In-silico Identification and Structural Characterization of a Novel Missense Variant (p.Ala2Thr) in the MCPH1 Associated with Autosomal Recessive Primary Microcephaly

Abstract

Autosomal recessive primary microcephaly is a genetically diverse neurodevelopmental disorder marked by reduced brain size. This study used an integrative bioinformatics approach to identify pathogenic variants in the MCPH1 gene. Data from GeneCards and DisGeNET highlighted MCPH1 as a key candidate. A missense variant (p.Ala2Thr) was identified using gnomAD and validated via UniProt. Functional analysis showed MCPH1 involvement in cell cycle regulation and DNA damage response. In silico tools (PolyPhen-2 and SIFT) predicted the variant as deleterious. Structural and docking analyses suggested that the mutation may alter protein stability and interaction dynamics, potentially affecting its function.