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Missense Mutation

What Is It, Causes, and More

Author: Anna Hernández, MD

Editors: Alyssa Haag, Józia McGowan, DO

Illustrator: Jillian Dunbar

Copyeditor: David G. Walker


What is a missense mutation?

A missense mutation is an alteration in the DNA that results in a different amino acid being incorporated into the structure of a protein. At a molecular level, DNA is made up of two strands of four nucleotides called alanine, cytosine, guanine, and thiamine (i.e., A, C, G, T, respectively). In order to produce a protein, DNA must first be transformed into messenger RNA, or mRNA, by an enzyme called RNA polymerase. This mRNA is then encoded so that any three nucleotides correspond to a specific codon, which codes for a specific amino acid, or is a stop codon, which indicates that protein synthesis is complete. In the final step of translation, specialized proteins called ribosomes use the mRNA molecule to read each codon and match them with the corresponding amino acids that will ultimately make up the final protein.

Missense mutations occur when a single nucleotide base in a DNA sequence is swapped for another one, resulting in a different codon and, therefore, a different amino acid. These mutations are quite common and, in most cases, they don’t affect the overall shape and function of the protein. However, when the amino acid substitution involves two amino acids with very different chemical properties, missense mutations can lead to significant changes in protein function. In such cases, they are known as non-conservative missense mutations.

What is the difference between a nonsense mutation and a missense mutation?

Nonsense mutations replace an amino acid codon with an early stop codon, which prematurely signals the ribosome to stop building a protein. Unlike missense mutations, nonsense mutations almost always have serious consequences. 

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What causes a missense mutation?

Missense mutations can happen spontaneously or be induced by various kinds of mutagens. Mutagens include physical agents, like UV rays and chemical molecules, as well as biological agents, like certain viruses. 

What conditions are caused by a missense mutation?

The most common condition associated with a missense mutation is sickle cell disease, also known as drepanocytosis. With sickle cell disease, the hemoglobin protein has a mutation that changes the amino acid glutamate, which is hydrophilic (i.e., attracted to water), for valine, which is hydrophobic (i.e., repels water). The resulting hemoglobin is more frail and can be destroyed more easily, which makes it harder for red blood cells to carry as much oxygen in the blood. 

What are the most important facts to know about a missense mutation?

A missense mutation is an alteration in the DNA sequence that results in a different amino acid being incorporated into the structure of a protein. Depending on which amino acid it codes for, missense mutations can be conservative (i.e., the resulting protein is functional) or nonconservative (i.e., the resulting protein is non-functional). 

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Related links

DNA structure
Transcription of DNA
DNA damage and repair
DNA mutations
Mendelian genetics and punnett squares

Resources for research and reference

Al Aboud, N.M., Basit, H., & Al-Jindan, F.A. (2021). Genetics, DNA damage and repair. In: StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK541088/

Clark, D. P., Pazdernik, N. J., & McGehee, M. R. (2018). Molecular Biology (3rd ed.). Academic Cell.

Stefl, S., Nishi, H., Petukh, M., Panchenko, A. R., & Alexov, E. (2013). Molecular mechanisms of disease-causing missense mutations. Journal of molecular biology, 425(21), 3919–3936. DOI: 10.1016/j.jmb.2013.07.014