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Characterization of human frataxin missense variants in cancer tissues

Research output: Contribution to journalArticle

Maria Petrosino, Alessandra Pasquo, Leonore Novak, Angelo Toto, Stefano Gianni, Elide Mantuano, Liana Veneziano, Velia Minicozzi, Annalisa Pastore, Rita Puglisi, Emidio Capriotti, Roberta Chiaraluce, Valerio Consalvi

Original languageEnglish
Pages (from-to)1400-1413
Number of pages14
JournalHuman Mutation
Issue number9
Early online date10 May 2019
Accepted/In press10 May 2019
E-pub ahead of print10 May 2019
Published1 Sep 2019


King's Authors


Human frataxin is an iron binding protein involved in the mitochondrial Fe‐S clusters assembly, a process fundamental for the functional activity of mitochondrial proteins. Decreased level of frataxin expression is associated with the neurodegenerative disease Friedreich ataxia. Defective function of frataxin may cause defects in mitochondria, leading to increased tumorigenesis. Tumour initiating cells show higher iron uptake, a decrease in iron storage and a reduced Fe‐S clusters synthesis and utilization. In this study we selected, from COSMIC database, the somatic human frataxin missense variants found in cancer tissues p.D104G, p.A107V, p.F109L, p.Y123S, p.S161I, p.W173C, p.S181F, and p.S202F to analyze the effect of the single amino acid substitutions on frataxin structure, function and stability. The spectral properties, the thermodynamic and the kinetic stability, as well as the molecular dynamics of the frataxin missense variants found in cancer tissues point to local changes confined to the environment of the mutated residues. The global fold of the variants is not altered by the amino acid substitutions, however some of the variants show a decreased stability and a decreased functional activity in comparison to that of the wild type protein.

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