Structure-function analysis of CNGA3-associated achromatopsia patient variants complements clinical genomics in pathogenicity determination.

ABSTRACT:

Background

Achromatopsia is an autosomal recessive genetic disease, and 95% of achromatopsia patients carry pathogenic mutations in the CNGA3 and CNGB3 genes. Once translated, these genes function together by forming a cone photoreceptor CNG channel protein complex.

Results

There are 150 CNGA3 missense variants reported in achromatopsia patients, but the pathogenicity of 103 variants remains unknown due to inconclusive genetic information. Here, we present clinical features of a novel CNGA3 variant in an achromatopsia patient and demonstrate its pathogenicity by a three-dimensional (3D) proteoform-based structure-function analysis. We first identified six proteotypic groups using 47 pathogenic missense variants with distinctive functional consequences by mapping their spatia

SUBMITTER: Rasmussen DK 

PROVIDER: S-EPMC12125802 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature