Please use this identifier to cite or link to this item: http://hdl.handle.net/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://hdl.handle.net/10995/111176
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85110945714
PURE ID: 22974012
ISSN: 2356-6140
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, проиндексированные в SCOPUS и WoS CC

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