death in babies younger than one year. It is characterized by sudden and unexplained death, usually during sleep. Although the cause of SIDS is often unknown, researchers have identified mutations in the KCNQ1 gene in a few cases of this condition. Other genetic and environmental factors, many of which have not been identified, also play a part in determining the risk of SIDS.

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 KCNQ1 gene.

Cytogenetic Location: 11p15.5-p15.4, which is the short (p) arm of chromosome 11 between positions 15.5 and 15.4

Molecular Location: base pairs 2,444,991 to 2,849,110 on chromosome 11 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 11p15.5-p15.4, which is the short (p) arm of chromosome 11 between positions 15.5 and 15.4
  • ATFB1
  • IKs producing slow voltage-gated potassium channel alpha subunit KvLQT1
  • JLNS1
  • KCNA8
  • KCNA9
  • KQT-like 1
  • Kv1.9
  • Kv7.1
  • KVLQT1
  • LQT1
  • potassium channel, voltage gated KQT-like subfamily Q, member 1
  • potassium voltage-gated channel, KQT-like subfamily, member 1