Arginine CGA codon nonsense mutation (Arg-CGA PTC)

The Arginine CGA codon nonsense mutation is a specific genetic alteration where a cytosine-to-thymine transition at a CpG dinucleotide converts the Arginine-encoding CGA codon into a TGA premature termination codon (PTC). This specific mutation is one of the most common causes of genetic disease due to the inherent instability of methylated cytosines at CpG sites, which are prone to spontaneous deamination (Mort et al., 2008; PMID: 18451181). The resulting PTC leads to the synthesis of truncated, typically non-functional proteins and often triggers nonsense-mediated mRNA decay (NMD), significantly reducing the abundance of the transcript (Keeling et al., 2014; PMID: 25043337). In the context of pharmacology, this mutation is the primary target for nonsense suppression or read-through therapies. These therapeutic agents, such as Ataluren or certain aminoglycosides, interact with the ribosome to decrease the stringency of codon-anticodon pairing at the PTC (Welch et al., 2007; PMID: 17443182). This allows for the insertion of a near-cognate amino acid, enabling the translation machinery to continue to the natural stop codon and restore the production of a full-length, functional protein (Linde and Kerem, 2008; PMID: 18382662).

Other names

CGA to TGA mutationArginine-to-Stop mutationArg nonsense mutationPremature termination codon at CGACGA nonsense mutation

Nonsense suppression (read-through) induction