Histone-lysine N-methyltransferase KMT5B (KMT5B)

Histone-lysine N-methyltransferase KMT5B is an enzyme encoded by the KMT5B gene in humans. It catalyzes the dimethylation of lysine 20 on histone H4 (H4K20me2), an important epigenetic modification involved in chromatin compaction, transcriptional repression, and DNA repair[1][2][4][6][7][8]. The enzyme contains a SET domain characteristic of many histone methyltransferases[1][6]. Pathogenic variants in KMT5B cause autosomal dominant neurodevelopmental disorders, including intellectual disability, global developmental delay, autism spectrum disorder, macrocephaly, and muscle disorders[2][4][6]. KMT5B activity is critical for normal neurodevelopment and muscle formation and may play a role in carcinogenesis through its function in chromatin regulation[4][6]. No clinically approved drugs selectively target KMT5B, but general inhibitors of lysine methyltransferases are under preclinical investigation[5]. The primary biological marker of KMT5B activity is the dimethylation state of H4K20, and KMT5B gene variants can serve as genetic biomarkers in rare neurodevelopmental conditions[2][6]. Safety concerns for therapeutic targeting include disruption of essential epigenetic mechanisms and associated developmental defects.

Other names

Lysine methyltransferase 5BSUV4-20H1Suppressor of variegation 4-20 homolog 1

Inhibition of methyltransferase activity (via SAM-competitive inhibition or SET domain inhibition)