Why can a mutation create a shortened and nonfunctional protein?

A mutation can result in a shortened and nonfunctional protein primarily through two mechanisms:

• Nonsense Mutations: These occur when a base substitution creates a stop codon in a position where one did not previously exist. This causes the premature termination of protein synthesis, leading to a truncated protein that typically lacks its intended biological function.12
• Frameshift Mutations: These are caused by the insertion or deletion of DNA bases that are not in multiples of three. Because the genetic code is read in triplets, this shifts the reading frame of the gene. All downstream codons are altered, often resulting in a protein sequence that contains a "tail" of meaningless amino acids or leads to premature termination, rendering the final product nonfunctional.12

In both cases, the disruption of the normal amino acid sequence prevents the protein from folding or interacting correctly, which is essential for its biological activity.12