De novo missense variants in the CERT1 gene have been identified in multiple ASD probands (De Rubeis et al., 2014; Iossifov et al., 2014; Takata et al., 2018; Zhou et al., 2022). Three male patients with impaired intellectual development from the Deciphering Developmental Disorders 2015 study were identified with the same de novo p.Ser132Leu missense variant in the CERT1 gene; one of these three patients also presented with stereotypic behavior. Gehin et al., 2023 characterized 31 unrelated individuals with 22 CERT1 missense variants presenting with a neurodevelopmental syndrome characterized by infantile hypotonia, mild dysmorphic features, variable degrees of intellectual disability, motor and speech delays, increased pain tolerance, and seizures; 19/27 (70%) of the individuals in this study were either diagnosed with autism spectrum disorder (ASD) or presented with possible ASD, and several of the CERT1 missense variants identified in affected individuals were experimentally shown to result in gain-of-function effects.
Molecular Function
This gene encodes a kinase that specifically phosphorylates the N-terminal region of the non-collagenous domain of the alpha 3 chain of type IV collagen, known as the Goodpasture antigen. Goodpasture disease is the result of an autoimmune response directed at this antigen. One isoform of this protein is also involved in ceramide intracellular transport.
