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Difference between Missense and Nonsense Mutation

Genetic mutations are permanent alterations to the nucleotide sequence of a gene. Mostly, these mutations are advantageous in enabling evolution and generating new desirable traits. Some could be problematic mutations and result in abnormalities.

Depending on where it occurs and where it can change the function of essential proteins, the gene variants can affect health differently. Mutations can be classified based on the effect on the DNA sequence or the encoded protein. The types of variants are as follows:

  • Insertion
  • Deletion
  • Substitution
  • Deletion-insertion
  • Inversion
  • Duplication
  • Repeat expansion
  • Frameshift

Substitution – This variant type substitutes or replaces a nucleotide with another. Furthermore, based on the effect it has on the production of proteins from the changed gene, substitution variants can be classified as:

  • Missense
  • Nonsense

The nonsense and missense mutations vary in the fact that the missense mutation inserts a different codon other than the stop codon to the gene sequence, resulting in the non-synonymous amino acid in the polypeptide chain. On the other hand, the nonsense mutation inserts a stop codon into the gene sequence, resulting in premature chain termination.

Missense Mutation

  • This substitution variant type is when the change in nucleotide leads to the replacement of one amino acid or protein building block with another in the protein composed of the gene.
  • Modification in amino acids could be essential in the functioning of a protein.
  • Some of these mutations cause amino acids to be incorporated, causing the protein to be more effective.

Nonsense Mutation

  • This substitution variant type is where rather than inducing a change in the amino acid, the modified DNA sequence causes a stop signal which signals the cell to prematurely stop building a protein – the premature termination of translation.
  • It leads to a shortened protein that does not function properly or disintegrated or non-functional.
  • In other words, this point mutation introduces a premature stop codon in the mRNA sequence; wherein a single nucleotide alteration results in the introduction of a stop codon. When this occurs, it terminates the translation without finishing the complete translation, resulting in the protein becoming shortened abnormally.

Key Difference between Missense and Nonsense Mutation

The table below depicts the difference between Missense and Nonsense Mutation:

Missense Mutation
Nonsense Mutation
What is it?
Single base-pair substitutions alter the genetic code, thus producing amino acids different from the normal amino acids at that location. This alteration causes a sense codon corresponding to one of the 20 amino acids given by the genetic code to be altered to a chain-termination codon.
Type of codon introduced
Distinct codon Stop codon at the mutation site.
Is a different amino acid substituted?
Yes No
Are proteins produced functional?
It could be non-functional, functional or can have a different function from the actual protein. Usually non-functional.
What is the outcome?
Distinct amino acids – non conservative or conservative.

Results in different amino acid sequence.

At the mutation site, it leads to premature chain termination.

Results in a shorter and incomplete protein product.

Resultant protein
Non-conserved or conserved protein. Truncated protein
Resultant abnormalities
Epidermolysis bullosa, sickle cell disease Beta thalassemia, cystic fibrosis

You read some differences between Missense and Nonsense Mutation. For more such articles, visit us at BYJU’S NEET.

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