MLL2

KMT2D
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases KMT2D, AAD10, ALR, CAGL114, KABUK1, KMS, MLL2, MLL4, TNRC21, lysine methyltransferase 2D
External IDs MGI: 2682319 HomoloGene: 86893 GeneCards: KMT2D
RNA expression pattern


More reference expression data
Orthologs
Species Human Mouse
Entrez

8085

381022

Ensembl

ENSG00000167548

ENSMUSG00000048154

UniProt

O14686

Q6PDK2

RefSeq (mRNA)

NM_003482

NM_001033276
NM_001033388

RefSeq (protein)

NP_003473.3

n/a

Location (UCSC) Chr 12: 49.02 – 49.06 Mb Chr 15: 98.83 – 98.87 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

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.

Nomenclature

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

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]

References

  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. 1 2 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 3210554Freely accessible. 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 2930028Freely accessible. 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 3662966Freely accessible. 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

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


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