# Insights from the SNP analysis of TYMP gene linking MNGIE

## TL;DR

This study analyzes TYMP gene mutations linked to MNGIE syndrome, identifying harmful SNPs that affect protein structure and function.

## Contribution

The study introduces a novel approach combining predictive algorithms and 3D modeling to identify harmful TYMP gene variants.

## Key findings

- 119 potentially deleterious nsSNPs were identified, with 82 in highly conserved regions.
- 79 nsSNPs were found to reduce TP protein stability.
- 3D analysis of 18 nsSNPs revealed altered amino acid interactions affecting protein function.

## Abstract

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.