An integrative analysis of functional consequences of PKD2 missense variants on RNA and protein structures: a computational approach DOI Creative Commons
Chandra Devi, Prashant Ranjan, Parimal Das

et al.

Egyptian Journal of Medical Human Genetics, Journal Year: 2024, Volume and Issue: 25(1)

Published: Nov. 8, 2024

The PKD2, encoding polycystin-2 (PC2) protein, is second major genetic determinant of autosomal dominant polycystic kidney disease (ADPKD) after PKD1. However, the structural and functional consequences variants in PKD2 remain poorly understood. Given complexity heterogeneous nature ADPKD, understanding its pathogenesis at cellular molecular levels vital for deciphering genotype–phenotype correlations severity, thus informing patient-centered treatments. We analyzed missense to assess their impact on RNA structure using computational tools explored associated protein dynamics through MD simulation. Our findings reveal distinct alterations dynamic behaviors with specific variants. such as c.1789C > A (p.L597M), c.1109G (p.S370N), c.1849C (p.L617I), c.646 T C (p.Y216H) induced changes not only accessibility profile but also dynamics. In contrast, c.915C (p.N305K), c.1354A G (p.I452V), c.568G (p.A190T) resulted minor exhibited noticeable effects certain parameters This study suggests multifaceted these both levels. It lays groundwork identifying high-impact terms pathogenicity prioritizing further implications heterogeneity eventually contributing development targeted therapeutic interventions ADPKD.

Language: Английский

An integrative analysis of functional consequences of PKD2 missense variants on RNA and protein structures: a computational approach DOI Creative Commons
Chandra Devi, Prashant Ranjan, Parimal Das

et al.

Egyptian Journal of Medical Human Genetics, Journal Year: 2024, Volume and Issue: 25(1)

Published: Nov. 8, 2024

The PKD2, encoding polycystin-2 (PC2) protein, is second major genetic determinant of autosomal dominant polycystic kidney disease (ADPKD) after PKD1. However, the structural and functional consequences variants in PKD2 remain poorly understood. Given complexity heterogeneous nature ADPKD, understanding its pathogenesis at cellular molecular levels vital for deciphering genotype–phenotype correlations severity, thus informing patient-centered treatments. We analyzed missense to assess their impact on RNA structure using computational tools explored associated protein dynamics through MD simulation. Our findings reveal distinct alterations dynamic behaviors with specific variants. such as c.1789C > A (p.L597M), c.1109G (p.S370N), c.1849C (p.L617I), c.646 T C (p.Y216H) induced changes not only accessibility profile but also dynamics. In contrast, c.915C (p.N305K), c.1354A G (p.I452V), c.568G (p.A190T) resulted minor exhibited noticeable effects certain parameters This study suggests multifaceted these both levels. It lays groundwork identifying high-impact terms pathogenicity prioritizing further implications heterogeneity eventually contributing development targeted therapeutic interventions ADPKD.

Language: Английский

Citations

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