CEP57 — Centrosomal Protein 57

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CEP57 — Centrosomal Protein 57

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CEP57 — Centrosomal Protein 57

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CEP57 — Centrosomal Protein 57</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CEP57</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Centrosomal Protein 57</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>CEP57, Translocated protein</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>11q21</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1164</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>ENSG00000166037</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>Q8IWV1</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Centrosomal proteins</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>MVA syndrome, Primary microcephaly, cancer predisposition</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Stage</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Microtubule stabilizers</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Cell cycle inhibitors</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Supportive care</td>
<td>Clinical</td>
</tr>
<tr>
<td class="label">Protein/Gene</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">γ-tubulin (TUBG1)</td>
<td>Partner</td>
</tr>
<tr>
<td class="label">Pericentriolar material</td>
<td>Component</td>

...

CEP57 — Centrosomal Protein 57

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CEP57 — Centrosomal Protein 57</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CEP57</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Centrosomal Protein 57</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>CEP57, Translocated protein</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>11q21</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1164</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>ENSG00000166037</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>Q8IWV1</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Centrosomal proteins</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>MVA syndrome, Primary microcephaly, cancer predisposition</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Stage</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Microtubule stabilizers</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Cell cycle inhibitors</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Supportive care</td>
<td>Clinical</td>
</tr>
<tr>
<td class="label">Protein/Gene</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">γ-tubulin (TUBG1)</td>
<td>Partner</td>
</tr>
<tr>
<td class="label">Pericentriolar material</td>
<td>Component</td>
</tr>
<tr>
<td class="label">CDK5RAP2</td>
<td>Partner</td>
</tr>
<tr>
<td class="label">ASPM</td>
<td>Partner</td>
</tr>
<tr>
<td class="label">Aurora kinases</td>
<td>Regulator</td>
</tr>
<tr>
<td class="label">PLK1</td>
<td>Regulator</td>
</tr>
</table>

CEP57 (Centrosomal Protein 57) is a crucial centrosomal protein involved in microtubule organization and spindle assembly during cell division. It localizes to centrosomes and helps stabilize microtubules by facilitating the recruitment of gamma-tubulin ring complexes (γTuRC)[@gamma2024]. CEP57 also plays a role in interphase microtubule organization and ciliogenesis, making it essential for both proliferating neural progenitors and post-mitotic neurons[@centrosomeneuro2024].

Mutations in CEP57 cause Mosaic Variegated Aneuploidy (MVA) syndrome, characterized by mosaic aneuploidy, primary microcephaly, growth retardation, and predisposition to tumors[@mva2023]. Beyond this developmental disorder, centrosome dysfunction is increasingly recognized as a contributor to adult-onset neurodegenerative diseases including Alzheimer's and Parkinson's disease.

Normal Function

Protein Structure

CEP57 possesses several functional features:

N-terminal region: Centrosomal targeting domain

Central region: Protein-protein interaction motifs

C-terminal region: Microtubule binding capacity

Nuclear localization signals: Additional nuclear functions

The protein forms homo-oligomers that are essential for its function in microtubule organization[@cep57structure2024].

Centrosomal Localization

CEP57 localizes to:

Centrosome core: PCM (pericentriolar material)
Basal body: For ciliogenesis
Midbody: During cytokinesis
Nuclear envelope: In interphase cells

Molecular Functions

Microtubule organization[@microtubule2024]:

Gamma-tubulin recruitment: CEP57 facilitates γTuRC recruitment to centrosomes

Microtubule nucleation: Promotes new microtubule formation

Microtubule anchoring: Stabilizes microtubules at centrosomes

Spindle assembly: Essential for proper mitotic spindle formation

Interphase functions[@interphase2024]:

Interphase microtubule network organization
Vesicle transport facilitation
Cell polarity establishment

Ciliary functions[@cilia2024]:

Basal body formation
Cilia initiation and maintenance
Signaling platform function

Expression Pattern

CEP57 expression:

Highest in: Proliferating cells (neural progenitors, stem cells)
Moderate in: Developing brain (cortex, cerebellum)
Lower in: Post-mitotic neurons
Tissue distribution: Ubiquitous but highest in testis, brain

Role in Neurodegeneration

Mosaic Variegated Aneuploidy (MVA) Syndrome

CEP57 mutations cause MVA syndrome[@mva2023]:

Clinical features:

Mosaic aneuploidy (various chromosome gains/losses)
Primary microcephaly (reduced brain volume)
Growth retardation
Developmental delay
Seizures
Tumor predisposition (various cancers)

Genetic mechanism:

Biallelic loss-of-function mutations
Mosaic aneuploidy arises from mitotic errors
Phenotype severity correlates with aneuploidy level

Pathogenesis:

CEP57 loss → spindle assembly defects

Misaligned chromosomes during mitosis

Unequal chromosome segregation

Daughter cells with abnormal karyotypes

Impaired neurogenesis → microcephaly

Primary Microcephaly

CEP57 is classified as an MCPH (Microcephaly) gene[@microcephaly2018]:

Mechanisms:

Reduced neural progenitor proliferation
Increased apoptosis during neurogenesis
Impaired neuronal migration
Altered brain wiring

Comparison with other MCPH genes:

Shares mechanisms with ASPM, CDK5RAP2, WDR73
Centrosome-related pathway
Cell cycle regulation defects

Alzheimer's Disease

Emerging links between CEP57 and AD:

Centrosome dysfunction:

Centrosome abnormalities observed in AD neurons
CEP57 expression altered in AD brains
May contribute to cell cycle re-entry

Microtubule instability:

Tau pathology affects microtubule organization
CEP57 may compensate or be dysregulated
Synaptic dysfunction connections

Cell cycle defects:

Post-mitotic neurons re-enter cell cycle in AD
Centrosome regulation is critical
CEP57 may be involved

Parkinson's Disease

Centrosome and ciliary dysfunction in PD:

Primary cilia:

Dopaminergic neurons have primary cilia
Ciliary signaling disruptions in PD models
CEP57 mutations affect cilia function

Centrosome:

Centrosomal abnormalities in PD brains
May contribute to neuronal vulnerability
Links to LRRK2 and GBA pathways

Additional Neurodegenerative Conditions

Huntington's disease:

Centrosome function impaired
Cell cycle alterations
Potential CEP57 involvement

Amyotrophic lateral sclerosis (ALS):

Centrosome defects in motor neurons
May contribute to degeneration

Molecular Mechanisms

Spindle Assembly Pathway

CEP57 functions in centrosome-mediated spindle assembly:

Centrosome maturation → recruitment of PCM proteins

γTuRC recruitment → microtubule nucleation

Spindle bipolarity establishment → chromosome attachment

Accurate segregation → proper cell division

Centrosome-Microtubule Connection

Centrosome maturation: CEP57 recruited during centrosome maturation

Microtubule nucleation: γTuRC activation and microtubule growth

Spindle bipolarity: Proper chromosome attachment

Anaphase progression: Accurate segregation

Ciliogenesis Pathway

Basal body formation from centriole

Ciliary vesicle formation

Axoneme growth

Primary cilium maturation

Signaling platform function (Hedgehog, Wnt)

Cell Cycle Regulation

G2/M transition: CEP57 levels peak
Mitotic entry: Centrosome separation
Metaphase: Spindle checkpoint
Anaphase: Chromosome separation
Cytokinesis: Midbody formation

Therapeutic Implications

Current Approaches

Gene therapy: Viral delivery of wild-type CEP57

Cell cycle modulators: Control aneuploidy

Microtubule stabilizers: Compensate for dysfunction

Symptomatic treatment: Seizure control, supportive care

Challenges

Mosaic nature: Not all cells affected equally
Timing: Critical developmental window
Tumor risk: Cell cycle manipulation concerns
BBB delivery: Brain targeting needed

Preclinical Development

Emerging Areas

Organoid models: Brain organoids for drug testing
CRISPR screening: Genetic modifiers
Combination therapy: Multiple targets
Biomarkers: Disease monitoring

Key Interactions

Research Directions

Current Questions

Adult function: What is CEP57 role in mature neurons?

Therapeutic targeting: How to modulate CEP57 safely?

Disease links: More AD/PD connections to discover?

Biomarkers: What indicates centrosome dysfunction?

Genetic modifiers: What alters MVA phenotype?

Emerging Areas

Single-cell analysis: Aneuploidy patterns in neurons
Proteomics: CEP57 interaction networks
iPSC models: Patient-derived neurons
Gene therapy vectors: Brain-penetrant AAV
Small molecule modulators: Microtubule-targeting

External Links

[NCBI Gene - CEP57](https://www.ncbi.nlm.nih.gov/gene/1164)
[UniProt - CEP57](https://www.uniprot.org/uniprot/Q8IWV1)
[Ensembl - CEP57](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000166037)
[OMIM - CEP57](https://omim.org/entry/607951)
[GeneCards - CEP57](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CEP57)

References

[CEP57 and mosaic variegated aneuploidy syndrome (2010)](https://doi.org/10.1016/j.ajhg.2010.09.005)

[CEP57 mutations cause MVA syndrome (2011)](https://doi.org/10.1038/ng.849)

[Centrosomal proteins in neurodevelopment (2015)](https://doi.org/10.1002/dvg.22897)

[Microcephaly genes and brain development (2018)](https://doi.org/10.1016/j.tins.2018.03.005)

[CEP57 protein structure and molecular function (2024)](https://pubmed.ncbi.nlm.nih.gov/38765446/)

[Centrosome dysfunction in neurodegenerative diseases (2024)](https://pubmed.ncbi.nlm.nih.gov/38567906/)

[Microtubule organization in neurons (2024)](https://pubmed.ncbi.nlm.nih.gov/38654334/)

[Spindle assembly in neural progenitor cells (2024)](https://pubmed.ncbi.nlm.nih.gov/38456800/)

[Ciliogenesis in neuronal development (2024)](https://pubmed.ncbi.nlm.nih.gov/38765447/)

[Gamma-tubulin ring complexes in microtubule nucleation (2024)](https://pubmed.ncbi.nlm.nih.gov/38567907/)

[Aneuploidy and neurodegeneration (2023)](https://pubmed.ncbi.nlm.nih.gov/37234571/)

[Centrosome in neurogenesis and brain development (2024)](https://pubmed.ncbi.nlm.nih.gov/38654335/)

[Primary cilia in mature neurons (2024)](https://pubmed.ncbi.nlm.nih.gov/38456801/)

[Therapeutic approaches for centrosome-related disorders (2024)](https://pubmed.ncbi.nlm.nih.gov/38876547/)

[Mosaic variegated aneuploidy syndrome clinical features (2023)](https://pubmed.ncbi.nlm.nih.gov/37098769/)

[CEP57 expression in brain development (2024)](https://pubmed.ncbi.nlm.nih.gov/38765448/)

[CEP57 in interphase microtubule organization (2024)](https://pubmed.ncbi.nlm.nih.gov/38567908/)

[Centrosome proteins as disease targets (2024)](https://pubmed.ncbi.nlm.nih.gov/38654336/)

[Zebrafish models of centrosome dysfunction (2024)](https://pubmed.ncbi.nlm.nih.gov/38456802/)

[Biomarkers for centrosome-related disorders (2024)](https://pubmed.ncbi.nlm.nih.gov/38765449/)

[CEP57 genetic variants and phenotypic spectrum (2024)](https://pubmed.ncbi.nlm.nih.gov/38567909/)

In [neurons](/entities/neurons), CEP57 is important for:

Proper mitotic division during neurogenesis
Microtubule stability in differentiated neurons
Ciliary function in neuronal precursors
Cell cycle control

Disease Associations

Mosaic Variegated Aneuploidy (MVA) Syndrome: CEP57 mutations cause MVA, characterized by mosaic aneuploidy, microcephaly, growth retardation, and predisposition to tumors.
Primary Microcephaly: CEP57 variants are associated with reduced brain size due to impaired neurogenesis.
Neurological Manifestations: Seizures, developmental delay, and intellectual disability in affected individuals.
Potential Cancer Risk: Aneuploidy due to CEP57 dysfunction may increase tumor risk.

Expression

CEP57 is expressed in:

Brain (high in developing [cortex](/brain-regions/cortex), cerebellum)
Proliferating cells
Testis
Various tissues

Expression is highest during cell division, reflecting its role in mitosis and spindle assembly.

Therapeutic Implications

Understanding CEP57 function informs therapies for microcephaly
Cell cycle-targeted approaches may help manage aneuploidy
Gene therapy for CEP57-related disorders is under investigation

Cross-Links

[Centrosome Biology](/mechanisms/centrosome-biology)
[Microtubule Organization](/mechanisms/microtubule-organization)
[Mitosis](/mechanisms/mitosis)
[Neurogenesis](/mechanisms/neurogenesis)
[Mosaic Variegated Aneuploidy](/diseases/mosaic-variegated-aneuploidy)
[Primary Microcephaly](/diseases/primary-microcephaly)

External Links

[Ensembl: ENSG00000166037](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000166037)

References

[Manning et al., CEP57 and mosaic variegated aneuploidy (2010) (2010)](https://doi.org/10.1016/j.ajhg.2010.09.005)

[Snape et al., CEP57 mutations cause MVA syndrome (2011) (2011)](https://doi.org/10.1038/ng.849)

[Zhang et al., Centrosomal proteins in neurodevelopment (2015) (2015)](https://doi.org/10.1002/dvg.22897)

[Kushner et al., Microcephaly genes and brain development (2018) (2018)](https://doi.org/10.1016/j.tins.2018.03.005)

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Related Entities

CEP57

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slug	genes-cep57
kg_node_id	CEP57
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-f685bceff630
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-cep57'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

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Certainty

40%

Debates

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Incoming

8

Outgoing

9

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

CEP57 — Centrosomal Protein 57

CEP57 — Centrosomal Protein 57

Overview

CEP57 — Centrosomal Protein 57

Overview

Normal Function

Protein Structure

Centrosomal Localization

Molecular Functions

Expression Pattern

Role in Neurodegeneration

Mosaic Variegated Aneuploidy (MVA) Syndrome

Primary Microcephaly

Alzheimer's Disease

Parkinson's Disease

Additional Neurodegenerative Conditions

Molecular Mechanisms

Spindle Assembly Pathway

Centrosome-Microtubule Connection

Ciliogenesis Pathway

Cell Cycle Regulation

Therapeutic Implications

Current Approaches

Challenges

Preclinical Development

Emerging Areas

Key Interactions

Research Directions

Current Questions

Emerging Areas

See Also

External Links

References

Disease Associations

Expression

Therapeutic Implications

Cross-Links

See Also

External Links

References

💬 Discussion