frameshift mutation
A genetic alteration that shifts the reading frame of protein translation, typically resulting in a truncated, nonfunctional protein product.
Full Definition
A frameshift mutation occurs when insertions or deletions (indels) of nucleotides change the reading frame during protein translation, altering all downstream amino acids. These mutations typically result in premature stop codons and truncated proteins that lose their normal function. In oncology, frameshift mutations often act as loss-of-function alterations in tumor suppressor genes and are frequently targetable through specific therapeutic approaches like nonsense-mediated decay inhibitors or immunotherapy. The clinical significance depends on the affected gene and the location of the mutation within the coding sequence. Editors should recognize that frameshift mutations are generally considered pathogenic when they occur in critical tumor suppressor genes.
Usage
Usage note: Hyphenate as compound modifier; distinguish from missense mutations which change single amino acids.
In Context
- "A frameshift mutation in exon 4 of BRCA1 resulted in loss of protein function." — Genetic test report
- "The two-nucleotide deletion caused a frameshift mutation leading to early termination." — Variant classification report