Two de novo variants (one nonsense, one missense) in the INTS6 gene were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Krumm et al., 2015 reported that no de novo SNVs in this gene were observed in SSC unaffected siblings (de novo SNV P-value <0.05), and no rare effect types were reported in the Exome Variant Server. This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015). Peng et al., 2025 reported a cohort of 23 families harboring monoalleleic likely gene-disruptive or de novo missense variants in the INTS6 gene presenting with a neurodevelopmental disorder characterized by speech-language problems (90.9%), autism spectrum disorder (77.3%), motor delay (72.2%), intellectual disability (72.2%), and sleep disturbance (62.5%); in the same report, behavioral assessment of a nervous-system conditional knockout mouse model demonstrated that Ints6 cKO heterozygous mice displayed deficits in social novelty preference, spatial memory, and hyperactivity, mirroring phenotypes observed in individuals with INTS6 variants.
Molecular Function
The protein encoded by this gene is a DEAD box protein that is part of a complex that interacts with the C-terminus of RNA polymerase II and is involved in 3' end processing of snRNAs.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder
