Bioinformatics analysis of de novo missense variants in Kinesin Family Member 1A (KIF1A) in autism spectrum disorder: a case report and literature review

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder influenced by both rare and common genetic variants. Among the genes implicated, Kinesin Family Member 1A (KIF1A), which encodes a neuronal kinesin motor protein, has emerged as a potential contributor to ASD pathogenesis. In this case report and literature review, we describe a comorbidity-free ASD proband carrying a novel de novo KIF1A missense variant (c.A664C, p.N222H) and evaluate its pathogenic potential through comprehensive bioinformatics analyses. Whole-exome sequencing (WES) and Sanger sequencing were performed in a family trio, and gene expression profiling was conducted using the Human Brain Transcriptome (HBT) database to examine spatiotemporal KIF1A expression during neurodevelopment. The structural and functional impact of four KIF1A variants, including the novel one, was analyzed using PredictProtein, SWISS-MODEL, and PyMOL. KIF1A was found to be highly expressed during embryonic brain development and to stabilize postnatally, indicating an essential role in neuronal maturation. Structural modeling demonstrated that all four variants disrupted the secondary and tertiary conformations of the KIF1A protein, altering key hydrogen-bonding patterns and potentially impairing adenosine triphosphatase (ATPase)-driven vesicular transport along microtubules. The absence of comorbidities in the proband further supports a direct association between KIF1A dysfunction and ASD-related behavioral phenotypes. Although functional validation could not be performed, these bioinformatics findings highlight KIF1A as a plausible ASD risk gene and underscore the importance of integrating rare variant analysis with polygenic context in understanding ASD genetics.