Histone-lysine N-methyltransferase 2C (KMT2C)

Histone-lysine N-methyltransferase 2C (KMT2C), also known as MLL3, is a large nuclear enzyme belonging to the mixed-lineage leukemia (MLL) family[2][4][5]. It acts as a key component of chromatin-modifying complexes, specifically catalyzing monomethylation of histone H3 lysine 4 (H3K4me1) at enhancer regions[1][3][4][6]. KMT2C regulates chromatin accessibility, transcriptional activation, and cell fate decisions by establishing and maintaining active enhancer signatures through cooperation with other epigenetic modifiers such as CBP/p300 and UTX[3]. Its biological activities are essential for normal development, differentiation, and DNA damage response, with loss-of-function mutations or reduced expression promoting oncogenic transformation and developmental disorders[1][5]. KMT2C is frequently mutated in human cancers, functioning as a tumor suppressor whose deficiency disrupts enhancer-associated gene regulation, leading to abnormalities in cell proliferation, migration, and immune escape mechanisms[1][3]. Pathogenic mutations also cause Kleefstra syndrome-2, a neurodevelopmental disease[2][4][5]. KMT2C is increasingly studied as a prognostic biomarker and a synthetic lethal therapeutic target, with selective vulnerabilities exposed to certain epigenetic drugs in tumors bearing KMT2C alterations[1][5]. Complete loss of KMT2C is embryonic lethal in mice, highlighting its critical role in chromatin biology and gene regulation[1].

Other names

Myeloid/lymphoid or mixed-lineage leukemia protein 3MLL3Lysine N-methyltransferase 2CALR-like proteinHomologous to ALR proteinHALRKIAA1506KLEFS2

Inhibitors (synthetic lethals targeting epigenetic vulnerabilities; e.g., EZH2 inhibition in the context of KMT2C mutation[1])