Missense Mutation

Missense Mutation Definition

A missense mutation is a type of point mutation in which a different amino acid is placed within the produced protein, other than the original. In the process of converting DNA into protein, the language of DNA must be translated into the language of proteins. During this process, a change in the structure of DNA, or a mutation, can change the sequence of amino acids which creates a protein. If it does not change the structure or function of the protein, it may be considered a silent mutation. If it does change the protein, it is considered a missense mutation.

Point mutationsThe DNA is read in units of three, called codons. These codons call for one of 21 amino acids, which the ribosome complex will assemble in order by reading the messenger RNA, or mRNA. If there are 3 spots in a codon, and 4 possible nucleotides to go in that spot, the codons can call for 64 different signals. Since there are only 21 amino acids, many of these codons call for the same amino acid. If a mutation calls for the same amino acid as before the mutation, it is considered silent.

On the other hand, several other codons also call for signals to stop and process the protein. In this case, instead of adding an amino acid, the sequence is ended and the protein is ejected from the ribosome. In this case, the mutation would be a nonsense mutation, because the protein would be incomplete. A missense mutation continues the chain of the protein, but it may also interfere with the functioning of the protein. To this end, there are two basic types of missense mutation.

Types of Missense Mutation


In a conservative missense mutation, the amino acid replaced is similar in function and shape to the amino acid being replaced. A conservative missense mutation may result in loss of function, but it may only be minor. In the context of population genetics and ecology, a missense mutation may not necessarily be a negative thing. 

A slowed or slightly changed function of a protein may actually increase the fitness of an organism. If the product of the protein needs to be regulated, or is currently hindering the fitness of the organism, a change may be beneficial. A conservative missense mutation is typically changes the function of a protein less drastically than the other type of missense mutation.


In a non-conservative missense mutation, a completely different kind of amino acid is added to the chain. Where a polar amino acid was present, a non-polar amino acid will be added. This type of missense mutation can greatly change the function of a protein, as it will likely change the shape and structure of the protein.

Proteins have various levels of structure, all which depend upon the DNA. If a missense mutation changes an amino acid, it first changes the primary structure, or the basic sequence of amino acids. The secondary structure of proteins consists of patterns and structures formed by interactions between these amino acids. A missense mutation could completely disrupt a form such as an alpha helix or beta sheet. 

These structures can be crucial to the overall tertiary structure of the protein, or its general shape and size. This structure informs how the protein interacts with other molecules within the environment. A non-conservative missense mutation may completely change these interactions. At the final level of protein structure, quaternary structure, a missense mutation can even prevent a protein from joining a larger protein complex it is intended to be a part of. This can render entire biochemical pathways useless, or give them a completely new use.

Missense Mutation Example

A common and well-known example of a missense mutation is sickle-cell anemia, a blood disease. People with sickle-cell anemia have a missense mutation at a single point in the DNA. This missense mutation calls for a different amino acid, and affects the overall shape of the protein produced. 

This, in turn, causes the entire shape of blood cells to be different. People with the disease experience symptoms of not being able acquire oxygen efficiently, and experience blood clotting. However, they are partially protected from blood borne parasites which live in blood cells. Malaria is a disease caused by these parasites, and people with sickle-cell anemia have an inherent defense against the parasite. Their sickle-shaped blood cells cannot support the life cycle of the parasite.

The missense mutation which causes all of this is the difference of one nucleotide. It is first translated into mRNA, then into a protein. The missense mutation causes a valine to be placed where a glutamic acid normally goes. This non-conservative missense mutation causes the shape of the protein, hemoglobin, to change. 

Where normal hemoglobin separates, the mutated hemoglobin forms long chains. These chains, when incorporated into blood cells, change their shape and force them into a sickle. 

Many other anemias and various genetic diseases are caused by a missense mutation. All proteins are reliant on the sequence of amino acids which makes it up. While mutations may sometimes bring benefits to an organism, they more often disrupt a stable and relied-upon process. In disrupting even a single protein, cells can become functionless, or at least struggle to function.


What is a missense mutation?

A missense mutation is a type of genetic mutation that alters a single nucleotide in a DNA sequence, resulting in the substitution of one amino acid for another in the protein encoded by that gene. Missense mutations can have varying effects on protein structure and function, depending on the location and nature of the amino acid substitution.

What are the consequences of missense mutations?

The consequences of missense mutations can vary widely, depending on the location and nature of the amino acid substitution. Some missense mutations have no effect on protein structure or function, while others can disrupt protein folding, stability, or activity, leading to disease or developmental abnormalities. In some cases, missense mutations can also confer a selective advantage, for example by increasing resistance to certain drugs or toxins.

How are missense mutations detected?

Missense mutations can be detected through a variety of molecular techniques, including PCR-based methods, DNA sequencing, and bioinformatics analysis. In some cases, missense mutations may also be detected through biochemical assays that measure changes in protein structure or function.

What are some examples of diseases caused by missense mutations?

Missense mutations are implicated in many genetic diseases, including cystic fibrosis, sickle cell anemia, Huntington’s disease, and various forms of cancer. In some cases, missense mutations may also contribute to complex diseases with multiple genetic and environmental risk factors, such as Alzheimer’s disease or type 2 diabetes.

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