• autosomal dominant intellectual developmental disorder

This report describes intellectual disability, autosomal dominant, CAMK2-related, which includes several syndromic forms of intellectual disability associated with genes that encode subunits of calcium/calmodulin-dependent protein kinase II (CaM kinase II, CAMK2). CAMK2 is a ubiquitous serine/threonine protein kinase that is abundant in the brain and has key roles in synaptic plasticity, learning, and memory. A single Drosophila gene, Dmel\CaMKII, is orthologous to four CAMK2 genes in human, two of which are implicated in intellectual disability (MIM:617798, FBhh0000868; MIM:617799, FBhh0000869). Classical loss-of-function mutations, RNAi targeting constructs, alleles caused by insertional mutagenesis, and amorphic alleles created by targeted recombination have been generated for Dmel\CaMKII.

UAS constructs of the human genes Hsap\CAMK2A and Hsap\CAMK2B have been introduced into flies, but have not been characterized in the context of this human disease model.

Loss-of-function mutations of Dmel\CaMKII are typically homozygous lethal. Targeted loss of function effected by RNAi results in learning defects, neurophysiology and neuroanatomy defects; targeted expression of an overactive (calcium independent) allele has also been studied. Many physical and genetic interactions have been described for Dmel\CaMKII (see below and in the gene report for CaMKII), including with the fly gene CASK. The human ortholog of Dmel\CASK has also been implicated in forms intellectual disability; see the human disease model report, 'intellectual disability, X-linked, CASK-related' (FBhh0000867). Work done in flies supports a role of CASK in the regulation of CaMKII autophosphorylation.

[updated Aug. 2018 by FlyBase; FBrf0222196]