Kinesins, such as KIF4A, are microtubule-based motor proteins that generate directional movement along microtubules. They are involved in many crucial cellular processes, including cell division.
Knowledge on genotype-phenotype correlation is still sparse due to the limited number of patients reported. Most patients are harboring missense variants or splicing variants. Diagnostic testing can be provided by single gene sequencing or via Panel/Exome/Genome-sequencing.
So far the KIF4A variants involve the same functional domains in the group of patients with congenital anomalies and the group with a primarily neurodevelopmental disorder without major anomalies. Variants affecting the kinesin motor domain are only present in patients with congenital anomalies.
KIF4A is predicted to be loss-of-function intolerant with a pLI = 1 in gnomAD, synonymous Z score 0.74, and missense Z score 2.56). The missense variants are all localized within known functional domains including the kinesin motor domain, responsible for ATP hydrolysis and microtubule binding, and the PRC1 binding and coiled coil domain. KIF4A effects a cell-cycle dependent translocation of PRC1, a cytokinesis protein, to the ends of the spindle molecules during mitosis.
KIF4A