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Impact of coding and non-coding SNPs in the FZD8 gene on structural and functional alterations associated with

Amalesh Mondal1, Debarati Paul2, Tithi Mondal3

  • 1Department of Physiology, Katwa College, Katwa, Purba Bardhaman, West Bengal, 713130, India.

Computers in Biology and Medicine
|February 25, 2026
PubMed

Insights

This study identifies high-risk FZD8 gene SNPs affecting protein structure and function, potentially driving tumorigenesis. These findings offer insights into cancer development and potential therapeutic targets for FZD8-associated diseases.

Area of Science:

  • Genetics
  • Bioinformatics
  • Molecular Biology

Background:

  • Frizzled-8 (FZD8) is a G protein-coupled receptor crucial for Wnt signaling, involved in cell differentiation and development.
  • Aberrant Wnt/FZD signaling contributes to tumorigenesis, yet the impact of FZD8 genetic variations remains largely unexplored.

Purpose of the Study:

  • To computationally analyze single nucleotide polymorphisms (SNPs) in the FZD8 gene for their structural and functional effects on tumorigenesis.
  • To identify deleterious FZD8 SNPs and assess their impact on protein function, stability, and Wnt1 binding.

Main Methods:

  • Bioinformatic analysis of 450 CDS, 109 3'UTR, and 390 5'UTR SNPs in the FZD8 gene.
  • Prediction of SNP structural and functional consequences, including effects on post-translational modifications and mRNA stability.
  • Molecular dynamics (MD) simulations to evaluate the impact of nsSNPs on Wnt1-FZD8 complex stability.

Main Results:

  • Identified 10 highly deleterious non-synonymous SNPs (nsSNPs), with 6 located in the Wnt1 binding region.
  • Predicted nsSNPs affect post-translational modifications and mRNA stability, with P120Q causing significant structural changes.
  • MD simulations indicated reduced stability for mutated Wnt1-FZD8 complexes, particularly P74L and A119E.
  • Identified SNPs potentially influencing gene silencing via AGO2, E2F6, and miRNA pathways.
  • Observed differential FZD8 expression in tumors, associated with poorer survival and identified as biomarkers in gastric cancer, multiple myeloma, and uterine cancer.

Conclusions:

  • Computationally prioritized high-risk FZD8 SNPs have significant structural and functional impacts relevant to tumorigenesis.
  • These identified SNPs can serve as targets for population-based genetic studies and future drug development for FZD8-related cancers.
Keywords:
AGO2FZD8Gene silencingPost-translational modificationUTRmiRNAnsSNP

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