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http://elar.urfu.ru/handle/10995/111176
Title: | Predicting the Most Deleterious Missense Nonsynonymous Single-Nucleotide Polymorphisms of Hennekam Syndrome-Causing CCBE1 Gene, in Silico Analysis |
Authors: | Shinwari, K. Guojun, L. Deryabina, S. S. Bolkov, M. A. Tuzankina, I. A. Chereshnev, V. A. |
Issue Date: | 2021 |
Publisher: | Hindawi Limited Hindawi Limited |
Citation: | Predicting the Most Deleterious Missense Nonsynonymous Single-Nucleotide Polymorphisms of Hennekam Syndrome-Causing CCBE1 Gene, in Silico Analysis / K. Shinwari, L. Guojun, S. S. Deryabina et al. // Scientific World Journal. — 2021. — Vol. 2021. — 6642626. |
Abstract: | Hennekam lymphangiectasia-lymphedema syndrome has been linked to single-nucleotide polymorphisms in the CCBE1 (collagen and calcium-binding EGF domains 1) gene. Several bioinformatics methods were used to find the most dangerous nsSNPs that could affect CCBE1 structure and function. Using state-of-the-art in silico tools, this study examined the most pathogenic nonsynonymous single-nucleotide polymorphisms (nsSNPs) that disrupt the CCBE1 protein and extracellular matrix remodeling and migration. Our results indicate that seven nsSNPs, rs115982879, rs149792489, rs374941368, rs121908254, rs149531418, rs121908251, and rs372499913, are deleterious in the CCBE1 gene, four (G330E, C102S, C174R, and G107D) of which are the highly deleterious, two of them (G330E and G107D) have never been seen reported in the context of Hennekam syndrome. Twelve missense SNPs, rs199902030, rs267605221, rs37517418, rs80008675, rs116596858, rs116675104, rs121908252, rs147974432, rs147681552, rs192224843, rs139059968, and rs148498685, are found to revert into stop codons. Structural homology-based methods and sequence homology-based tools revealed that 8.8% of the nsSNPs are pathogenic. SIFT, PolyPhen2, M-CAP, CADD, FATHMM-MKL, DANN, PANTHER, Mutation Taster, LRT, and SNAP2 had a significant score for identifying deleterious nsSNPs. The importance of rs374941368 and rs200149541 in the prediction of post-translation changes was highlighted because it impacts a possible phosphorylation site. Gene-gene interactions revealed CCBE1's association with other genes, showing its role in a number of pathways and coexpressions. The top 16 deleterious nsSNPs found in this research should be investigated further in the future while researching diseases caused CCBE1 gene specifically HS. The FT web server predicted amino acid residues involved in the ligand-binding site of the CCBE1 protein, and two of the substitutions (R167W and T153N) were found to be involved. These highly deleterious nsSNPs can be used as marker pathogenic variants in the mutational diagnosis of the HS syndrome, and this research also offers potential insights that will aid in the development of precision medicines. CCBE1 proteins from Hennekam syndrome patients should be tested in animal models for this purpose. © 2021 Khyber Shinwari et al. |
Keywords: | ARGININE CALCIUM BINDING PROTEIN COLLAGEN AND CALCIUM BINDING DOMAIN 1 COLLAGEN BINDING PROTEIN CYSTEINE GLUTAMIC ACID GLYCINE SERINE TRYPTOPHAN UNCLASSIFIED DRUG CCBE1 PROTEIN, HUMAN TUMOR SUPPRESSOR PROTEIN ADULT AMINO ACID SEQUENCE AMINO ACID SUBSTITUTION ANIMAL EXPERIMENT ANIMAL MODEL ARTICLE BINDING SITE BIOINFORMATICS CELL MIGRATION COMPUTER MODEL CONFORMATIONAL TRANSITION CONTROLLED STUDY EXTRACELLULAR MATRIX FEMALE GENE FREQUENCY GENE INTERACTION GENETIC ALGORITHM GENETIC ASSOCIATION HENNEKAM SYNDROME LIGAND BINDING MALE MISSENSE MUTATION MOLECULAR DIAGNOSIS NONHUMAN PROTEIN GLYCOSYLATION PROTEIN PHOSPHORYLATION PROTEIN SECONDARY STRUCTURE PROTEIN STABILITY SEQUENCE HOMOLOGY SINGLE NUCLEOTIDE POLYMORPHISM STOP CODON STRUCTURAL HOMOLOGY SYNDROME BIOLOGY CRANIOFACIAL MALFORMATION GENETICS INTESTINE LYMPHANGIECTASIA CALCIUM-BINDING PROTEINS COMPUTATIONAL BIOLOGY CRANIOFACIAL ABNORMALITIES FORECASTING HUMANS LYMPHANGIECTASIS, INTESTINAL LYMPHEDEMA MUTATION, MISSENSE POLYMORPHISM, SINGLE NUCLEOTIDE |
URI: | http://elar.urfu.ru/handle/10995/111176 |
Access: | info:eu-repo/semantics/openAccess |
SCOPUS ID: | 85110945714 |
PURE ID: | 22974012 |
ISSN: | 2356-6140 |
DOI: | 10.1155/2021/6642626 |
metadata.dc.description.sponsorship: | The work was carried out within the framework of state research at the Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, project number AAAA-A21-121012090091-6. |
Appears in Collections: | Научные публикации ученых УрФУ, проиндексированные в SCOPUS и WoS CC |
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