De novo missense variants in the POLR2A gene have been identified in ASD probands from the Autism Sequencing Consortium (Neale et al., 2012; Satterstrom et al., 2020) and the MSSNG cohort (Yuen et al., 2017). Heterozygous variants in the POLR2A gene are responsible for neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (NEDHIB; OMIM 618603), a neurodevelopmental disorder characterized by characterized by early-onset hypotonia, delayed walking, poor speech, and impaired intellectual development; autistic behavior or autism spectrum disorder was reported in a subset of affected individuals (Haijes et al., 2019; Hansen et al., 2021). More recently, Evans et al., 2022 described a 31-year-old female with complex autism spectrum disorder involving epilepsy, strabismus, and self-injurious behavior who was identified with a novel de novo and potentially damaging missense variant in the POLR2A gene.
Molecular Function
This gene encodes the largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a carboxy terminal domain composed of heptapeptide repeats that are essential for polymerase activity. These repeats contain serine and threonine residues that are phosphorylated in actively transcribing RNA polymerase. In addition, this subunit, in combination with several other polymerase subunits, forms the DNA binding domain of the polymerase, a groove in which the DNA template is transcribed into RNA.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Patterns and rates of exonic de novo mutations in autism spectrum disorders.
