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Available structures
PDB Ortholog search: PDBe RCSB
Aliases KMT2D, AAD10, ALR, CAGL114, KABUK1, KMS, MLL2, MLL4, TNRC21, lysine methyltransferase 2D
External IDs MGI: 2682319 HomoloGene: 86893 GeneCards: 8085
RNA expression pattern
PBB GE MLL2 211790 s at tn.png

PBB GE MLL2 216845 x at tn.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 12: 49.02 – 49.06 Mb Chr 15: 98.83 – 98.87 Mb
PubMed search [1] [2]
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Histone-lysine N-methyltransferase 2D (KMT2D) previously known as myeloid/lymphoid or mixed-lineage leukemia protein 2 (MLL2) is an enzyme that in humans is encoded by the KMT2D gene.[3][4] The gene is located on chromosome 12.This is a Trithorax-group protein.


This gene is also generally known as MLL4 in the literature. This nomenclature has caused much confusion in the data bases. Originally MLL2 was used to describe the sister gene of MLL1, which is also a trithorax-group histone methyltransferase.

The MLL1 gene was originally named MLL after myeloid/lymphoid or mixed-lineage leukemia cases. Its closest homologue is a very similar gene (not the gene described here), which is also called MLL2, but sometimes unfortunately called MLL4. The gene described here as MLL2 should properly be called MLL4 because along with its closely related homologue MLL3, it is closely related to a different Drosophila homologue of trithorax. The material included below refers to the trithorax group protein that is associated with MLL3 and a protein complex, not containing menin but including PTIP. It is listed as MLL2 but it should properly be called MLL4. It is now understood that its effect in lymphomagenesis is via the disruption of chromatin regulation.[5]

Clinical significance[edit]

Two thirds of a sample of 53 cases of Kabuki Syndrome have a loss-of-function mutation in the KMT2D gene.[6]

Mutations of this gene are common in various types of B-cell lymphoma [5] and are also associated with medulloblastoma [7] and pheochromocytoma.[8]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Prasad R, Zhadanov AB, Sedkov Y, Bullrich F, Druck T, Rallapalli R, Yano T, Alder H, Croce CM, Huebner K, Mazo A, Canaani E (Aug 1997). "Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax". Oncogene. 15 (5): 549–60. doi:10.1038/sj.onc.1201211. PMID 9247308. 
  4. ^ "Entrez Gene: MLL2 myeloid/lymphoid or mixed-lineage leukemia 2". 
  5. ^ a b Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA (August 2011). "Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma". Nature. 476 (7360): 298–303. doi:10.1038/nature10351. PMC 3210554free to read. PMID 21796119. 
  6. ^ 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 (September 2010). "Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome". Nat. Genet. 42 (9): 790–3. doi:10.1038/ng.646. PMC 2930028free to read. PMID 20711175. 
  7. ^ Jones DT, Jäger N, Kool M, Zichner T, Hutter B, Sultan M, Cho YJ, Pugh TJ, Hovestadt V, Stütz AM, Rausch T, Warnatz HJ, Ryzhova M, Bender S, Sturm D, Pleier S, Cin H, Pfaff E, Sieber L, Wittmann A, Remke M, Witt H, Hutter S, Tzaridis T, Weischenfeldt J, Raeder B, Avci M, Amstislavskiy V, Zapatka M, Weber UD, Wang Q, Lasitschka B, Bartholomae CC, Schmidt M, von Kalle C, Ast V, Lawerenz C, Eils J, Kabbe R, Benes V, van Sluis P, Koster J, Volckmann R, Shih D, Betts MJ, Russell RB, Coco S, Tonini GP, Schüller U, Hans V, Graf N, Kim YJ, Monoranu C, Roggendorf W, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, von Deimling A, Witt O, Maass E, Rössler J, Ebinger M, Schuhmann MU, Frühwald MC, Hasselblatt M, Jabado N, Rutkowski S, von Bueren AO, Williamson D, Clifford SC, McCabe MG, Collins VP, Wolf S, Wiemann S, Lehrach H, Brors B, Scheurlen W, Felsberg J, Reifenberger G, Northcott PA, Taylor MD, Meyerson M, Pomeroy SL, Yaspo ML, Korbel JO, Korshunov A, Eils R, Pfister SM, Lichter P (July 2012). "Dissecting the genomic complexity underlying medulloblastoma". Nature. 488 (7409): 100–5. doi:10.1038/nature11284. PMC 3662966free to read. PMID 22832583. 
  8. ^ Juhlin CC, Stenman A, Haglund F, Clark VE, Brown TC, Baranoski J, Bilguvar K, Goh G, Welander J, Svahn F, Rubinstein JC, Caramuta S, Yasuno K, Günel M, Bäckdahl M, Gimm O, Söderkvist P, Prasad ML, Korah R, Lifton RP, Carling T (May 2015). "Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene". Genes Chromosomes Cancer. 54 (9): 542–54. doi:10.1002/gcc.22267. PMID 26032282. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.