The KMT2D gene, also known as MLL2, provides instructions for making an enzyme called lysine-specific methyltransferase 2D that is found in many organs and tissues of the body. Lysine-specific methyltransferase 2D 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 (a process called methylation), histone methyltransferases control (regulate) the activity of certain genes. Lysine-specific methyltransferase 2D appears to activate certain genes that are important for development.
Lysine-specific methyltransferase 2D is also believed to act as a tumor suppressor, which means it normally helps prevent cells from growing and dividing in an uncontrolled way.
Health Conditions Related to Genetic Changes
Hundreds of 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 building block (amino acid) in the lysine-specific methyltransferase 2D enzyme, delete genetic material in the KMT2D gene sequence, or result in a premature stop signal that leads to an abnormally short enzyme. As a result of these mutations, the enzyme is nonfunctional. A lack of functional lysine-specific methyltransferase 2D enzyme 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 lysine-specific methyltransferase 2D is believed to be a tumor suppressor, a loss of this enzyme's function does not seem to increase cancer risk in people with Kabuki syndrome.More About This Health Condition
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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 certain cancers. These include medulloblastomas, which are cancerous brain tumors that occur in childhood, and blood-related cancers called lymphomas. Most of these mutations result in an abnormally short, nonfunctional lysine-specific methyltransferase 2D enzyme that cannot perform its role as a tumor suppressor, resulting in the development of cancer.
Increased amounts of lysine-specific methyltransferase 2D and altered distribution of the enzyme 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 enzyme, or other mechanisms. Excess amounts of lysine-specific methyltransferase 2D 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.
Other Names for This Gene
- ALL1-related protein
- histone-lysine N-methyltransferase MLL2
- lysine (K)-specific methyltransferase 2D
- lysine N-methyltransferase 2B
- myeloid/lymphoid or mixed-lineage leukemia 2
- trinucleotide repeat containing 21
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
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