In-silico investigation of p. Pro۱۲۳Arg missense mutation in the SOCS۱ gene and its effect on the development and appearance of tumorigenesis

Introduction Suppressor of Cytokine Signaling ۱ (SOCS۱) is a crucial regulator of cytokine signaling, particularly within the JAK/STAT pathway. SOCS۱ functions as a negative feedback regulator, ensuring that cytokine signaling is appropriately controlled to prevent overactivation of immune responses. This protein contains essential domains, including the SH۲ domain, responsible for binding to phosphorylated tyrosine residues on cytokine receptors, and the Kinase Inhibitory Region (KIR), which directly inhibits JAK activity. Proper functioning of SOCS۱ is vital for maintaining immune homeostasis and preventing excessive inflammatory responses that can lead to tissue damage and autoimmune disorders. Dysregulation of SOCS۱ has been implicated in various pathological conditions, including chronic inflammation and cancer. Materials and Methods This study examines the functional consequences of mutations in the SOCS۱ gene, with a specific focus on the p.Pro۱۲۳Arg variant located in the SH۲ domain, which is essential for SOCS۱'s activity. The SH۲ domain allows SOCS۱ to bind to cytokine receptors and inhibit JAK activity. The research analyzes these mutations and their impacts on the structure and function of the protein. Results Analysis indicates that the p.Pro۱۲۳Arg mutation significantly compromises protein stability. The MUpro tool predicts a decrease in protein stability, reporting a confidence score of -۰.۳۸. The HOPE tool suggests that this mutation introduces a new charge at the specified position, potentially disrupting essential hydrophobic interactions. Additionally, SIFT analysis indicates that the mutation adversely affects protein function, yielding a score of ۰.۰۲, while PolyPhen-۲ classifies it as "probably damaging" with a score of ۰.۹۹۹. Conclusion Dysregulation of SOCS۱ due to such mutations is significant, as it may intensify inflammatory responses and contribute to the development of autoimmune diseases and various cancers, including hepatocellular carcinoma and lymphoid malignancies. This research highlights the necessity of understanding SOCS۱ mutations and their implications for targeted therapeutic strategies aimed at restoring SOCS۱ function. Future investigations should focus on exploring these therapeutic approaches to mitigate the detrimental effects associated with SOCS۱ dysregulation.

کلیدواژه ها:

Missense variant ، Bioinformatic analysis ، Tumorigenesis ، Cancer