Pathogenic KDM5B variants in the context of developmental disorders

• Published in: Biochimica et biophysica acta. Gene regulatory mechanisms 2022-07, Vol.1865 (5), p.194848-194848, Article 194848
• Main Authors: Harrington, Jack, Wheway, Gabrielle, Willaime-Morawek, Sandrine, Gibson, Jane, Walters, Zoë S.
• Format: Article
• Language: English
• Subjects: Developmental disorders; Epigenetics; Histone modifying enzymes; KDM5B
• ISSN: 1874-9399; 1876-4320
• DOI: 10.1016/j.bbagrm.2022.194848

Histone modifying enzymes are involved in the posttranslational modification of histones and the epigenetic control of gene expression. They play a critical role in normal development, and there is increasing evidence of their role in developmental disorders (DDs). DDs are a group of chronic, severe conditions that impact the physical, intellectual, language and/or behavioral development of an individual. There are very few treatment options available for DDs such that these are conditions with significant unmet clinical need. Recessive variants in the gene encoding histone modifying enzyme KDM5B are associated with a DD characterized by developmental delay, facial dysmorphism and camptodactyly. KDM5B is responsible for the demethylation of lysine 4 on the amino tail of histone 3 and plays a vital role in normal development and regulating cell differentiation. This review explores the literature on KDM5B and what is currently known about its roles in development and developmental disorders. •KDM5B is a histone modifying enzyme responsible for the demethylation of H3K4.•Its gene regulatory functions play a vital role in normal embryonic development.•KDM5B is implicated in the pathogenesis of diseases including developmental disorders.•Model systems including disease models have been pivotal in exploring KDM5B function.•Exploring molecular mechanisms of KDM5B function reveals novel therapeutic avenues.