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Journals / Experimed / 2026 / Volume: 15 Issue: 1

Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective

Aslı Kutlu(Istinye University, Faculty of Engineering and Natural Science, Department of Molecular Biology and Genetics)0000-0002-9169-388X
Begüm Işıkgil(Istinye University, Faculty of Engineering and Natural Science, Department of Molecular Biology and Genetics)0000-0002-7541-4596
Sinem Firtina(ISTANBUL UNIVERSITY-CERRAHPASA, CERRAHPAŞA SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL GENETICS)0000-0002-3370-8545
Journal
Experimed
Pages
—
Publication Date
2025-04-16
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Conclusions: The utilization of in-silico computational tools provides a great advantage to gain insight about variant specific molecular mechanisms of diseases to boost existing knowledge about RAG1/2 failures.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: Primary immune deficiencies (PIDs) are syndromic diseases characterized by severe clinical f indings in early childhood.
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Key Findings & Data:The failures in variable, diversity, joining (V(D)J) recombination, which are also controlled by the recombination activating gene (RAG) 1/2 complex, result in the deficiency of B- and T-cells, and these failures are associated with SCID or its alternative forms.
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Conclusion & Impact:Conclusions: The utilization of in-silico computational tools provides a great advantage to gain insight about variant specific molecular mechanisms of diseases to boost existing knowledge about RAG1/2 failures.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Primer immune deficiency · Severe combined immunodeficiency · Omenn syndrome

Abstract

Objective: Primary immune deficiencies (PIDs) are syndromic diseases characterized by severe clinical f indings in early childhood. The diagnosis and treatment of PID are challenging due to its genetic and clinical heterogeneity. Severe combined immune deficiency (SCID) is one of its most severe and fatal forms and is characterized by the absence of T lymphocytes and either the presence of B and/or natural killer (NK) cells. The failures in variable, diversity, joining (V(D)J) recombination, which are also controlled by the recombination activating gene (RAG) 1/2 complex, result in the deficiency of B- and T-cells, and these failures are associated with SCID or its alternative forms. Due to complete defect in RAG1 function, the SCID phenotype occurs, but OMENN syndrome (OS) and atypic SCID (AS) occur if defects in RAG1 function are partially tolerated. Materials and Methods: By using in-silico computational tools, the structural differences are revealed and then variants are prioritized according to how degree the existing structural alterations are tolerated or not. Results: These promising ones are Arg474Cys, Arg778Gln & Arg975Trp in AS, Arg396His, Arg396Leu, Arg624Cys, Trp552Cys, Val433Met & Met435Val in OS, and Arg474His and Glu722Lys in SCID. Conclusions: The utilization of in-silico computational tools provides a great advantage to gain insight about variant specific molecular mechanisms of diseases to boost existing knowledge about RAG1/2 failures.

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Cite This Article

Kutlu, A., Işıkgil, B., Firtina, S. (2025). Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective. Experimed, Volume: 15 Issue: 1. https://doi.org/10.26650/experimed.1562959

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