Editing Missense mutation (section)

== Impact on Protein Function ==
Missense mutation refers to a change in one amino acid in a [[protein]] arising from a [[point mutation]] in a single nucleotide.<ref name=":11" /> Amino acids are the building blocks of proteins. Missense mutations are a type of [[nonsynonymous substitution]] in a DNA sequence.<ref name=":15">{{Cite book |last=Brown |first=TA |url=https://www.ncbi.nlm.nih.gov/books/NBK21114/ |title=Genomes. 2nd edition. |date=2002 |publisher=Oxford: Wiley-Liss |chapter=Chapter 14, Mutation, Repair and Recombination}}</ref> Two other types of nonsynonymous substitutions are [[nonsense mutation]]s, in which a codon is changed to a premature [[stop codon]] that results in the resulting protein being cut short,<ref>{{Cite journal |last1=Chu |first1=Duan |last2=Wei |first2=Lai |date=2019-04-16 |title=Nonsynonymous, synonymous and nonsense mutations in human cancer-related genes undergo stronger purifying selections than expectation |journal=BMC Cancer |volume=19 |issue=1 |pages=359 |doi=10.1186/s12885-019-5572-x |doi-access=free |issn=1471-2407 |pmc=6469204 |pmid=30991970}}</ref> and [[Stop codon#Nonstop|nonstop mutation]]s, in which a stop codon deletion results in a longer but nonfunctional protein.<ref>{{Cite journal |last1=Pal |first1=Jagriti |last2=Riester |first2=Marisa |last3=Ganner |first3=Athina |last4=Ghosh |first4=Avantika |last5=Dhamija |first5=Sonam |last6=Mookherjee |first6=Debdatto |last7=Voss |first7=Christian |last8=Frew |first8=Ian J. |last9=Kotsis |first9=Fruzsina |last10=Neumann-Haefelin |first10=Elke |last11=Spang |first11=Anne |last12=Diederichs |first12=Sven |date=2025-02-14 |title=Nonstop mutations cause loss of renal tumor suppressor proteins VHL and BAP1 and affect multiple stages of protein translation |journal=Science Advances |language=en |volume=11 |issue=7 |doi=10.1126/sciadv.adr6375 |issn=2375-2548 |pmc=11817944 |pmid=39937911|bibcode=2025SciA...11R6375P }}</ref> The latter two types are not considered to be missense mutations. 
[[File:Point mutations-en.png|thumb|350x350px|Point mutation categories. Missense mutations are a type of nonsynonymous point mutation. ]]
Missense mutations can render the resulting protein nonfunctional,<ref name=":6">{{cite journal | vauthors = Minde DP, Anvarian Z, Rüdiger SG, Maurice MM | title = Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer? | journal = Molecular Cancer | volume = 10 | issue = 1 | pages = 101 | date = August 2011 | pmid = 21859464 | pmc = 3170638 | doi = 10.1186/1476-4598-10-101 | doi-access = free }}</ref> due to misfolding of the protein.<ref name=":0">{{cite journal | vauthors = Stefl S, Nishi H, Petukh M, Panchenko AR, Alexov E | title = Molecular mechanisms of disease-causing missense mutations | journal = Journal of Molecular Biology | volume = 425 | issue = 21 | pages = 3919–3936 | date = November 2013 | pmid = 23871686 | pmc = 3796015 | doi = 10.1016/j.jmb.2013.07.014 }}</ref> These mutations are responsible for human diseases, such as [[Epidermolysis bullosa]],<ref>{{cite journal | vauthors = Miura Y, Nakagomi S | title = Management of Cutaneous Manifestations of Genetic Epidermolysis Bullosa: A Multiple Case Series | journal = Journal of Wound, Ostomy, and Continence Nursing | volume = 48 | issue = 5 | pages = 453–459 | date = September 2021 | pmid = 34495939 | doi = 10.1097/WON.0000000000000784 }}</ref> [[sickle-cell disease]],<ref>{{cite journal | vauthors = Piel FB, Steinberg MH, Rees DC | title = Sickle Cell Disease | journal = The New England Journal of Medicine | volume = 376 | issue = 16 | pages = 1561–1573 | date = April 2017 | pmid = 28423290 | doi = 10.1056/NEJMra1510865 | veditors = Longo DL }}</ref> [[Superoxide dismutase|SOD1]] mediated [[Amyotrophic lateral sclerosis|ALS]], and a substantial number of [[cancer]]s.<ref>{{cite journal | vauthors = Boillée S, Vande Velde C, Cleveland DW | title = ALS: a disease of motor neurons and their nonneuronal neighbors | journal = Neuron | volume = 52 | issue = 1 | pages = 39–59 | date = October 2006 | pmid = 17015226 | doi = 10.1016/j.neuron.2006.09.018 | doi-access = free }}</ref><ref>{{cite news | vauthors = Henderson M |title=A Monumental Breakthrough? |url=https://www.newspapers.com/image/660719439/ |access-date=21 November 2022 |work=The News-Star |date=May 1, 2020 |pages=A1, A7 |language=en}}</ref>

Not all missense mutations lead to appreciable protein changes.<ref name=":15" /><ref name=":16" /> An amino acid may be replaced by a different amino acid of very similar chemical properties in which case the protein may still function normally; this is termed a [[Silent mutation|conservative mutation]].<ref name=":16">{{Cite journal |last1=Kimchi-Sarfaty |first1=Chava |last2=Oh |first2=Jung Mi |last3=Kim |first3=In-Wha |last4=Sauna |first4=Zuben E. |last5=Calcagno |first5=Anna Maria |last6=Ambudkar |first6=Suresh V. |last7=Gottesman |first7=Michael M. |date=2007-01-26 |title=A "Silent" Polymorphism in the MDR 1 Gene Changes Substrate Specificity |url=https://www.science.org/doi/10.1126/science.1135308 |journal=Science |language=en |volume=315 |issue=5811 |pages=525–528 |doi=10.1126/science.1135308 |pmid=17185560 |bibcode=2007Sci...315..525K |issn=0036-8075}}</ref> Alternatively, the amino acid substitution could occur in a region of the protein which does not significantly affect the protein secondary structure or function.<ref name=":15" /> Lastly, when more than one codon codes for the same amino acid (termed "degenerate coding"), the resulting mutation does not produce any change in translation and hence no change in protein is observed; degenerate coding would be classified as a [[synonymous substitution]],<ref>{{Cite journal |last=Wang |first=Shouyu |last2=Li |first2=Lijuan |last3=Tao |first3=Ruiyang |last4=Gao |first4=Yuzhen |date=2017-06-01 |title=Ion channelopathies associated genetic variants as the culprit for sudden unexplained death |url=https://linkinghub.elsevier.com/retrieve/pii/S037907381730107X |journal=Forensic Science International |volume=275 |pages=128–137 |doi=10.1016/j.forsciint.2017.03.006 |issn=0379-0738|url-access=subscription }}</ref> or a silent mutation, and not a missense mutation.<ref name=":15" />