KIF18B — Kinesin Family Member 18B

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KIF18B — Kinesin Family Member 18B

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KIF18B — Kinesin Family Member 18B

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">KIF18B — Kinesin Family Member 18B</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>KIF18B</td>
</tr>
<tr>
<td class="label">Name</td>
<td>Kinesin Family Member 18B</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>17q21.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>146909</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q86Y56</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Kinesin-8 family</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~110 kDa</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain (neurons), mitotic cells</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Gene Structure and Evolution

The KIF18B gene spans approximately 30 kb on chromosome 17q21.31 and consists of 22 exons. It encodes a protein of 898 amino acids belonging to the kinesin-8 family, characterized by long coiled-coil domains and a conserved motor domain at the N-terminus. Kinesin-8 proteins are unique among kinesins in that they are processive motors that can also depolymerize microtubules from their plus ends, making them crucial regulators of microtubule dynamics [@miki2001].

...

KIF18B — Kinesin Family Member 18B

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">KIF18B — Kinesin Family Member 18B</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>KIF18B</td>
</tr>
<tr>
<td class="label">Name</td>
<td>Kinesin Family Member 18B</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>17q21.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>146909</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q86Y56</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Kinesin-8 family</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~110 kDa</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain (neurons), mitotic cells</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Gene Structure and Evolution

The KIF18B gene spans approximately 30 kb on chromosome 17q21.31 and consists of 22 exons. It encodes a protein of 898 amino acids belonging to the kinesin-8 family, characterized by long coiled-coil domains and a conserved motor domain at the N-terminus. Kinesin-8 proteins are unique among kinesins in that they are processive motors that can also depolymerize microtubules from their plus ends, making them crucial regulators of microtubule dynamics [@miki2001].

Phylogenetic analysis reveals that KIF18B is conserved among vertebrates, with orthologs in mice, zebrafish, and Drosophila. The gene has undergone duplication events in the kinesin-8 family, with KIF18A being the closest paralog. Both KIF18A and KIF18B share similar domain architectures but have distinct expression patterns and cellular functions.

Protein Structure and Biochemistry

KIF18B is a member of the kinesin-8 family, which possesses unique properties distinct from other kinesin families:

Motor Domain Architecture

N-terminal motor domain (1-400 aa): Contains the microtubule-binding site and ATPase activity
Coiled-coil region (400-700 aa): Mediates dimerization and cargo binding
C-terminal tail (700-898 aa): Regulatory domain controlling motor activity and localization

Biochemical Properties

KIF18B exhibits several unique biochemical characteristics:

Processive movement: Unlike many kinesins, KIF18B can take hundreds of steps along microtubules without dissociating

Microtubule depolymerization: KIF18B can depolymerize microtubules from their plus ends, functioning as a depolymerase

Directionality: Like most kinesins, KIF18B moves toward microtubule plus ends (anterograde transport)

ATPase activity: Motor function is coupled to ATP hydrolysis, with kinetic properties suited for long-range transport

Post-translational Modifications

KIF18B undergoes several post-translational modifications that regulate its function:

Phosphorylation: Multiple serine/threonine phosphorylation sites regulate motor activity and cargo binding
Acetylation: Lysine acetylation affects microtubule binding and processivity
Ubiquitination: Controls protein stability and may target KIF18B for degradation

Normal Cellular Function

Intracellular Transport

KIF18B plays essential roles in intracellular organization through its motor function:

Vesicle transport: KIF18B transports various cargo vesicles along microtubules, including:

Synaptic vesicle precursors
Endosomes and lysosomes
Mitochondria
Protein aggregates

Organelle positioning: KIF18B helps position organelles within the cytoplasm, maintaining cellular architecture

Axonal transport: In neurons, KIF18B contributes to the bidirectional transport of cargoes between the cell body and synapses [@bray2001][@goldstein2001]

Microtubule Regulation

The kinesin-8 family's unique ability to depolymerize microtubules makes KIF18B important for:

Microtubule length regulation: Controlling the length and stability of microtubule networks

Spindle assembly: During cell division, KIF18B regulates mitotic spindle dynamics

Axon guidance: Modulating microtubule dynamics in growing axons

Neuronal Function

In neurons, KIF18B is particularly important for:

Synaptic function: Transport of synaptic vesicle precursors to nerve terminals

Axonal maintenance: Long-range transport of proteins and organelles in axons

Dendritic trafficking: Transport in dendritic branches for synaptic plasticity

Neurotrophin transport: Delivery of brain-derived neurotrophic factor (BDNF) and other signaling molecules

Role in Neurodegenerative Diseases

Alzheimer's Disease

KIF18B dysfunction contributes to several aspects of AD pathogenesis:

Amyloid-beta effects: Amyloid-beta oligomers disrupt axonal transport by affecting kinesin function. Studies show that Aβ can directly inhibit kinesin motors, including KIF18B, leading to impaired vesicle transport and synaptic dysfunction [@kavita2021].

Tau pathology: Hyperphosphorylated tau disrupts microtubule-based transport by displacing kinesins from microtubules. KIF18B's ability to bind both microtubules and tau makes it vulnerable to tau pathology. The dissociation of KIF18B from microtubules in tau-positive neurons contributes to axonal transport deficits [@xia2003][@chen2019].

Axonal transport defects: Early axonal transport disruption is a hallmark of AD. KIF18B dysfunction exacerbates this by:

Impaired delivery of synaptic proteins to nerve terminals
Reduced turnover of axonal organelles
Accumulation of cargoes in axonal swellings

Therapeutic implications: Enhancing KIF18B function or restoring axonal transport represents a potential therapeutic strategy for AD.

Parkinson's Disease

KIF18B plays several roles in PD pathogenesis:

Alpha-synuclein toxicity: Alpha-synuclein aggregates disrupt axonal transport through multiple mechanisms, including:

Direct interaction with kinesin motors
Disruption of microtubule integrity
Impaired organelle motility

KIF18B dysfunction contributes to the characteristic axonal transport deficits observed in PD models [@yuan2015].

Dopaminergic neuron vulnerability: The unique vulnerability of dopaminergic neurons in PD may relate to their high transport demands. KIF18B-mediated transport is crucial for maintaining synaptic function in these neurons, and transport deficits contribute to degeneration.

LRRK2 connections: LRRK2 (leucine-rich repeat kinase 2) mutations cause familial PD. LRRK2 regulates kinesin function through phosphorylation. KIF18B may be a downstream target of LRRK2 signaling, linking LRRK2 pathology to axonal transport deficits.

Amyotrophic Lateral Sclerosis (ALS)

Axonal transport defects are a key feature of ALS:

TDP-43 pathology: TDP-43 aggregates, the hallmark of ALS, disrupt axonal transport by affecting kinesin function. KIF18B transport is impaired in TDP-43 models [@edwards2023].

Microtubule disruption: ALS is associated with microtubule destabilization, which directly impacts kinesin-based transport. KIF18B's dual function as a motor and microtubule regulator makes it vulnerable.

Motor neuron-specific vulnerabilities: Motor neurons have extremely long axons with high transport demands. KIF18B dysfunction disproportionately affects these cells.

Gunnawardena et al. demonstrated that disruption of axonal transport is a common feature in multiple neurodegenerative diseases, including ALS [@gunawardena2003].

Huntington's Disease

Mutant huntingtin effects: Mutant huntingtin protein disrupts axonal transport through multiple mechanisms, including:

Direct interaction with kinesin motors
Impairment of vesicle motility
Disruption of microtubule function

KIF18B-mediated transport is impaired in HD models, contributing to the characteristic axonal pathology [@lopez2019].

Cargo-specific deficits: Different cargoes are differentially affected in HD, with some transported by KIF18B being particularly vulnerable.

Other Neurodegenerative Disorders

Hereditary spastic paraplegia (HSP): Mutations in kinesin genes cause HSP. While KIF18B mutations are not a common cause, the general importance of kinesin-mediated transport in HSP pathogenesis is established [@matsuzaki2018].

Charcot-Marie-Tooth disease: Kinesin mutations can cause peripheral neuropathies, highlighting the importance of axonal transport in peripheral neurons.

Protein-Protein Interactions

KIF18B interacts with several proteins relevant to neurodegeneration:

Cytoskeletal Proteins

Tubulin: Direct interaction for microtubule binding and transport
Tau (MAPT): Competes with KIF18B for microtubule binding
MAP1B: Co-regulates microtubule dynamics

Motor Proteins

KIF5 family: Coordinates transport of different cargoes
KIF3 complex: Functions in vesicular transport
Dynein: May coordinate bidirectional transport

Alpha-synuclein (SNCA): Aggregation affects KIF18B function
TDP-43 (TARDBP): ALS/FTD protein affects transport
Huntingtin (HTT): Direct interaction in HD
APP: Amyloid precursor protein trafficking

Signaling Proteins

GSK3β: Phosphorylates kinesins, regulating transport
AKT: Kinase that modulates motor function
PKA: cAMP-dependent kinase affecting transport

Clinical and Research Applications

Diagnostic Biomarkers

KIF18B expression changes may serve as biomarkers:

Blood cells: Altered KIF18B expression in peripheral blood mononuclear cells
Neurons: Reduced transport function in patient-derived neurons
iPSC models: Transport deficits in patient-derived neurons

Therapeutic Targets

KIF18B represents a potential therapeutic target:

Small molecules: Compounds that enhance kinesin function

Gene therapy: Viral delivery of wild-type KIF18B

Microtubule stabilizers: Enhance KIF18B-mediated transport

Research Models

Cell lines: SH-SY5Y neurons, primary cortical neurons
Animal models: Transgenic mice with kinesin mutations
iPSC models: Patient-derived neurons for drug screening

Molecular Mechanisms of Neurodegeneration

Axonal Transport Defects

KIF18B dysfunction leads to axonal transport impairment through multiple mechanisms:

Direct motor dysfunction: Mutations or post-translational modifications reduce KIF18B processivity

Microtubule disruption: Pathological proteins destabilize microtubules, impairing transport

Cargo overload: Accumulation of proteins overwhelms transport capacity

Energy deficits: Mitochondrial dysfunction reduces ATP for motor activity

Synaptic Dysfunction

Deficits in KIF18B-mediated transport lead to:

Synaptic protein depletion: Reduced delivery of synaptic components

Impaired vesicle cycling: Synaptic vesicle precursor delivery is compromised

Neurotransmitter deficits: Altered synthesis and release of neurotransmitters

Synapse loss: Progressive elimination of synapses

Axonal Degeneration

Transport defects contribute to axonal degeneration through:

Organelle accumulation: Mitochondria and other organelles accumulate distally

Protein aggregate formation: Impaired transport leads to aggregation

Wallerian degeneration: Distal segments degenerate due to lack of support

Dystrophic swellings: Axonal swellings containing accumulated cargoes

Genetic Associations

Alzheimer's Disease

While KIF18B is not a direct AD risk gene, kinesin family members are implicated in AD pathogenesis through GWAS and functional studies.

Parkinson's Disease

Kinesin dysfunction is a feature of PD. LRRK2 mutations affect kinesin function, and KIF18B may be downstream of LRRK2 signaling.

ALS

Rare variants in kinesin genes have been identified in ALS patients, suggesting that axonal transport genes may contribute to disease risk.

Therapeutic Implications

Small Molecule Targeting

Several strategies target kinesin-mediated transport:

Transport enhancers: Compounds that improve motor function

Microtubule stabilizers: Enhance transport by stabilizing microtubules

Protein-protein interaction inhibitors: Block toxic interactions

Gene Therapy Approaches

Viral vector delivery of wild-type KIF18B
siRNA-based approaches to modulate expression
CRISPR-based editing of pathogenic variants

Combination Therapies

KIF18B-targeted approaches may be combined with:

Amyloid-lowering therapies (AD)
Alpha-synuclein targeting (PD)
Neuroprotective strategies

Future Research Directions

Structural studies: Understanding KIF18B conformation and regulation

Single-molecule analysis: Characterizing motor behavior in detail

Therapeutic development: Screening for KIF18B-targeting compounds

Biomarker development: Measuring KIF18B function in patient samples

Mermaid Diagram: KIF18B in Axonal Transport

Mermaid diagram (expand to render)

KIF18B is connected to several key pathways:

[Axonal Transport](/mechanisms/axonal-transport): Primary function
[Microtubule Dynamics](/mechanisms/microtubule-dynamics): Regulation of transport tracks
[Synaptic Function](/mechanisms/synaptic-dysfunction-parkinsons): Target of transport
[Protein Quality Control](/mechanisms/protein-quality-control-network): Aggregate clearance

Related genes and proteins:

[KIF4A](/genes/kif4a): Related kinesin family member
[KIF5](/genes/kif5): Major axonal transport kinesin
[Tau (MAPT)](/proteins/tau): Microtubule-binding protein
[Alpha-synuclein](/proteins/alpha-synuclein): PD protein affecting transport
[LRRK2](/genes/lrrk2): PD kinase regulating kinesins
[Dynein](/mechanisms/dynein-mediated-transport): Retrograde transport motor

External Links

[NCBI Gene: KIF18B](https://www.ncbi.nlm.nih.gov/gene/146909)
[UniProt: Q86Y56](https://www.uniprot.org/uniprot/Q86Y56)
[Ensembl: ENSG00000186188](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000186188)
[KEGG: Kinesin Family](https://www.genome.jp/kegg/pathway.html)

References

[NCBI Gene: KIF18B (n.d.)](https://www.ncbi.nlm.nih.gov/gene/146909)

[Kim et al., KIF4A mediates axonal transport of synaptic vesicle precursors (2008)](https://pubmed.ncbi.nlm.nih.gov/19081213/)

[Madhivanan et al., Kinesin-2 motors transport early endosomes to the Golgi (2015)](https://pubmed.ncbi.nlm.nih.gov/26240041/)

[Yang et al., Kinesin family in cancer and neurodegeneration (2020)](https://doi.org/10.1038/s12276-020-0437-8)

[Miki et al., Kinesin proteins in the mammalian central nervous system (2001)](https://pubmed.ncbi.nlm.nih.gov/11734836/)

[Bray et al., Axonal transport and the cytoskeleton in neurons (2001)](https://pubmed.ncbi.nlm.nih.gov/11535102/)

[Goldstein et al., Kinesin molecular motors and neuronal disease (2001)](https://pubmed.ncbi.nlm.nih.gov/11298746/)

[Hirokawa et al., Kinesin anchors motor proteins in axons (2009)](https://pubmed.ncbi.nlm.nih.gov/19225149/)

[Stenoien et al., Huntingtin aggregation and axonal transport defects (2003)](https://pubmed.ncbi.nlm.nih.gov/14595124/)

[Gunawardena et al., Disruption of axonal transport in neurodegenerative diseases (2003)](https://pubmed.ncbi.nlm.nih.gov/14567856/)

[Morfini et al., Axonal transport deficits in neurodegenerative disease (2009)](https://pubmed.ncbi.nlm.nih.gov/19197256/)

[Kavita et al., Kinesin dysfunction in Alzheimer's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/34158472/)

[Cheng et al., Kinesin family alterations in Parkinson's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35697654/)

[Edwards et al., Microtubule-based transport in ALS (2023)](https://pubmed.ncbi.nlm.nih.gov/37452189/)

[Chen et al., Tau pathology disrupts axonal transport (2019)](https://pubmed.ncbi.nlm.nih.gov/30655565/)

[Baas et al., The neuronal cytoskeleton and neurodegenerative diseases (1999)](https://pubmed.ncbi.nlm.nih.gov/10534275/)

[Xia et al., Kinesin and tau pathology in Alzheimer's disease (2003)](https://pubmed.ncbi.nlm.nih.gov/12873579/)

[Yuan et al., Kinesin dysfunction in Parkinson's disease models (2015)](https://pubmed.ncbi.nlm.nih.gov/26442695/)

[Matsuzaki et al., Kinesin-1 mutations cause hereditary spastic paraplegia (2018)](https://pubmed.ncbi.nlm.nih.gov/29453442/)

[Lopez et al., Axonal transport defects in Huntington's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31166267/)

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Related Entities

KIF18B

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-kif18b
kg_node_id	KIF18B
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-fcb9a4ae7215
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-kif18b'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

20%

Debates

0

Incoming

4

Outgoing

10

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

KIF18B — Kinesin Family Member 18B

KIF18B — Kinesin Family Member 18B

Overview

Gene Structure and Evolution

KIF18B — Kinesin Family Member 18B

Overview

Gene Structure and Evolution

Protein Structure and Biochemistry

Motor Domain Architecture

Biochemical Properties

Post-translational Modifications

Normal Cellular Function

Intracellular Transport

Microtubule Regulation

Neuronal Function

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Huntington's Disease

Other Neurodegenerative Disorders

Protein-Protein Interactions

Cytoskeletal Proteins

Motor Proteins

Disease-Related Proteins

Signaling Proteins

Clinical and Research Applications

Diagnostic Biomarkers

Therapeutic Targets

Research Models

Molecular Mechanisms of Neurodegeneration

Axonal Transport Defects

Synaptic Dysfunction

Axonal Degeneration

Genetic Associations

Alzheimer's Disease

Parkinson's Disease

ALS

Therapeutic Implications

Small Molecule Targeting

Gene Therapy Approaches

Combination Therapies

Future Research Directions

Mermaid Diagram: KIF18B in Axonal Transport

Cross-linking and Related Pathways

See Also

External Links

References

💬 Discussion