A de novo missense variant that was predicted to be damaging was identifed in the SUPT16H gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. Bina et al., 2020 identified five individuals with de novo variants affecting the SUPT16H gene, all of whom presenting with gross motor delay, delayed or absent speech, and cognitive delay/intellectual disability; two of the five individuals from this study also presented with autistic features. Microdeletions and microduplications involving the CHD8 and SUPT16H genes have also been observed in patients presenting with a spectrum of neurodevelopmental phenotypes, including ASD/autistic features (Drabova et al., 2015; Smyk et al., 2016; Yasin et al., 2019; Smol et al., 2020). Lee et al., 2026 expanded the genotypic and phenotypic spectrum by identifying 24 additional individuals from 22 unrelated families harboring ultrarare heterozygous missense or truncating SUPT16H variants and sharing overlapping clinical features including intellectual disability, autism spectrum disorder, hypotonia, and chracteristic craniofacial dysmorphism; furthermore, a supt16h knockout zebrafish model recapitulated key patient phenotypes including developmental delay, craniofacial anomalies, and hypotonia, and disease-associated SUPT16H variants demonstrated differential rescue of developmental defects in supt16h-deficient embryos, indicating variant-specific loss-of-function effects in vivo.
Molecular Function
The SUPT16H gene encodes for a component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder
