Protein truncation is a post-translational modification that can have a major impact on the diversity of the human proteome and the functional repertoire of proteins. It occurs when a change in the DNA sequence of a gene results in the creation of an early stop codon, which terminates translation and produces a shortened or truncated protein. This type of variant can have serious consequences, such as truncated variants in the SCN1A gene leading to Dravet syndrome, a rare form of epilepsy that can cause developmental disability. Truncated proteins are typically subject to nonsense mediated decay (NMD), a cellular mechanism that detects nonsense mutations and prevents expression of truncated proteins, resulting in the loss of function of that copy of the protein.
However, alternative models adapted for protein truncation variants have been proposed, such as a Bayesian modeling framework for the analysis of protein truncation variants and quantitative traits. In some cases, truncated proteins can be functional. For example, expression of truncated proteins such as P3N-ALT by transcriptional slippage (TS) has been reported in negative-stranded RNA viruses, including Ebola and Sendai viruses, members of the Paramyxoviridae family, and a positive-stranded RNA virus, hepatitis C virus (HCV), a member of the Flaviviridae family. This structural characteristic and expression pattern suggested that truncated but functional products produced through TS have not been identified in various species of RNA viruses, and that the coding capacity of the viruses may have been underestimated.
Indels that introduce a premature stop codon to produce a truncated protein are generally considered harmful and useless mutations and have not been subject to further functional analysis. However, comparison of association P values and Bayes Factors for APOC3 truncation variants and plasma triglyceride levels in the Got2d exome sequencing study suggest that some truncated proteins may be functional. In conclusion, protein truncation can have serious consequences for gene function, but it is possible for some truncated proteins to be functional. Further research is needed to better understand how these proteins are expressed and how they affect gene function.