Revisiting the Effects of MDR1 Variants Using Computational Approaches

Tal Gutman, Tamir Tuller*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

P-glycoprotein, encoded by the MDR1 gene, is an ATP-dependent pump that exports various substances out of cells. Its overexpression is related to multi drug resistance in many cancers. Numerous studies explored the effects of MDR1 variants on p-glycoprotein expression and function, and on patient survivability. T1236C, T2677G and T3435C are prevalent MDR1 variants that are the most widely studied, typically in-vitro and in-vivo, with remarkably inconsistent results. In this paper we perform computational, data-driven analyses to assess the effects of these variants using a different approach. We use knowledge of gene expression regulation to elucidate the variants’ mechanism of action. Results indicate that T1236C is correlated with worse patient prognosis. Additionally, examination of MDR1 folding strength suggests that T3435C potentially modifies co-translational folding. Furthermore, all three variants reside in potential translation bottlenecks and likely cause increased translation rates. These results support several hypotheses suggested by previous studies. To the best of our knowledge, this study is the first to apply a computational approach to examine the effects of MDR1 variants.

Original languageEnglish
Title of host publicationComparative Genomics - 21st International Conference, RECOMB-CG 2024, Proceedings
EditorsCeline Scornavacca, Maribel Hernández-Rosales
PublisherSpringer Science and Business Media Deutschland GmbH
Pages226-247
Number of pages22
ISBN (Print)9783031580710
DOIs
StatePublished - 2024
Event21st RECOMB International Workshop on Comparative Genomics, RECOMB-CG 2024 - Boston, United States
Duration: 27 Apr 202428 Apr 2024

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume14616 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

Conference21st RECOMB International Workshop on Comparative Genomics, RECOMB-CG 2024
Country/TerritoryUnited States
CityBoston
Period27/04/2428/04/24

Keywords

  • MDR1
  • cancer evolution
  • gene expression
  • mRNA folding selection
  • synonymous variants

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