KIF5A

This gene encodes a member of the kinesin family of proteins. Members of this family are part of a multisubunit complex that functions as a microtubule motor in intracellular organelle transport. Mutations in this gene cause autosomal dominant spastic paraplegia 10.

Full Name

kinesin family member 5A

Function

Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL). Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner. The ZFYVE27-KIF5A complex contributes to the vesicular transport of VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 proteins in neurons. Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation.

Biological Process

Anterograde axonal protein transportISS:UniProtKB
Anterograde dendritic transport of neurotransmitter receptor complexManual Assertion Based On ExperimentIBA:GO_Central
Axon guidanceManual Assertion Based On ExperimentIBA:GO_Central
Chemical synaptic transmissionManual Assertion Based On ExperimentTAS:ProtInc
Cytoskeleton-dependent intracellular transportManual Assertion Based On ExperimentIBA:GO_Central
Microtubule-based movementManual Assertion Based On ExperimentIBA:GO_Central
Retrograde neuronal dense core vesicle transportISS:ARUK-UCL
Synaptic vesicle transportManual Assertion Based On ExperimentIBA:GO_Central
Vesicle-mediated transportISS:UniProtKB

Cellular Location

Cytoplasm, perinuclear region; Cytoplasm, cytoskeleton; Perikaryon. Concentrated in the cell body of the neurons, particularly in the perinuclear region.

Involvement in disease

Spastic paraplegia 10, autosomal dominant (SPG10):
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
Myoclonus, intractable, neonatal (NEIMY):
An autosomal dominant neurologic disorder characterized by severe, infantile-onset myoclonic seizures, hypotonia, optic nerve abnormalities, dysphagia, apnea, and early developmental arrest. Brain imaging shows a progressive leukoencephalopathy. Some patients may die in infancy.
Amyotrophic lateral sclerosis 25 (ALS25):
A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS25 is an autosomal dominant form with variable adult onset and incomplete penetrance.