Structural and Pathogenic Impacts of ABCA4 Variants in Retinal Degenerations-An In-Silico Study.
Int J Mol Sci
; 24(8)2023 Apr 14.
Article
en En
| MEDLINE
| ID: mdl-37108442
ABSTRACT
The retina-specific ATP-binding cassette transporter protein ABCA4 is responsible for properly continuing the visual cycle by removing toxic retinoid byproducts of phototransduction. Functional impairment caused by ABCA4 sequence variations is the leading cause of autosomal recessive inherited retinal disorders, including Stargardt disease, retinitis pigmentosa, and cone-rod dystrophy. To date, more than 3000 ABCA4 genetic variants have been identified, approximately 40 percent of which have not been able to be classified for pathogenicity assessments. This study examined 30 missense ABCA4 variants using AlphaFold2 protein modeling and computational structure analysis for pathogenicity prediction. All variants classified as pathogenic (n = 10) were found to have deleterious structural consequences. Eight of the ten benign variants were structurally neutral, while the remaining two resulted in mild structural changes. This study's results provided multiple lines of computational pathogenicity evidence for eight ABCA4 variants of uncertain clinical significance. Overall, in silico analyses of ABCA4 can provide a valuable tool for understanding the molecular mechanisms of retinal degeneration and their pathogenic impact.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Degeneración Retiniana
/
Retinitis Pigmentosa
/
Distrofias de Conos y Bastones
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos