Trio-based whole-exome sequencing of 168 patients with low-functioning ASD at Sun Yat-sen Memorial Hospital in Wu et al., 2025 identified a de novo loss-of-function variant in the TCF12 gene in a patient clinically diagnosed with ASD based on DSM-5 criteria and presenting with global developmental delay/intellectual disability. Additional de novo loss-of-function variants, as well as a de novo missense variant prediced to be deleterious by CADD, REVEL, and MPC, were previously reported in TCF12 in ASD probands from the MSSNG cohort, the SPARK cohort, and the Autism Sequencing Consortium (Yuen et al., 2016; Zhou et al., 2022; Fu et al., 2022; Trost et al., 2022). TCF12 was identified in Wang et al., 2020 as an novel NDD risk gene, with ultra-rare likely gene-disruptive variants reaching FDR significance following a combined analysis of new ASD and NDD cases with published data. Autism spectrum disorder was been reported in a subset of individuals with craniosynostosis 3 (Sharma et al., 2013; Paumard-Hernndez et al., 2015).
Molecular Function
The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Heterozygous mutations in this gene are responsible for craniosynostosis 3 (OMIM 615314).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Predicting the diagnostic efficacy of trio-based whole exome sequencing in children with low-function autism spectrum disorders: a multicenter study
