Fig. 3: Schematic showing how UTR variants can cause disease through disrupting RNA splicing.
From: The role of untranslated region variants in Mendelian disease: a review
A 5′UTR variants in PAX6 are a common cause of aniridia. These variants are thought to cause skipping of exon three, which contains the stop codon of an upstream open reading frame (uORF), converting it into an upstream overlapping ORF (uoORF) and resulting in lower translation of the PAX6 coding sequence (CDS). B Variants that disrupt the acceptor splice site of the final exon in the 5′UTR remove the start codon of the CDS. C 3′UTR variants that create cryptic donor splice sites further than 55 bps downstream of the end of the CDS are predicted to lead to transcript degradation through nonsense-mediated decay (NMD).
