The MED26 gene encodes a subunit of the CRSP (cofactor required for SP1 activation) Mediator complex, a regulatory complex involved in transcriptional activation and elongation. This complex, along with TFIID, is required for the efficient activation of transcription by the enhancer-binding factor SP1. By working within this complex, it is believed that the MED26 protein plays a role in the phosphorylation of the RNA polymerase II terminal domain, as well as in the recruitment of RNA polymerase II and the Super Elongation Complex (SEC) components AFF4 and CDK9 to the promoter regions of target genes. It is suggested that MED26 functions as a molecular switch, initially interacting with TFIID during transcriptional activation and then exchanging TFIID for polymerase II elongation factors to promote elongation. Through its actions MED26 is found to activate the expression of the MYC, HSP70 and SNAI2 genes.
The MED26 gene is located on the short arm of chromosome 19. It spans a length of 54 kb of DNA and its coding sequence is contained within 3 exons. The gene encodes a 65.4 kDa protein product composed of 600 amino acids. An additional 10 kDa isoform of the MED26 protein exists due to an alternatively spliced transcript variant. The gene is found to be overexpressed in the heart, pancreatic juice and testis.
Monies et al. (2017) outlined the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 5-year-old female, presented with fine motor delay, speech delay, intellectual disability and stereotypic behaviors. Whole exome sequencing helped identify a heterozygous mutation (c.1771T>G, p.L591V) in exon 3 of the patient’s MED26 gene. This gene mutation was considered a candidate for pathogenicity due to several reasons: it was a novel variant predicted to be deleterious, the MED26 gene had an established role in regulating neuronal gene expression, and it had a pLI score of 0.95, indicating that it is likely to be intolerant of loss-of-function mutations. The authors noted that further studies are required to confirm this association.
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