TY - JOUR
T1 - In-silico identification of deleterious nonsynonymous SNPs of TBX1 gene
T2 - Functional and structural impact towards 22q11.2DS
AU - Almakhari, Maitha
AU - Chen, Yan
AU - Kong, Amanda Shen Yee
AU - Moradigaravand, Danesh
AU - Lai, Kok Song
AU - Lim, Swee Hua Erin
AU - Loh, Jiun Yan
AU - Maran, Sathiya
N1 - Publisher Copyright:
© 2024 Almakhari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2024/6
Y1 - 2024/6
N2 - The TBX1 gene plays a critical role in the development of 22q11.2 deletion syndrome (22q11.2DS), a complex genetic disorder associated with various phenotypic manifestations. In this study, we performed in-silico analysis to identify potentially deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) within the TBX1 gene and evaluate their functional and structural impact on 22q11.2DS. A comprehensive analysis pipeline involving multiple computational tools was employed to predict the pathogenicity of nsSNPs. This study assessed protein stability and explored potential alterations in protein-protein interactions. The results revealed the rs751339103(C>A), rs780800634(G>A), rs1936727304(T>C), rs1223320618(G>A), rs1248532217(T>C), rs1294927055 (C>T), rs1331240435 (A>G, rs1601289406 (A>C), rs1936726164 (G>A), and rs911796187(G>A) with a high-risk potential for affecting protein function and stability. These nsSNPs were further analyzed for their impact on post-translational modifications and structural characteristics, indicating their potential disruption of molecular pathways associated with TBX1 and its interacting partners. These findings provide a foundation for further experimental studies and elucidation of potential therapeutic targets and personalized treatment approaches for individuals affected by 22q11.2DS.
AB - The TBX1 gene plays a critical role in the development of 22q11.2 deletion syndrome (22q11.2DS), a complex genetic disorder associated with various phenotypic manifestations. In this study, we performed in-silico analysis to identify potentially deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) within the TBX1 gene and evaluate their functional and structural impact on 22q11.2DS. A comprehensive analysis pipeline involving multiple computational tools was employed to predict the pathogenicity of nsSNPs. This study assessed protein stability and explored potential alterations in protein-protein interactions. The results revealed the rs751339103(C>A), rs780800634(G>A), rs1936727304(T>C), rs1223320618(G>A), rs1248532217(T>C), rs1294927055 (C>T), rs1331240435 (A>G, rs1601289406 (A>C), rs1936726164 (G>A), and rs911796187(G>A) with a high-risk potential for affecting protein function and stability. These nsSNPs were further analyzed for their impact on post-translational modifications and structural characteristics, indicating their potential disruption of molecular pathways associated with TBX1 and its interacting partners. These findings provide a foundation for further experimental studies and elucidation of potential therapeutic targets and personalized treatment approaches for individuals affected by 22q11.2DS.
UR - http://www.scopus.com/inward/record.url?scp=85196823042&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0298092
DO - 10.1371/journal.pone.0298092
M3 - Article
C2 - 38905172
AN - SCOPUS:85196823042
SN - 1932-6203
VL - 19
JO - PloS one
JF - PloS one
IS - 6 June
M1 - e0298092
ER -