A de novo loss-of-function (LoF) variant in the MED13 gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second de novo LoF variant in this gene was identified by whole genome sequencing in an ASD proband from a simplex family as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of two de novo LoF variants in ASD cases, a probability of LoF intolerance rate (pLI) > 0.9, and a higher-than expected mutation rate (a false discovery rate < 15%), MED13 was determined to be an ASD candidate gene in Yuen et al., 2017. Genetic and phenotypic characterization of a cohort of 13 individuals affected with intellectual disability or developmental delay and harboring protein-altering variants in the MED13 gene in Snijders Blok et al., 2018 demonstrated that five of these cases also had autism spectrum disorder (ASD), while three cases were also diagnosed with ADHD. Additional de novo loss-of-function variants in the MED13 gene were reported in ASD probands from the Autism Sequencing Consortium, the MSSNG cohort, and the SPARK cohort in Zhou et al., 2022; a two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in this report identified MED13 as a gene reaching exome-wide significance (P < 2.5E-06).
Molecular Function
The MED13 gene encodes a component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder
