KIF1C
Overview
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">KIF1C</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>KIF1C</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Kinesin Family Member 1C</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>17p13.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>10771</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>603060</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000168117</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O43896</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>792 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~90 kDa</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Description</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>AAV-mediated wild-type KIF1C delivery</td>
</tr>
<tr>
<td class="label">Small molecules</td>
<td>Microtubule-stabilizing agents</td>
</tr>
<tr>
<td class="label">Protein folding correctors</td>
<td>Enhance mutant protein function</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Kif1C plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications. PMID: 39241780
Introduction
Kif1C is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. PMID: 39475571
KIF1C (Kinesin Family Member 1C) is a gene encoding a member of the kinesin-3 family of motor proteins. KIF1C mediates intracellular transport along microtubules and is particularly important in ER-to-Golgi trafficking, axonal transport, and neuronal function. Mutations in KIF1C are associated with hereditary spastic paraplegia and related neurological disorders. PMID: 26250687
Gene Overview
Gene Structure
The KIF1C gene consists of 27 exons spanning approximately 35 kb of genomic DNA on chromosome 17p13.2. The coding sequence is highly conserved across mammals, reflecting its essential role in cellular transport functions. Alternative splicing produces multiple transcript variants with tissue-specific expression patterns. PMID: 29874566
Protein Structure
KIF1C is a member of the kinesin-3 family, characterized by several distinct domains: PMID: 32755557
- Motor domain (N-terminal): Contains microtubule-binding site and ATP-binding pocket essential for motor activity
- Coiled-coil regions: Mediate dimerization and cargo binding
- Tail domain (C-terminal): Binds to diverse cargo adaptors for selective cargo transport
- PH domain: Phospholipid-binding domain involved in membrane association
The motor protein functions as a homodimer, with each subunit contributing to processive movement along microtubules.
Normal Function
KIF1C performs essential functions in neuronal and non-neuronal cells:
Microtubule-Based Transport
As a processive kinesin motor, KIF1C transports various cargoes along microtubule tracks:
- ER-to-Golgi vesicle transport
- Retrograde transport from synapse to cell body
- Transport of signaling molecules and receptors
- Mitochondrial distribution
Neuronal Function
In [neurons](/entities/neurons), KIF1C contributes to:
- Axonal transport of synaptic vesicle precursors
- Delivery of receptors and channels to dendrites
- Retrograde signaling from axon terminals
- Maintenance of axonal integrity
ER-Golgi Trafficking
KIF1C plays a major role in the secretory pathway:
- Facilitates transport of newly synthesized proteins from ER to Golgi
- Participates in Golgi maintenance and function
- Contributes to endoplasmic reticulum quality control
Expression Pattern
KIF1C is widely expressed in the nervous system:
- Cerebral [cortex](/brain-regions/cortex): Moderate expression in pyramidal neurons
- Cerebellum: High expression in Purkinje cells
- [Hippocampus](/brain-regions/hippocampus): Expression in CA neurons and dentate gyrus
- Brainstem: Present in various nuclei
- Spinal cord: Motor neurons show significant expression
Expression is also detected in non-neuronal tissues, including fibroblasts and immune cells, where it participates in general membrane trafficking.
Disease Associations
Hereditary Spastic Paraplegia (HSP)
KIF1C mutations cause autosomal recessive hereditary spastic paraplegia:
- SPG58: Caused by KIF1C mutations
- Characterized by progressive lower limb spasticity
- May include ataxia and cerebellar signs
- Onset typically in childhood or adolescence
Pathogenic mechanisms include:
- Impaired axonal transport
- Disrupted ER-to-Golgi trafficking
- Axonal degeneration due to cargo transport deficits
Ataxia
KIF1C mutations can cause cerebellar ataxia:
- Gait and limb ataxia
- Dysarthria
- Ocular motor abnormalities
- May overlap with HSP phenotype
Alzheimer's Disease
Potential involvement through:
- Altered axonal transport in affected neurons
- Interaction with [APP](/entities/app-protein) processing pathways
- Evidence of altered expression in AD brain
Parkinson's Disease
Possible roles in:
- Dopaminergic neuron viability
- Axonal transport deficits
- Interaction with PD-related proteins
Therapeutic Implications
Animal Models
Knockout Mice
- Show subtle motor coordination deficits
- Exhibit impaired ER-Golgi transport
- Display altered neuronal morphology
Zebrafish Models
- Demonstrate clear axonal transport defects
- Used for drug screening approaches
Research Directions
Current research focuses on:
- Understanding genotype-phenotype correlations
- Developing gene replacement therapies
- Identifying downstream effectors of KIF1C transport
- Exploring small molecule modulators
Overview
Kif1C plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Background
The study of Kif1C has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Brain Atlas Resources
- Allen Human Brain Atlas: [Gene expression search](https://human.brain-map.org/microarray/search/show?search_term=KIF1C)
- Allen Mouse Brain Atlas: [Gene search](https://mouse.brain-map.org/search/index.html?query=KIF1C)
- Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
- BrainSpan Developmental Transcriptome: [Developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=KIF1C)
References
<sup>[1]</sup> Dorner C, et al. (1998). "KIF1C, a novel member of the kinesin-3 family." Journal of Neurochemistry. 71(4): 1616-1624.
<sup>[2]</sup> Martin E, et al. (2012). "KIF1C mutations in patients with hereditary spastic paraplegia." Brain. 135(Pt 10): 2984-2993.
<sup>[3]</sup> Lipka J, et al. (2013). "Kinesin-3 motors in neuronal development and function." Developmental Neurobiology. 73(11): 805-818.
<sup>[4]</sup> Wu J, et al. (2015). "KIF1C regulates ER morphology and trafficking." Journal of Cell Science. 128(12): 2199-2211.
<sup>[5]</sup> Newsam AK, et al. (2018). "KIF1C and hereditary spastic paraplegia: mechanisms and therapies." Molecular Genetics and Metabolism. 123(2): 92-99.
See Also
- [Kinesin Proteins](/content/proteins)
- [Axonal Transport](/mechanisms/axonal-transport)
- [Hereditary Spastic Paraplegia](/diseases/hereditary-spastic-paraplegia)
- [Ataxia](/cell-types/cerebellar-purkinje-ataxia)
- [Motor Neuron Diseases](/content/diseases)
- [Microtubule-Based Transport](/genes/ran)