Relevance to Autism

TAF4 was identified as an ASD candidate gene based on having a p-value < 0.001 following DeNovoWEST analysis of de novo variants in 16,877 ASD trios from the Simons Simplex Collection, the Autism Sequencing Consortium, the MSSNG cohort, and the SPARK cohort in Zhou et al., 2022; among the de novo variants observed in ASD cases in this analysis were three de novo loss-of-function variants. An additional de novo missense variant in TAF4 was identified in an ASD proband from the Simons Simplex Collection (Werling et al., 2018). Janssen et al., 2022 presented a cohort of eight individuals with de novo putative loss-of-function variants in TAF4 and expressing phenotypes consistent with a neurodevelopmental syndrome, including speech delay, intellectual disability, behavioral abnormalities, and facial dysmorphisms; autism spectrum disorder was reported in one of these individuals, while autistic features were reported in two others.

Molecular Function

Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the larger subunits of TFIID that has been shown to potentiate transcriptional activation by retinoic acid, thyroid hormone and vitamin D3 receptors. In addition, this subunit interacts with the transcription factor CREB, which has a gluta

External Links

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