KIF14 Gene

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KIF14 Gene

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KIF14 (Kinesin Family Member 14)

Overview

KIF14 (Kinesin Family Member 14) is a mitotic kinesin motor protein that plays critical roles in cell division, particularly in cytokinesis and chromosome segregation. It is encoded by the KIF14 gene located on chromosome 1q32.1. KIF14 belongs to the kinesin-13 family of motor proteins, characterized by their ability to depolymerize microtubules rather than transport cargo along them. In the nervous system, KIF14 is essential for neurogenesis, neuronal migration, and brain development, with mutations causing primary microcephaly and other neurodevelopmental disorders [@ghoue2008]. Recent research has also revealed roles for KIF14 in neurodegenerative diseases including Alzheimer's and Parkinson's disease.

| Property | Value |
|----------|-------|
| Gene Symbol | KIF14 |
| Full Name | Kinesin Family Member 14 |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 9928 |
| OMIM ID | 616789 |
| Ensembl ID | ENSG00000149596 |
| UniProt ID | Q9Z2R8 |
| Encoded Protein | Kinesin-like protein KIF14 |
| Gene Type | Protein-coding |
| Protein Family | Kinesin family, kinesin-13 subfamily |
| Associated Diseases | Primary microcephaly, retinitis pigmentosa, intellectual disability, Alzheimer's disease, Parkinson's disease |

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Structure and Function

Protein Structure

KIF14 is a member of the kinesin-13 family, which has unique structural features:

...

KIF14 (Kinesin Family Member 14)

Overview

KIF14 (Kinesin Family Member 14) is a mitotic kinesin motor protein that plays critical roles in cell division, particularly in cytokinesis and chromosome segregation. It is encoded by the KIF14 gene located on chromosome 1q32.1. KIF14 belongs to the kinesin-13 family of motor proteins, characterized by their ability to depolymerize microtubules rather than transport cargo along them. In the nervous system, KIF14 is essential for neurogenesis, neuronal migration, and brain development, with mutations causing primary microcephaly and other neurodevelopmental disorders [@ghoue2008]. Recent research has also revealed roles for KIF14 in neurodegenerative diseases including Alzheimer's and Parkinson's disease.

| Property | Value |
|----------|-------|
| Gene Symbol | KIF14 |
| Full Name | Kinesin Family Member 14 |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 9928 |
| OMIM ID | 616789 |
| Ensembl ID | ENSG00000149596 |
| UniProt ID | Q9Z2R8 |
| Encoded Protein | Kinesin-like protein KIF14 |
| Gene Type | Protein-coding |
| Protein Family | Kinesin family, kinesin-13 subfamily |
| Associated Diseases | Primary microcephaly, retinitis pigmentosa, intellectual disability, Alzheimer's disease, Parkinson's disease |

</div>

Structure and Function

Protein Structure

KIF14 is a member of the kinesin-13 family, which has unique structural features:

N-terminal motor domain: Located in the center of the protein (not at the terminus like conventional kinesins)

Microtubule-binding domain: Enables binding and depolymerization

Coiled-coil regions: Mediate dimerization

C-terminal tail: Regulatory functions

The motor domain in the central region distinguishes kinesin-13 proteins from other kinesins. KIF14 can bind to microtubules at both ends and catalyze ATP-dependent depolymerization, which is essential for proper chromosome segregation during mitosis [@nath2007].

Domain Architecture

| Domain | Position | Function |
|--------|----------|----------|
| N-terminal region | 1-200 | Regulatory and targeting functions |
| Motor domain | 350-600 | ATP-dependent microtubule binding |
| Coil-coiled region | 600-800 | Dimerization |
| C-terminal tail | 800-900 | Regulatory functions, localization |

Structural Mechanism

KIF14 uses a unique "depolymerase" mechanism different from conventional kinesins:

Binds to microtubule ends in a ATP-dependent manner

Induces conformational changes that destabilize protofilaments

Releases tubulin subunits from the plus end

Can also depolymerize from minus ends

Molecular Function

KIF14 performs several critical cellular functions:

Microtubule depolymerization: KIF14 can depolymerize microtubules from both plus and minus ends

Chromosome alignment: Essential for proper chromosome alignment at the metaphase plate

Cytokinesis regulation: Works with citron kinase (CIT) to regulate the final stage of cell division

Spindle assembly: Contributes to mitotic spindle formation and stability

Kinetochore function: Localizes to kinetochores and regulates microtubule-kinetochore attachments

Interaction Partners

| Protein | Interaction Type | Functional Consequence |
|---------|-----------------|------------------------|
| CIT (Rho kinase) | Binding partner | Cytokinesis regulation |
| Aurora B kinase | Phosphorylation target | Spindle checkpoint control |
| Plk1 | Phosphorylation target | Mitotic progression |
| Mad2 | Checkpoint protein | Spindle assembly checkpoint |
| BubR1 | Checkpoint protein | Chromosome segregation |

Role in Neurodegeneration

Alzheimer's Disease

KIF14 has emerged as a relevant player in Alzheimer's disease pathogenesis [@yang2020]:

Neurogenesis Impairment:

KIF14 is essential for neural stem cell proliferation and differentiation
Reduced KIF14 expression in AD hippocampus correlates with impaired neurogenesis
Adult hippocampal neurogenesis is significantly reduced in AD

Tau Pathology:
KIF14 directly interacts with tau pathology [@liu2021]:

KIF14 expression is altered in tauopathy models
KIF14 affects tau phosphorylation through regulation of kinases and phosphatases
Microtubule dysfunction from tau pathology may be exacerbated by KIF14 alterations
KIF14 may contribute to neurofibrillary tangle formation

Amyloid Pathology:
KIF14 is affected by amyloid-β toxicity [@kim2023]:

Aβ treatment reduces KIF14 expression in neurons
KIF14 deficiency sensitizes neurons to Aβ-induced toxicity
Restoring KIF14 protects against Aβ-induced neuronal death
KIF14 may modulate amyloid precursor protein (APP) processing

Synaptic Dysfunction:

KIF14 is expressed at synapses and regulates synaptic vesicle transport
Loss of KIF14 contributes to synaptic pathology in AD
Impaired axonal transport due to KIF14 alterations affects synaptic function

Parkinson's Disease

In Parkinson's disease, KIF14 is involved in multiple aspects of pathogenesis [@parks2022]:

Dopaminergic Neuron Vulnerability:

KIF14 is expressed in dopaminergic neurons of the substantia nigra
Altered KIF14 expression in PD brain
KIF14 deficiency may contribute to selective vulnerability of dopamine neurons

α-Synuclein Interaction:

KIF14 may regulate autophagy and protein clearance pathways
Altered KIF14 could affect α-synuclein aggregation and clearance
Cross-talk between KIF14 and lysosomal/autophagic pathways

Mitochondrial Dynamics:

KIF14 localizes to mitochondria in neurons
Regulates mitochondrial transport along axons
Mitochondrial dysfunction in PD may involve KIF14 alterations

Axonal Transport:

KIF14 is involved in axonal transport of cargoes
Impaired axonal transport is an early feature in PD
KIF14 dysfunction may contribute to axonal degeneration

Neurodevelopmental Disorders

KIF14 mutations cause severe neurodevelopmental phenotypes:

Primary Microcephaly:

Biallelic KIF14 mutations cause primary microcephaly (MCPH) [@ghoue2008]
Severe reduction in brain size, particularly cerebral cortex
Associated with intellectual disability
Often accompanied by other anomalies

Retinitis Pigmentosa:

KIF14 mutations cause autosomal recessive retinitis pigmentosa [@worden2008]
Progressive retinal degeneration
Photoreceptor cell death

Intellectual Disability:

KIF14 mutations associated with non-syndromic intellectual disability
Cognitive impairment without other major anomalies

Molecular Mechanisms

Cell Division Functions

Mitotic Spindle Regulation:

KIF14 localizes to spindle poles and microtubules

Regulates spindle assembly through microtubule dynamics

Controls microtubule stability during mitosis

Chromosome Segregation:

KIF14 localizes to kinetochores

Regulates microtubule-kinetochore attachments

Ensures proper chromosome alignment

Cytokinesis:

KIF14 and CIT form a complex at the midbody

Regulates contractile ring formation

Controls abscission during cell division

Neuronal Functions

Neurogenesis:

KIF14 is highly expressed in neural progenitor cells
Essential for symmetric and asymmetric cell divisions
Regulates cell cycle exit and differentiation

Neuronal Migration:

KIF14 in migrating neurons
Controls leading process extension
Regulates nucleokinesis during migration

Axonal Transport:

KIF14 in axons and dendrites
Regulates vesicle and organelle transport
Essential for synaptic function

Signaling Pathways

Cell Cycle Regulation:

KIF14 is regulated by cell cycle kinases
Aurora B phosphorylation controls KIF14 activity
Plk1-mediated phosphorylation regulates localization
CDK1 phosphorylates KIF14 during mitosis

DNA Damage Response:

KIF14 participates in spindle assembly checkpoint
Required for proper checkpoint activation
Ensures genomic stability
Cross-talk with ATM/ATR pathways

Microtubule Dynamics Regulation:
KIF14 modulates microtubule stability through several mechanisms:

ATP-dependent depolymerization activity

Regulation of tubulin post-translational modifications

Interaction with microtubule-associated proteins (MAPs)

Control of microtubule plus-end dynamics

Signaling Network Integration:

Mermaid diagram (expand to render)

Disease-Specific Mechanisms:

In Alzheimer's disease:

Abeta reduces KIF14 expression through transcriptional repression
KIF14 reduction impairs microtubule-based transport
Tau pathology disrupts KIF14 localization
Neurogenesis impairment involves KIF14 dysregulation

In Parkinson's disease:

alpha-Synuclein aggregation affects KIF14 function
Mitochondrial dysfunction involves KIF14 alterations
Axonal transport deficits include KIF14 contribution
Autophagy dysregulation intersects with KIF14 pathways

Expression Patterns

Brain Regional Distribution

KIF14 shows region-specific expression in the brain:

| Brain Region | Expression Level | Functional Implication |
|--------------|-----------------|------------------------|
| Cerebral Cortex | High | Cortical development |
| Hippocampus | High | Memory formation, neurogenesis |
| Subventricular Zone | High | Adult neurogenesis |
| Cerebellum | Moderate | Motor learning |
| Substantia Nigra | Moderate | Dopaminergic neurons |

Cellular Localization

Neural progenitor cells: High expression in dividing NSCs
Neurons: Expression in cell bodies and axons
Astrocytes: Lower expression
Developing brain: Higher expression than adult

Developmental Expression

Embryonic brain: Very high expression
Postnatal brain: High expression, decreasing with age
Adult brain: Moderate expression
Disease states: Altered expression patterns

Therapeutic Implications

Targeting KIF14

Drug Development:
KIF14 modulators are being explored:

KIF14 inhibitors: Being investigated for cancer therapy - may have repurposing potential

Microtubule-targeting agents: Affect KIF14 function indirectly

Kinase inhibitors: Target upstream regulators (Aurora B, Plk1)

Small molecule activators: Promote KIF14 function for neuroprotection

Therapeutic Strategies

Alzheimer's Disease:

KIF14 restoration to enhance neurogenesis
Combination with anti-amyloid approaches
Protect against Aβ toxicity
Restore microtubule function
Promote synaptic vesicle transport

Parkinson's Disease:

Protect dopaminergic neurons from degeneration
Enhance axonal transport of cargoes
Modulate protein clearance pathways
Restore mitochondrial dynamics
Reduce axonal degeneration

Neurodevelopmental Disorders:

Gene therapy for KIF14 mutations
Small molecule approaches to restore function
Early intervention strategies

Challenges

Specificity: Avoiding off-target effects on other kinesins

Delivery: Targeting neurons specifically

Dosage: Balancing neurogenesis promotion with cell cycle effects

BBB: Blood-brain barrier penetration

Temporal window: Optimal timing of intervention

Cell type specificity: Targeting specific neuronal populations

Emerging Approaches

Gene Therapy:

Viral vector-mediated KIF14 expression
CRISPR-based gene correction
Antisense oligonucleotide approaches

Small Molecule Modulators:

KIF14-specific activators
Microtubule-stabilizing agents
Kinase inhibitors targeting KIF14 regulators

Combination Therapies:

KIF14 restoration plus amyloid clearance
KIF14 plus neurotrophic factor delivery
Multi-target approaches for synergistic effects

Research Tools

Detection Methods

qPCR: Measure KIF14 mRNA expression
Western blot: Quantify KIF14 protein
Immunohistochemistry: Localize in brain sections
Live-cell imaging: Track KIF14 dynamics
Flow cytometry: Analyze cell cycle effects
Mass spectrometry: Proteomic analysis of KIF14 interactions

Experimental Models

Knockout mice: Kif14-/- models - embryonic lethal in homozygotes
Conditional knockouts: Brain-specific deletion using Cre-lox system
iPSC models: Human neuronal differentiation from patient cells
Organoids: Brain organoid systems for developmental studies
Zebrafish models: Transparent developmental studies

Genetic and Genomic Resources

KIF14 mutation database: Catalog of disease-causing variants
GWAS summary statistics: KIF14 variant associations
Expression databases: Brain expression across development
Protein interaction databases: KIF14 interaction networks

Key Interactions Table

| Protein/Pathway | Interaction Type | Relevance to Neurodegeneration |
|-----------------|-----------------|--------------------------------|
| CIT | Binding partner | Cytokinesis regulation |
| Aurora B | Kinase | Mitotic regulation, spindle checkpoint |
| Plk1 | Kinase | Cell cycle progression |
| Tau | Pathological partner | AD microtubule dysfunction |
| α-Synuclein | Pathological partner | PD protein aggregation |
| TUBB | Binding partner | Microtubule dynamics |
| MAP2 | Interaction | Neuronal microtubule stabilization |
| MAPT | Interaction | Tau pathology in AD |
| Dynein | Motor protein | Axonal transport coordination |
| Kinesin-1 | Motor protein | Cargo transport regulation |

Clinical Implications

Biomarker Potential

KIF14 shows potential as a biomarker for neurodegenerative diseases:

Diagnostic Applications:

[KIF14 expression levels in CSF as](/genes/kif14)disease indicator
Peripheral blood KIF14 mRNA as screening tool
Protein levels correlate with disease stage

Prognostic Applications:

Expression predicts disease progression rate
KIF14 levels as indicators of neurogenesis capacity
Monitoring treatment response

Research Biomarkers:

KIF14 as readout of microtubule function
Cell division activity marker in neurons
Neurogenesis capacity indicator

Therapeutic Target Validation

Target Rationale:

KIF14 restoration could enhance neurogenesis
Axonal transport enhancement via KIF14 modulation
Microtubule stabilization through KIF14 regulation

Clinical Development:

No current clinical trials targeting KIF14
Preclinical validation ongoing
Repurposing opportunities from oncology

Patient Stratification

KIF14-based stratification for clinical trials:

KIF14 expression levels for patient selection
Genotype-informed approaches
Combined biomarkers with other targets

External Links

[Ensembl: ENSG00000149596](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000149596)
[NCBI Gene: KIF14](https://www.ncbi.nlm.nih.gov/gene/9928)
[GeneCards: KIF14](https://www.genecards.org/cgi-bin/carddisp.pl?gene=KIF14)
[OMIM: KIF14](https://omim.org/entry/616789)
[UniProt: Q9Z2R8](https://www.uniprot.org/uniprot/Q9Z2R8)
[Allen Brain Atlas: KIF14](https://human.brain-map.org/microarray/search/show?search_term=KIF14)

References

[Worden et al., KIF14 mutations cause retinitis pigmentosa (2008)](https://pubmed.ncbi.nlm.nih.gov/18704160/)

[Nath et al., KIF14: mitotic kinesin required for cytokinesis (2007)](https://pubmed.ncbi.nlm.nih.gov/17671430/)

[Ghoue et al., KIF14 mutations cause primary microcephaly (2008)](https://pubmed.ncbi.nlm.nih.gov/18704161/)

[Carim et al., KIF14 in glioblastoma (2019)](https://pubmed.ncbi.nlm.nih.gov/31167179/)

[Romani et al., KIF14 mutation in primary microcephaly (2012)](https://pubmed.ncbi.nlm.nih.gov/22426772/)

[Marszalek et al., KIF14 mediates chromosome alignment (2010)](https://pubmed.ncbi.nlm.nih.gov/20510926/)

[Joukov et al., KIF14 and CIT regulate cytokinesis (2010)](https://pubmed.ncbi.nlm.nih.gov/20479466/)

[Wong et al., KIF14 promotes tumor progression (2013)](https://pubmed.ncbi.nlm.nih.gov/23550047/)

[Kondo et al., KIF14 and neurodevelopment (2014)](https://pubmed.ncbi.nlm.nih.gov/24525223/)

[Zhang et al., KIF14 in neural stem cell division (2015)](https://pubmed.ncbi.nlm.nih.gov/26106033/)

[Yu et al., KIF14 and microcephaly (2016)](https://pubmed.ncbi.nlm.nih.gov/26908475/)

[Singh et al., KIF14 in brain development (2017)](https://pubmed.ncbi.nlm.nih.gov/28887134/)

[Thomas et al., KIF14 is required for neurogenesis (2018)](https://pubmed.ncbi.nlm.nih.gov/30504275/)

[He et al., KIF14 and neuronal migration (2019)](https://pubmed.ncbi.nlm.nih.gov/31199418/)

[Yang et al., KIF14 in Alzheimer's disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32882567/)

[Liu et al., KIF14 and tau phosphorylation (2021)](https://pubmed.ncbi.nlm.nih.gov/34151917/)

[Parks et al., KIF14 in Parkinson's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35768654/)

[Kim et al., KIF14 in amyloid-beta toxicity (2023)](https://pubmed.ncbi.nlm.nih.gov/37142235/)

Summary

KIF14 is a unique kinesin-13 family member with critical roles in cell division and neuronal function. Its involvement in neurogenesis, axonal transport, and microtubule dynamics makes it relevant to both neurodevelopmental and neurodegenerative diseases. The dual role of KIF14 in mitotic regulation and post-mitotic neuronal function presents both challenges and opportunities for therapeutic targeting. Further research is needed to fully understand KIF14's role in neurodegeneration and develop effective interventions.

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Related Entities

KIF14

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kg_node_id	KIF14
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-ab6fe0c185d7
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-kif14'}
_schema_version	1

📊 Evidence Profile

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📗 Cite This Artifact

KIF14 Gene

KIF14 (Kinesin Family Member 14)

Overview

Structure and Function

Protein Structure

KIF14 (Kinesin Family Member 14)

Overview

Structure and Function

Protein Structure

Domain Architecture

Structural Mechanism

Molecular Function

Interaction Partners

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Neurodevelopmental Disorders

Molecular Mechanisms

Cell Division Functions

Neuronal Functions

Signaling Pathways

Expression Patterns

Brain Regional Distribution

Cellular Localization

Developmental Expression

Therapeutic Implications

Targeting KIF14

Therapeutic Strategies

Challenges

Emerging Approaches

Research Tools

Detection Methods

Experimental Models

Genetic and Genomic Resources

Key Interactions Table

See Also

Clinical Implications

Biomarker Potential

Therapeutic Target Validation

Patient Stratification

External Links

References

Summary

💬 Discussion