A de novo non-coding variant that was predicted to target the CDK5RAP2 gene via chromatin interactions was identified in a Korean ASD proband from a simplex family in Kim et al., 2022; functional analysis in human induced pluripotent stem cells derived from the proband and the proband's parents demonstrated that this variant resulted in significantly reduced levels of CDK5RAP2 expression in patient-derived hiPSCs compared to parent-derived hiPSCs. Multiple rare de novo non-coding variants in CDK5RAP2 have also been identified in ASD probands from the Simons Simplex Collection, the Autism Sequencing Consortium, and the MSSNG cohort (De Rubeis et al., 2014; Turner et al., 2016; Yuen et al., 2016; Yuen et al., 2017; Turner et al., 2017; Satterstrom et al., 2020), while sequencing of 136 microcephaly or macrocephaly-related genes and 158 possible ASD risk genes in 536 Chinese ASD probands in Li et al., 2017 identified a potentially damaging missense variant in this gene in an ASD proband.
Molecular Function
This gene encodes a regulator of CDK5 (cyclin-dependent kinase 5) activity. The protein encoded by this gene is localized to the centrosome and Golgi complex, interacts with CDK5R1 and pericentrin (PCNT), plays a role in centriole engagement and microtubule nucleation, and has been linked to primary microcephaly and Alzheimer's disease. Biallelic mutations in this gene are responsible for an autosomal recessive form of primary microcephaly (MCPH3; OMIM 604804) (Bond et al., 2005; Pagnamenta et al., 2012; Lancaster et al., 2013; Tan et al., 2014; Pagnamenta et al., 2016).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Non-coding de novo mutations in chromatin interactions are implicated in autism spectrum disorder
