A de novo missense variant with an MPC score > 2 was identified in the CYFIP2 gene in a Korean ASD proband in Kim et al., 2024; this gene was subsequently classified as an ASD candidate gene in males following a combined TADA analysis consisting of the Korean ASD cohort described in Kim et al., 2024 in addition to the Simons Simplex Collection and the SPARK cohort. A de novo loss-of-function variant and seven de novo missense variants, including three missense variants with MPC scores>2, were previously identified in the CYFIP2 gene in ASD probands from the Autism Sequencing Consortium and the SPARK cohort (Satterstrom et al., 2020; Zhou et al., 2022; Fu et al., 2022; Trost et al., 2022). Heterozygous variants in CYFIP2 are also responsible for developmental and epileptic encephalopathy-65 (DEE65; OMIM 618008); Zweier et al., 2019 reported that, of the 12 individuals with de novo CYFIP2 variants who presented with developmental delay/intellectual disability and epilepsy in their cohort, one also presented with autism spectrum disorder while another presented with autistic features. Han et al., 2015 found that Cyfip2(+/-) mice exhibited behavioral phenotypes similar to Fmr1-null (Fmr1(-/y)) mice, an animal model of Fragile X syndrome.
Molecular Function
Predicted to enable small GTPase binding activity. Involved in several processes, including activation of cysteine-type endopeptidase activity; cell-cell adhesion; and regulation of postsynapse assembly. Located in perinuclear region of cytoplasm and synapse. Part of SCAR complex. Implicated in developmental and epileptic encephalopathy 65.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Whole genome sequencing analysis identifies sex differences of familial pattern contributing to phenotypic diversity in autism
