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CYP2R1 and CYP27A1 genes: An in silico approach to identify the deleterious mutations, impact on structure and their

Swetha Sunkar1, Desam Neeharika1

  • 1Center for Molecular Data science and Systems Biology, Department of Bioinformatics, Sathyabama Institute of Science and Technology, Chennai 119, India.

Genomics
|April 29, 2020
PubMed

Insights

Genetic variations in CYP2R1 and CYP27A1 impact Vitamin D metabolism. This study used computational methods to analyze mutations, revealing potential functional consequences and differential gene expression in diseases like cancer.

Area of Science:

  • Biochemistry
  • Genetics
  • Computational Biology

Background:

  • Vitamin D metabolism is crucial for health, involving the conversion of cholecalciferol to calcidiol.
  • Mutations in CYP2R1 and CYP27A1 genes impair this conversion, leading to altered 25-hydroxylase activity and affecting Vitamin D levels.
  • Understanding the impact of genetic variations on these enzymes is vital for comprehending Vitamin D-related disorders.

Purpose of the Study:

  • To investigate the influence of genetic variations in CYP2R1 and CYP27A1 on protein function using a computational approach.
  • To assess the pathogenicity, stability, and conservancy of non-synonymous mutations.
  • To explore the differential expression of these genes in various disease conditions.

Main Methods:

  • Utilized the dbSNP database to retrieve non-synonymous mutations.
  • Employed various computational tools to predict mutation pathogenicity, stability, and conservancy.
  • Performed protein structure modeling for native and mutant forms.
  • Analyzed protein-ligand interactions (cholecalciferol) using molecular modeling.
  • Investigated gene expression patterns using Gene Expression Omnibus (GEO) datasets.

Main Results:

  • Identified 11 out of 260 and 35 out of 489 non-synonymous mutations as deleterious in CYP2R1 and CYP27A1, respectively.
  • Modeled native and mutant protein structures, observing differences in hydrogen bonds, hydrophobic bonds, and binding affinities with cholecalciferol.
  • Found differential gene expression of CYP2R1 and CYP27A1 in cancer and arthritis samples compared to controls.

Conclusions:

  • Genetic variations in CYP2R1 and CYP27A1 can significantly influence Vitamin D metabolism by affecting enzyme function and protein interactions.
  • Deleterious mutations may alter protein stability and binding capabilities, potentially impacting Vitamin D levels.
  • Differential expression patterns suggest a role for these genes in the pathogenesis of diseases such as cancer and arthritis.
Keywords:
CYP27A1CYP2R1Differential expressionInteractionsModelingnsSNPs

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