Novel high-risk missense mutations identification in FAT4 gene causing Hennekam syndrome and Van Maldergem syndrome 2 through molecular dynamics simulation
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
| Заглавие |
Novel high-risk missense mutations identification in FAT4 gene causing Hennekam syndrome and Van Maldergem syndrome 2 through molecular dynamics simulation
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| Автор |
Shinwari, K.
Rehman, H. M. Xiao, N. Guojun, L. Khan, M. A. Bolkov, M. A. Tuzankina, I. A. Chereshnev, V. A. |
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| Тематика |
DYNAMIC SIMULATION
FAT4 MISSENSE SNP HENNEKAM SYNDROME IN-SILICO PRIMARY IMMUNODEFICIENCY ADAMTS PROTEIN AMINO ACID CADHERIN FAT4 PROTEIN LAMININ MUTANT PROTEIN PEPTIDES AND PROTEINS UNCLASSIFIED DRUG VASCULOTROPIN C ALPHA HELIX AMINO ACID SEQUENCE ARTICLE AUTOSOMAL RECESSIVE DISORDER BETA SHEET CASE REPORT CHILD CLINICAL ARTICLE CLINICAL FEATURE COHORT ANALYSIS CRYSTAL STRUCTURE DISEASE PREDISPOSITION FEMALE GENE FREQUENCY GENE INTERACTION GENOTYPE HENNEKAM SYNDROME HUMAN HYDROPHOBICITY IMMUNE DEFICIENCY INDEL MUTATION LIGAND BINDING LYMPHADENOPATHY LYMPHANGIECTASIS LYMPHEDEMA MISSENSE MUTATION MOLECULAR DYNAMICS PATHOGENESIS PATHOGENICITY PHENOTYPE POINT MUTATION PREDICTION PRESCHOOL CHILD PROTEIN FUNCTION PROTEIN PHOSPHORYLATION PROTEIN SECONDARY STRUCTURE PROTEIN STABILITY PROTEIN STRUCTURE SANGER SEQUENCING SINGLE NUCLEOTIDE POLYMORPHISM UNITED STATES VAN MALDERGEM SYNDROME 2 WHOLE EXOME SEQUENCING |
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| Описание |
Hennekam syndrome (HS) is an autosomal recessive disease in the pathogenesis of which lymphangiectasia and lymphedema plays a key role. HS is associated with mutations in CCBE1, FAT4, and ADAMTS3 proteins that somehow affect the activation of the primary lymphangiogenic growth factor VEGF-C. We used several in silico methods to test this theory. According to NCBI, FAT4 gene contains 3,343 non-synonymous SNPs, of which 298 were predicted to be deleterious using SIFT and Polyphen2. These 298 SNPs were further studied using various mutation prediction tools. Our results showed that eleven nsSNPs (D2978G, V986D, Y1912C, R4799C, D1022G, G4786R, D2439E, E2426Q, R4643C, N1309I, and Y2909H) detected by these tools are deleterious. Additionally, three mutations in FAT4 gene (rs12650153, rs1567047, and rs1039808) in patient suspected with HS were discovered through candidate variant filtering of whole-exome sequencing, and in silico study of these mutations revealed that these are highly destabilizing the protein structure and function. Using molecular dynamics simulation (MDS) we focused on the mutations (11 mutations predicted by our insilco study, 3 reported in the patient and 5 already published mutations for HS and VMS), while one mutation (G4786R) was detected in the MPDZ domain. The RMSD and RMSF supports the destability of mutant protein compared to wild type. The mutations found in this cohort of studies have not previously been reported for HS. These mutations may contribute to better understanding of disease predisposition associated with FAT4 Cadherin-like domain activation and further aid to effective approaches for diagnosis and treatment of the disorder. © 2023
Ministry of Education and Science of the Russian Federation, Minobrnauka The research funding from the Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Program of Development within the Priority-2030 Program) is gratefully acknowledged. |
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| Дата |
2024-04-05T16:28:52Z
2024-04-05T16:28:52Z 2023 |
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| Тип |
Article
Journal article (info:eu-repo/semantics/article) |info:eu-repo/semantics/publishedVersion |
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| Идентификатор |
Shinwari, K, Rehman, HM, Xiao, N, Guojun, L, Khan, MA, Bolkov, MA, Tuzankina, IA & Chereshnev, VA 2023, 'Novel high-risk missense mutations identification in FAT4 gene causing Hennekam syndrome and Van Maldergem syndrome 2 through molecular dynamics simulation', Informatics in Medicine Unlocked, Том. 37, 101160. https://doi.org/10.1016/j.imu.2023.101160
Shinwari, K., Rehman, H. M., Xiao, N., Guojun, L., Khan, M. A., Bolkov, M. A., Tuzankina, I. A., & Chereshnev, V. A. (2023). Novel high-risk missense mutations identification in FAT4 gene causing Hennekam syndrome and Van Maldergem syndrome 2 through molecular dynamics simulation. Informatics in Medicine Unlocked, 37, [101160]. https://doi.org/10.1016/j.imu.2023.101160 2352-9148 Final All Open Access, Gold https://www.scopus.com/inward/record.uri?eid=2-s2.0-85146450575&doi=10.1016%2fj.imu.2023.101160&partnerID=40&md5=82221249a6f7fedeade27b9c5d43826e https://doi.org/10.1016/j.imu.2023.101160 http://elar.urfu.ru/handle/10995/130670 10.1016/j.imu.2023.101160 85146450575 |
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| Язык |
en
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| Права |
Open access (info:eu-repo/semantics/openAccess)
cc-by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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| Формат |
application/pdf
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| Издатель |
Elsevier Ltd
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| Источник |
Informatics in Medicine Unlocked
Informatics in Medicine Unlocked |
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