Relevance to Autism

Bou-Rouphael et al., 2025 described a cohort of 15 unrelated individuals with de novo likely deleterious variants in the SF1 gene presenting with neurodevelopmental disorders of variable severity; all individuals presented with developmental delay during the first years of life and mild facial features, and autism spectrum disorder was the most common neurodevelopmental disorder among individuals aged 3 years of older (n=9). Additional functional studies in neuronal progenitor cells in this report demonstrated that SF1 downregulation altered gene expression and alternative splicing programs, particularly in genes involved in neuronal differentiation, synaptic transmission, and axonal guidance. Ultra-rare de novo non-coding variants in the SF1 gene have been previously reported in ASD probands from the Simons Simplex Collection (Iossifov et al, 2014).

Molecular Function

This gene encodes a nuclear pre-mRNA splicing factor. The encoded protein specifically recognizes the intron branch point sequence at the 3' splice site, together with the large subunit of U2 auxiliary factor (U2AF), and is required for the early stages of spliceosome assembly. It also plays a role in nuclear pre-mRNA retention and transcriptional repression. The encoded protein contains an N-terminal U2AF ligand motif, a central hnRNP K homology motif and quaking 2 region which bind a key branch-site adenosine within the branch point sequence, a zinc knuckles domain, and a C-terminal proline-rich domain.

External Links

References