Role of calcium/calmodulin-dependent kinase 2 in neurodevelopmental disorders

Brain Res Bull. 2021 Jun:171:209-220. doi: 10.1016/j.brainresbull.2021.03.014. Epub 2021 Mar 24.

Abstract

Neurodevelopmental disorders are a complex and heterogeneous group of neurological disorders characterized by their early-onset and estimated to affect more than 3% of children worldwide. The rapid advancement of sequencing technologies in the past years allowed the identification of hundreds of variants in several different genes causing neurodevelopmental disorders. Between those, new variants in the Calcium/calmodulin dependent protein kinase II (CAMK2) genes were recently linked to intellectual disability. Despite many years of research on CAMK2, this proves for the first time that this well-known and highly conserved molecule plays an important role in the human brain. In this review, we give an overview of the identified CAMK2 variants, and we speculate on potential mechanisms through which dysfunctions in CAMK2 result in neurodevelopmental disorders. Additionally, we discuss how the identification of CAMK2 variants might result in new exciting discoveries regarding the function of CAMK2 in the human brain.

Keywords: CAMK2; Intellectual disability; Plasticity; de novo variants.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Calmodulin / metabolism
  • Humans
  • Neurodevelopmental Disorders / metabolism*
  • Neuronal Plasticity / physiology*
  • Phosphorylation

Substances

  • Calmodulin
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium