Nuclear receptor-binding SET domain protein 1 (NSD1)

Nuclear receptor-binding SET domain protein 1 (NSD1) is a large, multi-domain histone methyltransferase that catalyzes the mono- and di-methylation of lysine 36 on histone H3 (H3K36), and may also act on histone H4 at lysine 20. Containing a catalytic SET domain, PWWP domains, PHD fingers, and interaction motifs for nuclear receptors, NSD1 is a critical chromatin regulator involved in transcriptional activation and repression. It regulates gene expression during embryonic development and controls growth, and is implicated in multiple diseases when mutated or dysregulated. NSD1 loss-of-function causes Sotos syndrome, a childhood overgrowth disorder, while chromosomal rearrangements involving NSD1 are oncogenic in acute myeloid leukemia and other cancers. NSD1 acts both as a tumor suppressor and oncogene, depending on cellular context, and is an emerging epigenetic target in oncology research.

Other names

Histone-lysine N-methyltransferase, H3 lysine-36 specificLysine N-methyltransferase 3BKMT3BARA267Nuclear receptor SET domain-containing protein 1Androgen receptor coactivator 267 kDa proteinSOTOSSOTOS1

Drugs targeting NSD1 (if developed) would likely act as histone methyltransferase inhibitors, blocking methylation of H3K36 to influence gene expression and chromatin state.