KIF5A is located on 12q13.3 and codes for KIF5A, belonging to the kinesin-1 family, which makes up the heavy chain of microtubule-based motor proteins. It consists of 3 domains i.e. an N-terminal globular domain, a long alpha-helical coiled coil domain, and a small C-terminal globular domain.
The kinesin heavy chain (KHC) proteins are part of a multisubunit complex (kinesin-I) that acts as a plus-end–directed microtubule motor involved in anterograde transport of membranous organelles in nerve axons
Variants in the N-terminal motor domain of KIF5A, affecting its motor domain, are chiefly linked to two neurodegenerative diseases i.e. hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). On the other hand, variants in the C-terminal region may affect its cargo-binding region, and have been linked to ALS (Faruq M et al, 2019). According to Nicolas et al, 2018, variants in KIF5A cause disease by hindering axonal transport, resulting in accumulation of cytoplasmic protein aggregates at the neuronal cell body and a deficiency of cargo proteins at neurite terminals.
KIF5A