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Insights from the SNP analysis of TYMP gene linking MNGIE



Najat Sifeddine1,2,*, Lamiae Elkhattabi1, Chaimaa Ait El Cadi1, Al Mehdi Krami1, Khadija Mounaji2, Bouchra el khalfi2 & Abdelhamid Barakat*, 1



1Laboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, Casablanca, Morocco; 2Laboratory of Physiology and Molecular Genetics, Department of Biology, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca, Morocco; *Corresponding author



Najat Sifeddine - E-mail: sifeddinenajat30@gmail.com

Lamiae Elkhattabi -E-mail: lamiaeelkhattabi@gmail.com

Chaimaa Ait El Cadi - E-mail: chaimaa.aitelcadi-etu@etu.univh2c.ma

Al Mehdi Krami - E-mail: almehdi.krami@etu.univh2c.ma

Khadija Mounaji - E-mail: khadija.mounaji8@gmail.com

Bouchra el khalfi - E-mail: bouchra.elkhalfi@gmail.com


Article Type

Research Article



Received March 1, 2024; Revised March 31, 2024; Accepted March 31, 2024, Published March 31, 2024



TYMP gene, which codes for thymidine phosphorylase (TP) is also known as platelet-derived endothelial cell growth factor (PD-ECGF). TP plays crucial roles in nucleotide metabolism and angiogenesis. Mutations in the TYMP gene can lead to Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) syndrome, a rare genetic disorder. Our main objective was to evaluate the impact of detrimental non-synonymous single nucleotide polymorphisms (nsSNPs) on TP protein structure and predict harmful variants in untranslated regions (UTR). We employed a combination of predictive algorithms to identify nsSNPs with potential deleterious effects, followed by molecular modeling analysis to understand their effects on protein structure and function. Using 13 algorithms, we identified 119 potentially deleterious nsSNPs, with 82 located in highly conserved regions. Of these, 53 nsSNPs were functional and exposed, while 79 nsSNPs reduced TP protein stability. Further analysis of 18 nsSNPs through 3D protein structure analysis revealed alterations in amino acid interactions, indicating their potential impact on protein function. This will help in the development of faster and more efficient genetic tests for detecting TYMP gene mutations.



prediction; Mitochondrial Neurogastrointestinal Encephalopathy; Thymidine phosphorylase; nsSNPs; UTR; conservation; stability; molecular Modeling



Sifeddine et al. Bioinformation 20(3): 261-270 (2024)


Edited by

Peter N Pushparaj






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.