Gene Function: 

The KIF1A protein belongs to the kinesin-3 family. Kinesins are a large family of ATP-dependent molecular motors that drive intracellular transport along microtubules, primarily in the plus direction (in the case of KIF1A, toward axon synaptic terminals). All kinesins contain a conserved motor domain, which undergoes cycles of ATP hydrolysis modulating binding and movement along microtubules.

KIF1A is a murine homolog of Caenorhabditis elegans, and undergoes monomer to dimer transition upon cargo binding. It is an important transporter of synaptic vesicle precursors along microtubule bundles to the axon terminal. Homozygous inactivation of KIF1A in mice leads to severe motor and sensory disturbances and the pups die within 24 h of birth. 

Pathologically, a decrease in the density of presynaptic proteins at the nerve terminals, a concomitant decrease in the number of synaptic vesicles at nerve terminals as well as subsequent neuronal degeneration. This severe phenotype caused by complete absence of gene function demonstrates the importance of the KIF1A motor protein in axon maintenance and transport of vesicles in mice. (Nieh et al)

Data on this site was collected by Lia Boyle and presented to KIF1A families on April 14, 2017 at a meeting led by Clinical Geneticist, Wendy Chung, MD, PhD. The presentation took place at Columbia University Medical Center. Available data has changed since April, 2017 as more families make contact and KIF1A becomes recognized as a very relevant rare disease requiring urgent scientific attention. 

KIF1A - Related Disorder is a rare disease caused by a mutation in the KIF1A gene.

  • The first individual with a known KIF1A variant was identified in 2011 Since then, 16 papers have been published describing clinical findings for 66 individuals.

Mutations in KIF1A cause the following disorders:

  • Cognitive impairment
  • Cerebellar atrophy
  • Ataxia
  • Spastic paraplegia
  • Optic nerve atrophy
  • Peripheral neuropathy
  • Epilepsy​​​​