KIF5C encodes Kinesin heavy chain isoform 5C, a member of the Kinesin-1 family of microtubule-based motor proteins. The KIF5C heavy chain N-terminal motor globule subunit associates with another N-terminal heavy chain and two C-terminal light chains to form the complete functioning kinesin tetramer. Kinesins are involved in transporting organelles in eukaryotic cells; KIF5C in particular is involved in transporting granules containing RNA as well as RNA-specific and translation specific proteins bi-directionally on dendrites.
Defective KIF5C is associated with Cortical Dysplasia, Complex, with other Brain Malformations 2 (CDCBM2), a congenital disorder of the nervous system caused by disrupted axonal guidance and uncontrolled neuronal migration.
KIF5C is located on the q arm of chromosome 2 and is 151,547 bases long ranging from 148,875,223 to 149,026,759 base pairs pter. It contains 26 exons and translates into a 957aa long protein with a molecular weight of 109,495 Da. KIF5C is expressed most abundantly in the brain as well as the prostrate and testis; it is also moderately expressed in other tissues such as the kidney and small intestine. 1 additional isoform as well as 15 paralog genes exist. KIF5C is thought to function in axon guidance, mRNA transport, and protein localization through cytoskeleton dependent intracellular transport.
Heterozygous missense mutations in KIF5C have been associated with cortical dysplasia, complex, with other brain malformations 2 (CDCBM2). Functional studies of the reported mutations revealed impaired ATP hydrolysis and the resulting loss of protein motor function.
Al-Shamsi et al., 2016 performed Whole Exome Sequencing in 85 Emirati patients who were admitted to the metabolic unit with un-diagnosable inborn errors of metabolism and other genetic disorders. Among the cohort in whom variants of uncertain significance were likely pathogenic, 1 patient was diagnosed with Cortical Dysplasia, Complex with other brain malformations 2 (CDCBM2). A previously reported de novo heterozygous missense transition in KIF5C (c.404A>G, p.Tyr289Cys) was identified as the probable cause. A non-pathogenic heterozygous transition in NRXN1 (c.1835A>G, p.Asp612Gly) was additionally identified in the parents and one sibling.