Research Article

DOI :10.26650/experimed.1562959 IUP :10.26650/experimed.1562959 Full Text (PDF)

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

Aslı Kutlu, Begüm Işıkgil, Sinem Fırtına

Objective: Primary immune deficiencies (PIDs) are syndromic diseases characterized by severe clinical findings 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.

Keywords: Primer immune deficiency, Severe combined immunodeficiency, Omenn syndrome, Atypical SCID, RAG1 gene, Structural alterations

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APA

Kutlu, A., Işıkgil, B., & Fırtına, S. (2020). Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective. Experimed, 0(0), -. https://doi.org/10.26650/experimed.1562959

AMA

Kutlu A, Işıkgil B, Fırtına S. Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective. Experimed. 2020;0(0):-. https://doi.org/10.26650/experimed.1562959

ABNT

Kutlu, A.; Işıkgil, B.; Fırtına, S. Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective. Experimed, [Publisher Location], v. 0, n. 0, p. -, 2020.

Chicago: Author-Date Style

Kutlu, Aslı, and Begüm Işıkgil and Sinem Fırtına. 2020. “Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective.” Experimed 0, no. 0: -. https://doi.org/10.26650/experimed.1562959

Chicago: Humanities Style

Kutlu, Aslı, and Begüm Işıkgil and Sinem Fırtına. “Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective.” Experimed 0, no. 0 (Apr. 2025): -. https://doi.org/10.26650/experimed.1562959

Harvard: Australian Style

Kutlu, A & Işıkgil, B & Fırtına, S 2020, 'Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective', Experimed, vol. 0, no. 0, pp. -, viewed 3 Apr. 2025, https://doi.org/10.26650/experimed.1562959

Harvard: Author-Date Style

Kutlu, A. and Işıkgil, B. and Fırtına, S. (2020) ‘Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective’, Experimed, 0(0), pp. -. https://doi.org/10.26650/experimed.1562959 (3 Apr. 2025).

MLA

Kutlu, Aslı, and Begüm Işıkgil and Sinem Fırtına. “Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective.” Experimed, vol. 0, no. 0, 2020, pp. -. [Database Container], https://doi.org/10.26650/experimed.1562959

Vancouver

Kutlu A, Işıkgil B, Fırtına S. Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective. Experimed [Internet]. 3 Apr. 2025 [cited 3 Apr. 2025];0(0):-. Available from: https://doi.org/10.26650/experimed.1562959 doi: 10.26650/experimed.1562959

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Kutlu, Aslı - Işıkgil, Begüm - Fırtına, Sinem. “Contributing to the Functional Classification of Missense Variants in RAG1 Protein from Structural Perspective”. Experimed 0/0 (Apr. 2025): -. https://doi.org/10.26650/experimed.1562959

TIMELINE

Submitted	08.10.2024
Accepted	04.02.2025
Published Online	13.03.2025

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