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- Title
Prediction of Functional Consequences of Missense Mutations in ANO4 Gene.
- Authors
Reichhart, Nadine; Milenkovic, Vladimir M.; Wetzel, Christian H.; Strauß, Olaf; Galeazzi, Roberta
- Abstract
The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca2+-dependent ion channels and/or Ca2+-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.
- Subjects
GENETIC mutation; MISSENSE mutation; MOLECULAR dynamics; PROTEIN stability; PROTEIN structure; MUTANT proteins; MEMBRANE proteins
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 5, p2732
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22052732