A de novo missense variant in the KLHL20 gene was identified in an ASD proband from the Autism Sequencing Consortium in Satterstrom et al., 2020. Sleyp et al., 2022 described 14 patients with de novo missense variants in the KLHL20 gene presenting with a neurodevelopmental syndrome characterized by intellectual disability, febrile seizures or epilepsy, autism spectrum disorder or autistic features, hyperactivity, and subtle dysmorphic facial features; a recurrent de novo missense variant (NM_014458.4:c.1069G>A;p.Gly357Arg) was observed in 11 patients.
Molecular Function
The protein encoded by this gene is a substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20) E3 ubiquitin ligase complex mediates the ubiquitination of DAPK1, leading to its degradation by the proteasome, thereby acting as a negative regulator of apoptosis (Lee et al., 2010). The BCR(KLHL20) E3 ubiquitin ligase complex also acts as a regulator of neurite outgrowth by mediating ubiquitination and degradation of PDZ-RhoGEF/ARHGEF11 (Lin et al., 2011).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
De novo missense variants in the E3 ubiquitin ligase adaptor KLHL20 cause a developmental disorder with intellectual disability, epilepsy, and autism spectrum disorder
ASD or autistic features, DD, ID, epilepsy/seizure
