KCNQ1OT1

The KCNQ1OT1 gene is located within another gene, KCNQ1. Because the two genes share a region of overlapping DNA, KCNQ1OT1 is also known as KCNQ1 overlapping transcript 1. The DNA sequence of two genes is "read" in opposite directions, however, and the genes have very different functions. Unlike KCNQ1, which provides instructions for making a protein that acts as a potassium channel, the KCNQ1OT1 gene does not contain instructions for making a protein. Instead, a molecule called a noncoding RNA (a chemical cousin of DNA) is produced from the KCNQ1OT1 gene. This RNA helps regulate genes that are essential for normal growth and development before birth.

People inherit one copy of most genes from their mother and one copy from their father. Both copies are typically active, or "turned on," in cells. The KCNQ1OT1 gene, however, is active only when it is inherited from a person's father. This sort of parent-specific difference in gene activation is caused by a phenomenon called genomic imprinting.

KCNQ1OT1 is part of a cluster of genes on the short (p) arm of chromosome 11 that undergo genomic imprinting. KCNQ1OT1 and several other genes in this cluster are controlled by a nearby region of DNA known as imprinting center 2 (ICR2) or KvDMR. The KCNQ1OT1 gene plays an important role in maintaining the genomic imprinting of these genes. Several of the genes in this cluster are thought to help regulate growth.

Beckwith-Wiedemann syndrome - associated with the KCNQ1OT1 gene

At least half of all cases of Beckwith-Wiedemann result from changes in a process called methylation that affects the ICR2 region. In genes that undergo genomic imprinting, the parent of origin is often marked, or "stamped," on the gene during the formation of egg and sperm cells. This stamping process, called methylation, is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA.

In many people with Beckwith-Wiedemann syndrome, the ICR2 region has too few methyl groups attached (hypomethylation). This abnormality disrupts the regulation of several genes that are normally controlled by ICR2. Specifically, hypomethylation of the ICR2 region leads to an increase in the activity of KCNQ1OT1 and a reduction in the activity of other nearby genes. Because some of these genes are involved in directing growth, a loss of their activity leads to overgrowth, an increased risk of tumors, and the other features of Beckwith-Wiedemann syndrome.

In a few cases, Beckwith-Wiedemann syndrome has been caused by deletions of a small amount of DNA from the ICR2 region. Like abnormal methylation, these deletions disrupt the activity of several genes, including KCNQ1OT1.