Impact of nsSNPs in human AIM2 and IFI16 gene: a comprehensive in silico analysis

Abstract

AIM2 and IFI16 are the most studied members of AIM2-like receptors (ALRs) in humans and share a common N-Terminal PYD domain and C-terminal HIN domain. The HIN domain binds to dsDNA in response to the invasion of bacterial and viral DNA, and the PYD domain directs apoptosis-associated speck-like protein via protein–protein interactions. Hence, activation of AIM2 and IFI16 is crucial for protection against pathogenic assaults, and any genetic variation in these inflammasomes can dysregulate the human immune system. In this study, different computational tools were used to identify the most deleterious and disease-causing non-synonymous single nucleotide polymorphisms (nsSNPs) in AIM2 and IFI16 proteins. Molecular dynamic simulation was performed for the top damaging nsSNPs to study single amino acid substitution-induced structural alterations in AIM2 and IFI16. The observed results suggest that the variants G13V, C304R, G266R, and G266D for AIM2, and G13E and C356F are deleterious and affect structural integrity. We hope that the suggested deleterious nsSNPs and structural dynamics of AIM2 and IFI16 variants will guide future research to better understand the function of these variants with large-scale studies and may assist in fresher therapeutics focusing on these polymorphisms.

Communicated by Ramaswamy H. Sarma

Keywords:

• Single nucleotide polymorphism
• AIM2
• IFI16
• SIFT
• molecular dynamics
• conservation

Authors’ contributions

Conceptualization: V.G.; formal analysis: S.S. and S.S; investigation: S.S.; supervision: D.S.; Writing—original draft: S.S., and V.G.; Writing—review and editing: H.L., J.L., V.G., and D.S.

Disclosure statement

There are no conflicts to declare.

Additional information

Funding

This study was funded by the National Research Foundation of Korea (Grant Numbers NRF-2018R1C1B6008141 and 2022R1A2C4002510).