In Silico Functional and Structural Analysis of Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in Human Paired Box 4 Gene
In human genome, members of Paired box (PAX) transcription factor family are highly sequence-specific DNA-binding proteins. Among PAX gene family members, PAX4 gene has significant role in growth, proliferation, differentiation, and insulin secretion of pancreatic β-cells. Single nucleotide polymorp...
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Veröffentlicht in: | Biochemical genetics 2024-08, Vol.62 (4), p.2975-2998 |
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Zusammenfassung: | In human genome, members of Paired box (PAX) transcription factor family are highly sequence-specific DNA-binding proteins. Among
PAX
gene family members,
PAX4
gene has significant role in growth, proliferation, differentiation, and insulin secretion of pancreatic β-cells. Single nucleotide polymorphisms (SNPs) in
PAX4
gene progress in the pathogenesis of various human diseases. Hence, the molecular mechanism of how these SNPs in
PAX4
gene significantly progress diseases pathogenesis needs to be elucidated. For the reason, a series of bioinformatic analyzes were done to identify the SNPs of
PAX4
gene that contribute in diseases pathogenesis. From the analyzes, 4145 SNPs (rsIDs) in
PAX4
gene were obtained, where, 362 missense (8.73%), 169 synonymous (4.08%), and 2323 intron variants (56.04%). The rest SNPs were unspecified. Among the 362 missense variants, 118 nsSNPs were found as deleterious in SIFT analysis. Among those, 25 nsSNPs were most probably damaging and 23 were deleterious as observed in PolyPhen-2 and PROVEAN analyzes, respectively. Following all analyzes, 14 nsSNPs (rs149708455, rs115887120, rs147279315, rs35155575, rs370095957, rs373939873, rs145468905, rs121917718, rs2233580, rs3824004, rs372751660, rs369459316, rs375472849, rs372497946) were common and observed as deleterious, probably damaging, affective and diseases associated. Following structural analyzes, 11 nsSNPs guided proteins were found as most unstable and highly conserved. Among these, R20W, R39Q, R45Q, R60H, G65D, and A223D mutated proteins were highly harmful. Hence, the results from above-mentioned integrated comprehensive bioinformatic analyzes guide how different nsSNPs in
PAX4
gene alter structural and functional characteristics of the protein that might progress diseases pathogenesis in human including type 2 diabetes. |
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ISSN: | 0006-2928 1573-4927 1573-4927 |
DOI: | 10.1007/s10528-023-10589-1 |