Deep learning-based assessment of missense variants in the <i>COG4</i> gene presented with bilateral congenital cataract.

ABSTRACT:

Objective

We compared the protein structure and pathogenicity of clinically relevant variants of the COG4 gene with AlphaFold2 (AF2), Alpha Missense (AM), and ThermoMPNN for the first time.

Methods and analysis

The sequences of clinically relevant Cog4 missense variants (one novel identified p.Y714F and three pre-existing p.G512R, p.R729W and p.L769R from Uniprot Q9H9E3) were imported into AF2 for protein structural prediction, and the pathogenicity was estimated using AM and ThermoMPNN. Different pathogenicity metrics were aggregated with principal component analysis (PCA) and further analysed at three levels (amino acid position, substitution and post-translation) based on all possible Cog4 missense variants (n=14 915).

Results

Localised protein structural im

SUBMITTER: Xiao B 

PROVIDER: S-EPMC11751923 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature