Novel enhancer mediates the readthrough loci and gene expressions associated with fabry disease.

Fabry disease (FD) is a rare genetic condition caused by mutations in the gene, located on the X chromosome in the readthrough genomic region. This gene produces an enzyme called alpha-galactosidase A (α-Gal A). When the enzyme does not function properly due to the mutations, it causes harmful substances called globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) to build up in the body's lysosomes. This accumulation can damage the kidneys, heart, eyes, and nervous system. Recent studies have shown that the readthrough loci, which include and genes, as well as the regulatory sequence known as the bidirectional promoter, may also play a role in FD. However, the involvement of enhancer RNAs (eRNAs) in FD is still poorly understood despite their known role in various diseases. To investigate this further, we studied an enhancer called GH0XJ101390 and showed its genomic setting in the readthrough region; the eRNA is rich in Homotypic Clusters of TFBSs (HCTs) type and hosts a CpG Island (CGI). To test the functional correlation further with , , and , we used siRNAs to knock down GH0XJ101390 in human kidney embryonic cells 293T. The results showed a significant decrease in and expression and a non-significant decrease in expression. These findings could have important implications for understanding the regulatory mechanisms of GH0XJ101390 and its potential role in FD. A better understanding of these mechanisms may improve diagnostic and therapeutic methods for FD, which could ultimately benefit patients with this rare condition.