Histone-lysine N-methyltransferase SETD1B (SETD1B)

Histone-lysine N-methyltransferase SETD1B (SETD1B) is an epigenetic enzyme belonging to the class V-like SAM-binding methyltransferase superfamily and forms part of the COMPASS complex that catalyzes mono-, di-, and trimethylation of histone H3 at lysine 4 (H3K4). These methylation marks are associated with active chromatin states and transcriptional regulation. SETD1B is essential for proper gene expression during neurodevelopment and in postnatal neurons, notably regulating genes required for synaptic plasticity, memory, and learning. It also plays a role in controlling gene expression in hematopoietic progenitor cells and is critical for oocyte maturation and fertility. Pathogenic variants cause a spectrum of autosomal dominant neurodevelopmental disorders (often with intellectual disability, seizures, and language delay), and impairments in oogenesis leading to female infertility. The widespread involvement of SETD1B in crucial gene regulation programs means that while it is a potential therapeutic target, it may present significant safety and specificity challenges.

Other names

KIAA1076KMT2GSET1BhSET1BLysine N-methyltransferase 2GSET domain-containing protein 1BSet1BIDDSELD

Drugs (if developed) would likely act as inhibitors or modulators of the methyltransferase catalytic site, altering H3K4 methylation and hence gene expression programs