Relevance to Autism

A de novo loss-of-function variant and multiple de novo missense variants in the TRRAP gene have been observed in ASD probands (Iossifov et al., 2014; Yuen et al., 2017), while multiple de novo missense variants in this gene have also been identified in probands with unspecified developmental disorders (Deciphering Developmental Disorders Study 2017) or epilepsy (Epi4K Consortium 2013). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified TRRAP as a gene with an excess of missense variants (false discovery rata < 5%, count >1) (Coe et al., 2018). Cogne et al., 2019 reported 24 individuals with 17 distinct de novo or apparently de novo missense variants that presented with two distinct clinical spectra: the first was a complex multi-systemic syndrome associated with various malformations of the brain, heart, kidneys and genitourinary system and a wide range of intellectual functioning in individuals with variants clustered between animo acids 1031 and 1159; the second spectrum manifested with autism spectrum disorder and/or intellectual disability and epilepsy in individuals with variants outside of this region.

Molecular Function

This gene encodes a large multidomain protein of the phosphoinositide 3-kinase-related kinases (PIKK) family. The encoded protein is a common component of many histone acetyltransferase (HAT) complexes and plays a role in transcription and DNA repair by recruiting HAT complexes to chromatin.

External Links

References