KMT2A Gene

The KMT2A gene (lysine methyltransferase 2A) encodes a transcriptional coactivator located on chromosome 11q23.3.

The protein encoded by the KMT2A gene plays an essential role in regulating gene expression during early development and hematopoiesis. It contains several conserved functional domains. One of these domains, the SET domain, is responsible for histone H3 lysine 4 (H3K4) methyltransferase activity, which mediates chromatin modifications associated with epigenetic transcriptional activation.

Histone methyltransferase plays an essential role in early development and hematopoiesis. Promotes PPP1R15A-induced apoptosis. Plays a critical role in controlling circadian gene expression and is essential for transcriptional activation mediated by the CLOCK-ARNTL/BMAL1 heterodimer. Provides a permissive chromatin state for circadian transcription by mediating rhythmic methylation of "Lys-4" of histone H3 (H3K4me).

The transcriptional coactivator KMT2A is cleaved by the enzyme Taspase 1 into two fragments: MLL-C and MLL-N. These fragments reassociate and assemble into various multiprotein complexes that regulate the transcription of specific target genes, including many HOX genes.

Several chromosomal translocations involving this gene are the cause of certain forms of acute lymphoblastic leukemias (Panagopoulos I et al. 2021) and acute myeloid leukemias (AML).

Diseases associated with KMT2A include:

• Wiedemann-Steiner syndrome
• and
• acute myeloid leukemia.

1. Beighton PH (1970) Familial hypertrichosis cubiti: hairy elbows syndrome. J Med Genet 7 158-160.
2. Edwards MJ et al (1994) Hypertrichosis 'cubiti' with facial asymmetry. Am J Med Genet 53: 56-58.
3. Flannery DB et al (1989) Hypertrichosis cubiti. Am J Med Genet 32: 482-483.
4. Jones WD et al (2012) De novo mutations in MLL cause Wiedemann-Steiner syndrome. Am J Hum Genet 91: 358-364.
5. Koc A et al (2007) A new case of hairy elbows syndrome (hypertrichosis cubiti). Genet. Counsel. 18: 325-330
6. Koenig, R., Meinecke, P., Kuechler, A., Schafer, D., Muller, D. Wiedemann-Steiner syndrome: three further cases. Am. J. Med. Genet. 152A: 2372-2375, 2010. [PubMed: 20803650, related citations] [Full Text].
7. Luo S et al (2021) Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann-Steiner syndrome. Mol Genet Genomic Med 9:e1798.
8. MacDermot, K. D., Patton, M. A., Williams, M. J. H., Winter, R. M. Hypertrichosis cubiti (hairy elbows) and short stature: a recognizable association. J. Med. Genet. 26: 382-385, 1989. [PubMed: 2738900, related citations] [Full Text].
9. Miyake N et al (2016) Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations. Clin Genet 89: 115-119.
10. Panagopoulos I et al (2021) Rare KMT2A-ELL and Novel ZNF56-KMT2A Fusion Genes in Pediatric T-cell Acute Lymphoblastic Leukemia. Cancer Genomics Proteomics 18:121-131.
11. Polizzi A et al (2005) Hypertrichosis cubiti (hairy elbow syndrome): a clue to a malformation syndrome. J Pediat Endocr Metab 18: 1019-1025.
12. Sorge G et al. (2002) The hairy elbows syndrome: report of a case with a particularly severe phenotype. Ital J Pediat 28: 322-325.
13. Wiedemann HR et al (1989) A syndrome of abnormal facies, short stature, and psychomotor retardation. :In: Atlas of Clinical Syndromes: A Visual Aid to Diagnosis for Clinicians and Practicing Physicians. (2nd ed.) London: Wolfe Publishing Ltd. (pub.):198-199.