The same homozygous missense variant in the EIF3F gene (c.694T>G;p.Phe232Val) was identified in two recently described individuals who were diagnosed with ASD and presented with additional neurodevelopmental comorbidities (Bar et al., 2024; Lob et al., 2024). The homozygous p.Phe232Val missense variant in EIF3F has previously been associated with an autosomal recessive neurodevelopmental disorder characterized by global developmental delay, intellectual disability, behavioral problems, and hearing loss (Martin et al., 2018; Huffmeier et al., 2021); autism or autistic behavior was reported in a subset of individuals. Martin et al., 2018 had additionally demonstrated in CRISPR-Cas9-edited iPSCs that cells homozygous for the p.Phe232Val variant displayed approximately 27% lower EIF3F protein levels and reduced proliferation rates relative to heterozygous and wild-type cells. De novo missense variants in the EIF3F gene have also been identified in ASD probands from the Autism Sequencing Consortium and the SPARK cohort (Satterstrom et al., 2020; Trost et al., 2022).
Molecular Function
Enables deubiquitinase activity and identical protein binding activity. Contributes to translation initiation factor activity. Involved in IRES-dependent viral translational initiation; protein deubiquitination; and translational initiation. Located in membrane. Part of eukaryotic translation initiation factor 3 complex.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Genetic Diagnostic Yield in Autism Spectrum Disorder (ASD) and Epilepsy Phenotypes in Children with Genetically Defined ASD
