KMT2D

The KMT2D gene provides instructions for making a protein that is found in many organs and tissues of the body.

The KMT2D protein functions as a histone methyltransferase. Histone methyltransferases are enzymes that modify proteins called histones. Histones are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones, histone methyltransferases control (regulate) the activity of certain genes, which is essential for normal development and function. The histone methyltransferase produced from the KMT2D gene appears to activate certain genes that are important for development.

The KMT2D protein is also believed to act as a tumor suppressor, which means it normally helps prevent cells from growing and dividing in an uncontrolled way.

Kabuki syndrome - caused by mutations in the KMT2D gene

More than 30 mutations in the KMT2D gene have been identified in people with Kabuki syndrome, a disorder characterized by distinctive facial features, intellectual disability, and abnormalities affecting other parts of the body.

The KMT2D gene mutations associated with Kabuki syndrome change one protein building block (amino acid) in the KMT2D protein or result in a premature stop signal that leads to an abnormally short protein. As a result of these mutations, the KMT2D protein is nonfunctional. A lack of functional KMT2D protein disrupts its role in histone methylation and impairs proper activation of certain genes in many of the body's organs and tissues, resulting in the abnormalities of development and function characteristic of Kabuki syndrome.

Although the KMT2D protein is a tumor suppressor, a loss of this protein's function does not seem to increase cancer risk in people with Kabuki syndrome.

cancers - associated with the KMT2D gene

Increased amounts of the KMT2D protein and altered distribution of the protein within cells have been identified in cancerous tumors of the breast and colon. It is unknown whether these changes result primarily from increased activity (overexpression) of the KMT2D gene, extra copies of the gene in tumor cells, altered stability or processing of the protein, or other mechanisms. Excess amounts of the KMT2D protein may disrupt the regulation of other genes. As a result, cells may grow and divide too quickly or in an uncontrolled way, leading to cancer.

Some gene mutations occur during a person's lifetime. Such mutations, which are called somatic mutations, are present only in certain cells. Somatic mutations in the KMT2D gene have been identified in medulloblastomas, which are cancerous brain tumors that occur in childhood. Most of these mutations result in an abnormally short, nonfunctional KMT2D protein that cannot perform its role as a tumor suppressor, resulting in the development of cancer.