In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
| Заглавие |
In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function
|
|
| Автор |
Shinwari, K.
Wu, Y. Rehman, H. M. Xiao, N. Bolkov, M. Tuzankina, I. Chereshnev, V. |
|
| Тематика |
ADAMTS3
HENNEKAM SYNDROME IN-SILICO NONSYNONYMOUS SNP PRIMARY IMMUNODEFICIENCY DIAGNOSIS GENES MOLECULAR DYNAMICS PATIENT TREATMENT RISK ASSESSMENT ADAMTS3 HENNEKAM SYNDROME IN-SILICO LYMPHOEDEMA NONSYNONYMOUS SNP PRIMARY IMMUNODEFICIENCY PROTEIN FUNCTIONS PROTEIN STABILITY SECONDARY STRUCTURES SINGLE NUCLEOTIDE POLYMORPHISMS PROTEINS BIOINFORMATICS GENETICS HUMAN LYMPHEDEMA MOLECULAR DYNAMICS PROTEIN STABILITY SINGLE NUCLEOTIDE POLYMORPHISM COMPUTATIONAL BIOLOGY HENNEKAM LYMPHANGIECTASIA LYMPHEDEMA SYNDROME HUMANS LYMPHEDEMA MOLECULAR DYNAMICS SIMULATION POLYMORPHISM, SINGLE NUCLEOTIDE PROTEIN STABILITY |
|
| Описание |
Hennekam Lymphangiectasia–Lymphedema Syndrome 3 (HKLLS3) is a rare genetical disorder caused by mutations in a few genes including ADAMTS3. It is characterized by lymphatic dysplasia, intestinal lymphangiectasia, severe lymphedema and distinctive facial appearance. Up till now, no extensive studies have been conducted to elucidate the mechanism of the disease caused by various mutations. As a preliminary investigation of HKLLS3, we sorted out the most deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) that might affect the structure and function of ADAMTS3 protein by using a variety of in silico tools. A total of 919 nsSNPs in the ADAMTS3 gene were identified. 50 nsSNPs were predicted to be deleterious by multiple computational tools. 5 nsSNPs (G298R, C567Y, A370T, C567R and G374S) were found to be the most dangerous and can be associated with the disease as predicted by different bioinformatics tools. Modelling of the protein shows it can be divided into segments 1, 2 and 3, which are connected by short loops. Segment 3 mainly consists of loops without substantial secondary structures. With prediction tools and molecular dynamics simulation, some SNPs were found to significantly destabilize the protein structure and disrupt the secondary structures, especially in segment 2. The deleterious effects of mutations in segment 1 are possibly not from destabilization but from other factors such as the change in phosphorylation as suggested by post-translational modification (PTM) studies. This is the first-ever study of ADAMTS3 gene polymorphism, and the predicted nsSNPs in ADAMST3, some of which have not been reported yet in patients, will serve for diagnostic purposes and further therapeutic implications in Hennekam syndrome, contributing to better diagnosis and treatment. © 2023, The Author(s).
Hong Kong University of Science and Technology, HKUST; Ural Branch, Russian Academy of Sciences, UB RAS; Ural Federal University, UrFU The authors would like to thank the Hong Kong University of Science and Technology, the Institute of Chemical Engineering in the Department of Immunochemistry of the Ural Federal University and the Ural Branch of the Russian Academy of Sciences for providing high-performance computers. |
|
| Дата |
2024-04-05T16:25:55Z
2024-04-05T16:25:55Z 2023 |
|
| Тип |
Article
Journal article (info:eu-repo/semantics/article) |info:eu-repo/semantics/publishedVersion |
|
| Идентификатор |
Shinwari, K, Wu, Y, Rehman, HM, Xiao, N, Bolkov, M, Tuzankina, I & Chereshnev, V 2023, 'In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function', BMC Bioinformatics, Том. 24, № 1, 251 (2023). https://doi.org/10.1186/s12859-023-05361-6
Shinwari, K., Wu, Y., Rehman, H. M., Xiao, N., Bolkov, M., Tuzankina, I., & Chereshnev, V. (2023). In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function. BMC Bioinformatics, 24(1), [251 (2023)]. https://doi.org/10.1186/s12859-023-05361-6 1471-2105 Final All Open Access, Gold, Green https://www.scopus.com/inward/record.uri?eid=2-s2.0-85162065984&doi=10.1186%2fs12859-023-05361-6&partnerID=40&md5=ef01076c1951ea816a468bee94be0005 https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-023-05361-6 http://elar.urfu.ru/handle/10995/130561 10.1186/s12859-023-05361-6 85162065984 001008701700001 |
|
| Язык |
en
|
|
| Права |
Open access (info:eu-repo/semantics/openAccess)
cc-by https://creativecommons.org/licenses/by/4.0/ |
|
| Формат |
application/pdf
|
|
| Издатель |
BioMed Central Ltd
|
|
| Источник |
BMC Bioinformatics
BMC Bioinformatics |
|