Rare and potentially damaging missense variants in the SRSF1 gene have been previously identified in two ASD probands (Satterstrom et al., 2020; Zhou et al., 2022). Bogaert et al., 2023 identified a cohort of 17 individuals with heterozygous germline SRSF1 variants who presented with a neurodevelopmental syndrome characterized by developmental delay and intellectual disability, hypotonia, and neurobehavioral problems (includiing autistic features and/or stereotypy in a subset of affected individuals) with variable skeletal and cardiac abnormalities; functional assessment in Drosophila demonstrated that all loss-of-function variants and 5 out of 7 missense variants in this gene were pathogenic and resulted in loss of SRSF1 splicing activity, which correlated with a detectable and specific DNA methylation signature in blood-derived DNA from affected individuals.
Molecular Function
This gene encodes a member of the arginine/serine-rich splicing factor protein family. The encoded protein can either activate or repress splicing, depending on its phosphorylation state and its interaction partners.
