Bioinformatic Analysis of a Missense Mutationin the SOCS۳ Gene Associated with Acute LymphoblasticLeukemia (ALL) and Prediction of its Pathogenesis

سال انتشار: 1402
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 92

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شناسه ملی سند علمی:

CGC01_184

تاریخ نمایه سازی: 29 آبان 1402

چکیده مقاله:

Introduction: Acute lymphoblastic leukemia is a hematologicalmalignancy and includes the proliferation of immaturelymphoid cells in the bone marrow and peripheral blood. Thehighest incidence of acute lymphoblastic leukemia is in children Members of the SOCS (suppressor of cytokine signaling)protein family include SOCS۱-SOCS۷ and CIS (cytokinecontainingSH۲ protein). The structure of these eight proteinsconsists of a variable N-terminal domain, an SH۲ domain, anda C-terminal SOCS box. The SOCS۳ gene is located on humanchromosome ۱۷q۲۵.۳ and its protein has ۲۲۵ amino acids anda molecular weight of ۲۴.۷ kDa. SOCS۳ protein plays an inhibitoryrole in the Jak۲/STAT۳ signaling pathway and controlsinflammatory and immune responses. SOCS۳ protein has a motifcalled KIR (kinase inhibitory region), which inhibits JAK۲activity. SOCS۳ gene transcription is induced by type I and IIcytokines that signal through STAT۱ or STAT۳.Materials and Methods: In this study, we reviewedrs۷۴۸۸۵۸۳۶۳ by PolyPhen-۲, I-Mutant, SNPs & GO, and Hopeservers.Results: By polyphen-۲ data we found that this mutation isprobably damaging and I-Mutant showed that the T۱۹۶I mutationof SOCS۳ could decrease SOCS۳ protein resistance. SNPs& GO showed the probability and association of the diseasecaused by this mutation. Hope Server results showed that thismutation is structurally located in the SOCS box domain. Themutation introduces an amino acid with different properties,which can disturb this domain and abolish its function. Themutated residue is larger, this may lead to bulges. The mutantresidue is more hydrophobic than the wild-type residue. Themutation introduces a more hydrophobic residue at this position,which can result in the loss of hydrogen bonds or disruptionof proper folding.Conclusion: In this article, we analyzed a specific mutationwith rs۷۴۸۸۵۸۳۶۳, which causes the conversion of nucleotideC to T at position ۵۸۷, resulting in the amino acid Threonineat position ۱۹۶ becoming an amino acid Isoleucine converted.We used several bioinformatics tools to analyze this mutation,which shows that this mutation reduces protein stability andpossibly causes disease. However, in vitro and in vivo testsshould be used to prove that it is pathogenic.

نویسندگان

Marzie Nemati Shams Abad

Department of Biology, Yazd University, Yazd, Iran

Mehri Khatami

Department of Biology, Yazd University, Yazd, Iran