Mechanisms conferring protein loss and toxic gain-of-function effects. The diagram illustrates pathogenic mutations (repeat expansions, deletions, point mutations) that may occur either in noncoding or coding regions of the genome (left and right sides, respectively).
Protein loss-of-function. Haploinsufficiency can occur when the level of a particular mRNA is down-regulated due to mutations in noncoding regions of genes such as in promoters/introns, or if the promoter is subjected to histone/DNA modifications (transcriptional repression)
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