The CC2D1A gene contains 31 exons and spans 37 kb. It is mapped to chromosome 19p13.12. At embryonic day 16, expression was strongest in the cortical plate; from postnatal day 3 to adulthood, expression was strongest in the cerebral cortex and hippocampus, especially in the CA3 region of the hippocampal. CC2D1A is a transcriptional repressor; there is evidence for its role in several cellular signaling pathways, including nuclear factor-κB (NF-κB) and protein kinase B (PKB). CC2D1A is abundantly detected in the brain (especially in the cerebral cortex, hippocampus, basal ganglia, and hypothalamus). The physiological role of the CC2D1A gene is not entirely known. Loss of function of the CC2D1A gene appears to only affect the brain, leading to a range of behavioral problems in humans. Disruption of this gene affects many biochemical pathways including cAMP response element-binding protein (CREB), NF-κB, protein kinase A (PKA), protein kinase B (PKB/AKT), Notch and the BMP. This gene plays a role in the transcriptional regulation of dopamine and serotonin receptors in the brain. The CC2D1A gene functions to bind DNA and suppress transcription of the serotonin receptor 1 A (HTR1A).
To date several mutations have been identified including missense, frameshift, IVS, splicing, multi exon deletion with the classification of pathogenic (P), likely pathogenic (LP) and uncertain significance (VUS). These are either homozygous and heterozygous mutations or compound heterozygotes.
These mutations can be identified via molecular genetic testing either by directly examining CC2D1A or via whole genome/exome sequencing.
Deletion of Cc2d1a (mice) results in a reduction in dendritic complexity and number of dendritic spines. Cc2d1a-deficient mice develop normally in utero, but die immediately after birth due to respiratory and swallowing deficit. Cc2d1a conditional knock-out mice exhibit learning and memory deficits, hyperactivity, anxiety, social deficits and repetitive behaviors that are core features of autism and ID.
CC2D1A