Musante et al., 2026 collected clinical and molecular information from 24 unrelated individuals with mostly heterozygous missense variants in the SF3B3 gene exhibiting a congruent phenotype including autism spectrum disorder, developmental delay, intellectual disability, language and motor delay, multiple congenital anomalies, and distinctive craniofacial features confirmed by GestaltMatcher analysis; three of the individuals included in this report were ASD probands from the Simons Simplex Collection and the SPARK cohort previously reported in Satterstrom et al., 2020, Zhou et al., 2022, and Trost et al., 2022. Additional functional assessment of fibroblasts from a subset of individuals with SF3B3 missense variants in Musante et al., 2026 identified reduced SF3B3 protein levels, differential gene expression, increased alternative splicing events, and cell-cycle abnormalities compared to controls.
Molecular Function
This gene encodes subunit 3 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. Subunit 3 has also been identified as a component of the STAGA (SPT3-TAF(II)31-GCN5L acetylase) transcription coactivator-HAT (histone acetyltransferase) complex, and the TFTC (TATA-binding-protein-free TAF(II)-containing complex). These complexes may function in chromatin modification, transcription, splicing, and DNA repair.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
A novel spliceosomopathy caused by de novo SF3B3 variants
