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 variants (also known as 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 variants 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 changes, 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
MedlinePlus Genetics provides information about Bladder cancerMore About This Health Condition
MedlinePlus Genetics provides information about ColobomaMore About This Health Condition
Some gene variants occur during a person's lifetime. Such changes, which are called somatic variants, are present only in certain cells. Somatic variants 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 variants 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
- Bogershausen N, Wollnik B. Unmasking Kabuki syndrome. Clin Genet. 2013 Mar;83(3):201-11. doi: 10.1111/cge.12051. Epub 2012 Nov 26. Citation on PubMed
- Dentici ML, Di Pede A, Lepri FR, Gnazzo M, Lombardi MH, Auriti C, Petrocchi S, Pisaneschi E, Bellacchio E, Capolino R, Braguglia A, Angioni A, Dotta A, Digilio MC, Dallapiccola B. Kabuki syndrome: clinical and molecular diagnosis in the first year of life. Arch Dis Child. 2015 Feb;100(2):158-64. doi: 10.1136/archdischild-2013-305858. Epub 2014 Oct 3. Citation on PubMed
- Liu S, Hong X, Shen C, Shi Q, Wang J, Xiong F, Qiu Z. Kabuki syndrome: a Chinese case series and systematic review of the spectrum of mutations. BMC Med Genet. 2015 Apr 21;16:26. doi: 10.1186/s12881-015-0171-4. Citation on PubMed or Free article on PubMed Central
- Micale L, Augello B, Maffeo C, Selicorni A, Zucchetti F, Fusco C, De Nittis P, Pellico MT, Mandriani B, Fischetto R, Boccone L, Silengo M, Biamino E, Perria C, Sotgiu S, Serra G, Lapi E, Neri M, Ferlini A, Cavaliere ML, Chiurazzi P, Monica MD, Scarano G, Faravelli F, Ferrari P, Mazzanti L, Pilotta A, Patricelli MG, Bedeschi MF, Benedicenti F, Prontera P, Toschi B, Salviati L, Melis D, Di Battista E, Vancini A, Garavelli L, Zelante L, Merla G. Molecular analysis, pathogenic mechanisms, and readthrough therapy on a large cohort of Kabuki syndrome patients. Hum Mutat. 2014 Jul;35(7):841-50. doi: 10.1002/humu.22547. Epub 2014 Apr 9. Citation on PubMed or Free article on PubMed Central
- Natarajan TG, Kallakury BV, Sheehan CE, Bartlett MB, Ganesan N, Preet A, Ross JS, FitzGerald KT. Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon. Cancer Cell Int. 2010 Apr 30;10:13. doi: 10.1186/1475-2867-10-13. Citation on PubMed or Free article on PubMed Central
- Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet. 2010 Sep;42(9):790-3. doi: 10.1038/ng.646. Epub 2010 Aug 15. Citation on PubMed or Free article on PubMed Central
- Parsons DW, Li M, Zhang X, Jones S, Leary RJ, Lin JC, Boca SM, Carter H, Samayoa J, Bettegowda C, Gallia GL, Jallo GI, Binder ZA, Nikolsky Y, Hartigan J, Smith DR, Gerhard DS, Fults DW, VandenBerg S, Berger MS, Marie SK, Shinjo SM, Clara C, Phillips PC, Minturn JE, Biegel JA, Judkins AR, Resnick AC, Storm PB, Curran T, He Y, Rasheed BA, Friedman HS, Keir ST, McLendon R, Northcott PA, Taylor MD, Burger PC, Riggins GJ, Karchin R, Parmigiani G, Bigner DD, Yan H, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The genetic landscape of the childhood cancer medulloblastoma. Science. 2011 Jan 28;331(6016):435-9. doi: 10.1126/science.1198056. Epub 2010 Dec 16. Citation on PubMed or Free article on PubMed Central
- Paulussen AD, Stegmann AP, Blok MJ, Tserpelis D, Posma-Velter C, Detisch Y, Smeets EE, Wagemans A, Schrander JJ, van den Boogaard MJ, van der Smagt J, van Haeringen A, Stolte-Dijkstra I, Kerstjens-Frederikse WS, Mancini GM, Wessels MW, Hennekam RC, Vreeburg M, Geraedts J, de Ravel T, Fryns JP, Smeets HJ, Devriendt K, Schrander-Stumpel CT. MLL2 mutation spectrum in 45 patients with Kabuki syndrome. Hum Mutat. 2011 Feb;32(2):E2018-25. doi: 10.1002/humu.21416. Epub 2010 Dec 7. Citation on PubMed