Computational Protein Phenotype Characterization of IL10RA Mutations Causative to Early Onset Inflammatory Bowel Disease (IBD)

Frontiers in Genetics
Fahad A Al-AbbasiNoor A Shaik

Abstract

The deleterious amino acid substitution mutations in IL-10 receptor alpha gene are most frequently reported in several autoimmune diseases including early onset-inflammatory bowel disease (IBD). Despite the important role of IL-10 RA in maintaining immune homeostasis, the specific structural and functional implications of these mutations on protein phenotype, stability, ligand binding and post translational characteristics is not well explored. Therefore, this study performed the multidimensional computational analysis of IL10RA missense variations causative to pediatric or early onset inflammatory bowel disease (<5 years of age). Our computational algorithmic screening identified the deleterious nature of p. W45G, p. Y57C, p. W69G, p.T84I, p.Y91C, p.R101W, p.R117C, and p.R117H, IBD causative IL10-RA mutations. The sensitivity and specificity analysis of different computational methods showed that CADD outperform SIFT, PolyPhen 2.0, FATHMM, LRT, MetaLR, MetaSVM, PROVEAN and Condel in predicting the pathogenicity of IL10RA mutations. Our three-dimensional protein modeling assays showed that the point mutations cause major drifts in the structural plasticity of IL10 RA molecule and negatively influence its stability. Findings fro...Continue Reading

References

Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A S HoK W Moore
Dec 1, 1995·Computer Methods and Programs in Biomedicine·F SchoonjansF H Comhaire
Mar 28, 1998·The Journal of Experimental Medicine·S D SpencerM Aguet
Nov 6, 2009·The New England Journal of Medicine·Erik-Oliver GlockerChristoph Klein
Apr 27, 2011·The American Journal of Gastroenterology·Bernadette BegueFrank M Ruemmele
May 3, 2012·Inflammatory Bowel Diseases·Christopher J MoranAleixo M Muise
Nov 20, 2012·The Journal of Allergy and Clinical Immunology·Karin R EngelhardtErik-Oliver Glocker
Jul 11, 2013·European Journal of Gastroenterology & Hepatology·Jung Ok ShimJeong Kee Seo
May 13, 2014·Journal of Crohn's & Colitis·Cheng Hiang LeeMichael O Stormon
Nov 7, 2014·Journal of Pediatric Gastroenterology and Nutrition·Omer Faruk BeşerTülay Erkan
Dec 31, 2014·Nature Methods·Jianyi YangYang Zhang
Jan 28, 2016·Journal of Cellular Biochemistry·Babajan BanaganapalliNoor Ahmad Shaik
Jun 9, 2016·Genome Biology·William McLarenFiona Cunningham
Jan 7, 2017·Journal of Cellular Biochemistry·Babajan BanaganapalliRamu Elango
Mar 24, 2017·Journal of Crohn's & Colitis·Kaleemuddin MohammedFahad Ahmed Al-Abbasi
May 13, 2017·Gastroenterology Research·Lei ZhuXiuli Liu
Jun 29, 2017·Nature·Hailiang HuangJeffrey C Barrett

❮ Previous
Next ❯

Citations

Sep 24, 2019·Journal of Biomolecular Structure & Dynamics·Noor A ShaikBabajan Banaganapalli
Jul 1, 2020·Journal of Biomolecular Structure & Dynamics·Khalidah Khalid NasserNoor Ahmad Shaik

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear translocation
NMR
X-ray

Software Mentioned

PolyPhen
MetaSVM
PSI
SIFT
CADD
Ensemble VEP ( Variant Effect Predictor )
Exome Variant Server
Condel
MetaLR
Swiss Model - Expasy

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.