Frameshift mutation
A frameshift mutation is an insertion or deletion that changes how a coding sequence is grouped into codons, often altering every downstream amino acid.
What a frameshift mutation is
A frameshift mutation is a genetic change that disrupts the grouping of a coding sequence into three-base codons. It usually happens when one or more bases are inserted or deleted, but the number changed is not a multiple of three. Because the ribosome reads codons in fixed triplets, the downstream message can be reinterpreted.
Why multiples of three matter
Adding or removing three bases may add or remove one codon while leaving the downstream reading frame intact. Adding or removing one, two, four, or five bases shifts the triplet grouping. That shift can change many amino acids after the mutation, even if the DNA change itself is small.
Downstream consequences
After a frameshift, the new codons often specify a different amino acid sequence. The shifted frame may soon encounter a stop codon, producing a shortened protein. If the altered mRNA is recognized as faulty, the cell may also degrade it through surveillance pathways such as nonsense-mediated decay.
Insertions and deletions
Frameshifts are commonly caused by indels, meaning insertions or deletions. They can arise during DNA replication, through errors in repair, or in regions with repeated bases where the copying machinery can slip. Not every indel causes a frameshift; the key is whether the coding frame changes.
Relation to ORFs
An open reading frame depends on a consistent reading frame from start to stop. A frameshift inside an ORF can create a new downstream amino acid sequence and a new stop position. In genome annotation and variant interpretation, this is why frameshift variants are often treated as strong candidates for disrupting protein function.
Not always identical in impact
Frameshift effects depend on where the mutation occurs, which transcript is affected, whether the altered region is translated, and whether the protein can tolerate changes near one end. A frameshift near the beginning of an essential coding region is often more damaging than one near the very end, but context matters.
How variants are described
Clinical and research descriptions often mark frameshift protein changes with the abbreviation fs. A notation may indicate where the new reading frame begins and where a new stop codon appears. These descriptions are shorthand for a molecular effect, not a diagnosis by themselves.
Why it matters
Frameshift mutations show how tightly protein coding depends on triplet reading. A one-base change can rewrite an entire downstream protein segment. That makes frameshifts important in genetics, disease interpretation, cancer genomics, genome editing, and the basic logic of how DNA becomes protein.