Related Experiment Video
Updated: Apr 8, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
In silico analysis of functional nsSNPs in human TRPC6 gene associated with steroid resistant nephrotic syndrome
Bhoomi B Joshi1, Prakash G Koringa2, Kinnari N Mistry1
1Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), affiliated to Sardar Patel University, Vallabh Vidyanagar, Gujarat 388120, India.
Abstract:
The aim of the present study is to identify functional non-synonymous SNPs of TRPC6 gene using various in silico approaches. These SNPs are believed to have a direct impact on protein stability through conformation changes. Transient receptor potential cation channel-6 (TRPC6) is one of the proteins that plays a key role causing focal segmental glomerulosclerosis (FSGS) associated with the steroid-resistant nephritic syndrome (SRNS). Data of TRPC6 was collected from dbSNP and further used to investigate a damaging effect using SIFT, PolyPhen, PROVEAN, and PANTHER. The comparative analysis predicted that two functional SNPs "rs35857503 at position N157T and rs36111323 at position A404V" showed a damaging effect (score of 0.096-1.00).We modeled the 3D structure of TRPC6 using a SWISS-MODEL workspace and validated it via PROCHECK to get a Ramachandran plot (83.0% residues in the most favored region, 12.7% in additionally allowed regions, 2.3% in a generously allowed region and 2.0% were in a disallowed region). QMEAN (0.311) and MUSTER (10.06) scores were under acceptable limits. Putative functional SNPs that may possibly undergo post-translation modifications were also identified in TRPC6 protein. It was found that mutation at N157T can lead to alteration in glycation whereas mutation at A404V was present at a ligand binding site. Additionally, I-Mutant showed a decrease in stability for these nsSNPs upon mutation, thus suggesting that the N157T and A404V variants of TRPC6 could directly or indirectly destabilize the amino acid interactions causing functional deviations of protein to some extent.
More Related Videos
16:02Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
12:19Single-channel Analysis and Calcium Imaging in the Podocytes of the Freshly Isolated Glomeruli
Published on: June 27, 2015
Related Concept Videos
Pharmacogenomics: Identification of New Drug Targets
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Single Nucleotide Polymorphisms-SNPs
Principles of Pharmacogenetics: Types of Genetic Variants