Pathogenic KDM5B variants in the context of developmental disorders

Biochim Biophys Acta Gene Regul Mech. 2022 Jul;1865(5):194848. doi: 10.1016/j.bbagrm.2022.194848. Epub 2022 Jul 26.

Abstract

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.

Keywords: Developmental disorders; Epigenetics; Histone modifying enzymes; KDM5B.

Publication types

  • Review

MeSH terms

  • Child
  • Developmental Disabilities / genetics
  • Histones* / genetics
  • Histones* / metabolism
  • Humans
  • Jumonji Domain-Containing Histone Demethylases* / genetics
  • Jumonji Domain-Containing Histone Demethylases* / metabolism
  • Nuclear Proteins / metabolism
  • Repressor Proteins / metabolism

Substances

  • Histones
  • Nuclear Proteins
  • Repressor Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • KDM5B protein, human