Distinct Clinical Phenotypes in KIF1A-Associated Neurological Disorders Result from Different Amino Acid Substitutions at the Same Residue in KIF1A.

ABSTRACT: KIF1A is a neuron-specific kinesin motor responsible for intracellular transport along axons. Pathogenic KIF1A mutations cause KIF1A-associated neurological disorders (KAND), a spectrum of severe neurodevelopmental and neurodegenerative conditions. While individual KIF1A mutations have been studied, how different substitutions at the same residue affect motor function and disease progression remains unclear. Here, we systematically examine the molecular and clinical consequences of mutations at three key motor domain residues-R216, R254, and R307-using single-molecule motility assays and genotype-phenotype associations. We find that different substitutions at the same residue produce distinct molecular phenotypes, and that homodimeric mutant motor properties correlate with de

SUBMITTER: Rao L 

PROVIDER: S-EPMC12109325 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature