A frameshift mutation (also called a frameshift or a framing error) is a genetic mutation caused by indels, ie. inserts or deletes a number of nucleotides that is not evenly divisible by three from a DNA sequence. Due to the triplet nature of gene expression by codons, the insertion or deletion can disrupt the reading frame, or the grouping of the codons, resulting in a completely different translation from the original. The earlier in the sequence the deletion or insertion occurs, the more altered the protein produced is.

A frameshift mutation causes the reading of codons to be different, so all codons after the mutation (with a few exceptions due to redundancy) will code for different amino acids. Furthermore, the stop codon “UAA, UGA, or UAG” will not be read, or a stop codon could be created at an earlier site. The protein being created could be abnormally short, abnormally long, and/or contain the wrong amino acids. It will most likely not be functional.

Frameshift mutations frequently result in severe genetic diseases. A frameshift mutation is responsible for the disabling of the CCR5 HIV receptor and some types of familial hypercholesterolemia (Lewis, 2005, p. 227-228). Frameshift mutations can also be beneficial.

Frameshifting may also occur during protein translation, producing different proteins from overlapping open reading frames, such as the gag-pol-env retroviral proteins. This is fairly common in viruses and also occurs in bacteria and yeast (Farabaugh, 1996).