KIF1A
Function
Motor for anterograde axonal transport of synaptic vesicle precursors (PubMed:33880452). Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons. The interaction calcium-dependent with CALM1 increases vesicle motility and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites.
Involvement in disease
Spastic paraplegia 30A, autosomal dominant
SPG30A
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. Some SPG30A patients have a pure form of the disorder, limited to spastic paraplegia, whereas others may have a complicated form that includes additional features such as cognitive dysfunction, learning disabilities, peripheral sensorimotor neuropathy, urinary sphincter problems, and/or cerebellar atrophy. SPG30A is characterized by onset in the first or second decades of unsteady spastic gait and hyperreflexia of the lower limbs. Inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Spastic paraplegia 30B, autosomal recessive
SPG30B
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. Some SPG30B patients have a pure form of the disorder, limited to spastic paraplegia, whereas others may have a complicated form that includes additional features such as cognitive dysfunction, learning disabilities, peripheral sensorimotor neuropathy, urinary sphincter problems, and/or cerebellar atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Neuropathy, hereditary sensory, 2C
HSN2C
A neurodegenerative disorder characterized by onset in the first decade of progressive distal sensory loss leading to ulceration and amputation of the fingers and toes. Affected individuals also develop distal muscle weakness, primarily affecting the lower limbs.
None
The disease is caused by variants affecting the gene represented in this entry.
NESCAV syndrome
NESCAVS
An autosomal dominant neurodegenerative disorder with variable manifestations. Main features are delayed psychomotor development, progressive spasticity, intellectual disability, speech delay, and learning disabilities. Some patients never achieve ambulation. Additional variable features are cortical visual impairment, often associated with optic atrophy, axonal peripheral neuropathy, seizures, dysautonomia, ataxia, and dystonia. Brain imaging often shows progressive cerebellar atrophy and thin corpus callosum. Disease onset is in infancy or early childhood.
None
The disease is caused by variants affecting the gene represented in this entry.
KIF1A dysfunction is associated with a large spectrum of neurologic disorders, including HSN2C, SPG30 and NESCAVS. It has been proposed to collectively name them KIF1A-Associated Neurological Disorder (KAND). Some variants reported here are based on this broad classification.
Sequence Similarities
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Unc-104 subfamily.
Tissue Specificity
Expressed in neurons.
Cellular localization
- Cytoplasm
- Cytoskeleton
- Cell projection
- Neuron projection
- Cell projection
- Axon
- Cytoplasm
- Perinuclear region
- Synapse
- Cytoplasmic vesicle
- Secretory vesicle
- Neuronal dense core vesicle membrane
- Peripheral membrane protein
- Cytoplasmic side
- Within neuronal cells concentrated in the axon, with smaller amounts in the perinuclear and synaptic regions (By similarity). Accumulates at the distal tip of growing neurites.
Alternative names
ATSV, C2orf20, KIF1A, Kinesin-like protein KIF1A, Axonal transporter of synaptic vesicles, Microtubule-based motor KIF1A, Unc-104- and KIF1A-related protein, hUnc-104