KMT2D

KMT2D
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3UVK, 4ERQ, 4Z4P
Identifiers
Aliases	KMT2D, ALR, KABUK1, MLL2, MLL4, lysine methyltransferase 2D, histone-lysine methyltransferase 2D, TNRC21, AAD10, KMS, CAGL114
External IDs	OMIM: 602113; MGI: 2682319; HomoloGene: 86893; GeneCards: KMT2D; OMA:KMT2D - orthologs
Gene location (Human)
Chr.	Chromosome 12 (human)
End	49,060,794 bp
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)
End	98,769,085 bp
RNA expression pattern
	Top expressed in
	buccal mucosa cell; ; internal globus pallidus; ; sural nerve; ; tendon of biceps brachii; ; granulocyte; ; cardia; ; right uterine tube; ; gastrocnemius muscle; ; right hemisphere of cerebellum; ; left uterine tube;
	Top expressed in
	zygote; ; neural layer of retina; ; secondary oocyte; ; granulocyte; ; tail of embryo; ; muscle of thigh; ; superior frontal gyrus; ; primary visual cortex; ; lip; ; ventricular zone;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	metal ion binding; transferase activity; DNA binding; methyltransferase activity; protein binding; histone-lysine N-methyltransferase activity; histone methyltransferase activity (H3-K4 specific); DNA-binding transcription factor activity, RNA polymerase II-specific; transcription coactivator activity; histone binding;
Cellular component	nucleoplasm; MLL3/4 complex; nucleus; histone methyltransferase complex;
Biological process	positive regulation of intracellular estrogen receptor signaling pathway; transcription, DNA-templated; methylation; positive regulation of cell population proliferation; oogenesis; oocyte growth; response to estrogen; positive regulation of transcription by RNA polymerase II; histone H3-K4 methylation; regulation of transcription, DNA-templated; beta-catenin-TCF complex assembly; regulation of megakaryocyte differentiation; chromatin organization;
	Sources:Amigo / QuickGO
Orthologs
	8085
	381022
	ENSG00000167548
	ENSMUSG00000048154
	O14686
	Q6PDK2
	NM_003482
	NM_001033276; NM_001033388
	NP_003473
	NP_001028448
	Wikidata
View/Edit Human	View/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.^[5]^[6] 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.^[7]

Clinical significance

Two thirds of a sample of 53 cases of Kabuki Syndrome have a loss-of-function mutation in the KMT2D gene.^[8]

Mutations of this gene are common in various types of B-cell lymphoma ^[7] and are also associated with medulloblastoma ^[9] and pheochromocytoma.^[10]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000167548 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000048154 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ "Entrez Gene: MLL2 myeloid/lymphoid or mixed-lineage leukemia 2".
^ ^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 3210554. PMID 21796119.
^ 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 2930028. PMID 20711175.
^ 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 3662966. PMID 22832583.
^ 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.

External links

GeneReviews/NCBI/NIH/UW entry on Kabuki syndrome, Kabuki Make-Up Syndrome, Niikawa-Kuroki Syndrome
MLL2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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

This article on a gene on human chromosome 12 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000167548 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000048154 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9247308-5] 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.

[entrez-6] "Entrez Gene: MLL2 myeloid/lymphoid or mixed-lineage leukemia 2".

[pmid21796119-7] 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 3210554. PMID 21796119.

[pmid20711175-8] 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 2930028. PMID 20711175.

[9] 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 3662966. PMID 22832583.

[10] 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.

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Nomenclature

Clinical significance

References

Further reading

External links