CEP164 — Centrosomal Protein 164

CEP164 — Centrosomal Protein 164

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f8f9fa;text-align:center;font-size:1.1em;">CEP164</th></tr>
<tr><th>Symbol</th><td>CEP164</td></tr>
<tr><th>Full Name</th><td>Centrosomal Protein 164</td></tr>
<tr><th>Chromosome</th><td>11q13.2</td></tr>
<tr><th>NCBI Gene ID</th><td>[55107](https://www.ncbi.nlm.nih.gov/gene/55107)</td></tr>
<tr><th>OMIM</th><td>[614848](https://www.omim.org/entry/614848)</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000110237](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110237)</td></tr>
<tr><th>UniProt</th><td>[Q8WU02](https://www.uniprot.org/uniprot/Q8WU02)</td></tr>
<tr><th>Associated Diseases</th><td>[Nephronophthisis](/diseases/nephronophthisis), [Joubert syndrome](/diseases/joubert-syndrome), [Senior-Loken syndrome](/diseases/senior-loken-syndrome)</td></tr>
</table>
</div>

Overview

CEP164 (Centrosomal Protein 164) is a critical component of the centrosome and primary cilia, serving as a master regulator of ciliogenesis and cell cycle progression [graber2007](https://pubmed.ncbi.nlm.nih.gov/17227893/). Located at the distal appendages of the mother centriole, CEP164 functions as a molecular scaffold that recruits essential ciliary proteins and coordinates vesicle trafficking to the forming cilium [gomez-ferrero2012](https://pubmed.ncbi.nlm.nih.gov/23263379/).

CEP164 — Centrosomal Protein 164

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f8f9fa;text-align:center;font-size:1.1em;">CEP164</th></tr>
<tr><th>Symbol</th><td>CEP164</td></tr>
<tr><th>Full Name</th><td>Centrosomal Protein 164</td></tr>
<tr><th>Chromosome</th><td>11q13.2</td></tr>
<tr><th>NCBI Gene ID</th><td>[55107](https://www.ncbi.nlm.nih.gov/gene/55107)</td></tr>
<tr><th>OMIM</th><td>[614848](https://www.omim.org/entry/614848)</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000110237](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110237)</td></tr>
<tr><th>UniProt</th><td>[Q8WU02](https://www.uniprot.org/uniprot/Q8WU02)</td></tr>
<tr><th>Associated Diseases</th><td>[Nephronophthisis](/diseases/nephronophthisis), [Joubert syndrome](/diseases/joubert-syndrome), [Senior-Loken syndrome](/diseases/senior-loken-syndrome)</td></tr>
</table>
</div>

Overview

CEP164 (Centrosomal Protein 164) is a critical component of the centrosome and primary cilia, serving as a master regulator of ciliogenesis and cell cycle progression [graber2007](https://pubmed.ncbi.nlm.nih.gov/17227893/). Located at the distal appendages of the mother centriole, CEP164 functions as a molecular scaffold that recruits essential ciliary proteins and coordinates vesicle trafficking to the forming cilium [gomez-ferrero2012](https://pubmed.ncbi.nlm.nih.gov/23263379/).

Beyond its ciliary functions, CEP164 plays a vital role in the DNA damage response through ATM-dependent signaling [burke2014](https://pubmed.ncbi.nlm.nih.gov/24837433/). Mutations in CEP164 cause nephronophthisis (NPHP) and related ciliopathies, while emerging research suggests connections between ciliary dysfunction and neurodegenerative diseases including [Alzheimer's disease](/diseases/alzheimers-disease) and [Parkinson's disease](/diseases/parkinsons-disease) [yuan2019](https://pubmed.ncbi.nlm.nih.gov/31362721/), [cheng2019](https://pubmed.ncbi.nlm.nih.gov/30623315/).

Gene and Protein Structure

Gene Organization

The CEP164 gene is located on chromosome 11q13.2 and encodes a protein of 1463 amino acids with a molecular weight of approximately 164 kDa. The gene contains 37 exons and spans approximately 26 kb of genomic DNA.

Protein Domains

The CEP164 protein contains several functional domains:

Subcellular Localization

Biological Functions

Ciliogenesis

CEP164 is essential for primary cilia formation [siller2017](https://pubmed.ncbi.nlm.nih.gov/28238654/):

Cell Cycle Regulation

CEP164 regulates cell cycle progression through multiple mechanisms [tooley2011](https://pubmed.ncbi.nlm.nih.gov/21444685/):

• Centrosome maturation: Promotes centrosome separation and maturation
• Spindle assembly: Ensures proper mitotic spindle formation
• G1/S transition: Controls entry into S phase
• G2/M checkpoint: Participates in DNA damage checkpoints

DNA Damage Response

CEP164 participates in ATM-mediated DNA damage response [burke2014](https://pubmed.ncbi.nlm.nih.gov/24837433/):

• ATM phosphorylation of CEP164 at serine 328
• Recruitment of DNA repair proteins to damage sites
• Cell cycle arrest upon DNA damage
• Connection to p53 tumor suppressor pathway

Ciliary Signaling Pathways

Primary cilia serve as signaling hubs [satir2010](https://pubmed.ncbi.nlm.nih.gov/20534742/), [potter2011](https://pubmed.ncbi.nlm.nih.gov/21358643/):

| Pathway | Function | Neuronal Relevance |
|---------|----------|-------------------|
| Hedgehog | Development, cell fate | Neurogenesis |
| Wnt | Planar cell polarity | Brain patterning |
| PDGF | Cell proliferation | Neurogenesis |
| Notch | Cell fate decisions | Differentiation |

Role in Neurodegenerative Diseases

Alzheimer's Disease

Emerging evidence links ciliary dysfunction to [Alzheimer's disease](/diseases/alzheimers-disease) [yuan2019](https://pubmed.ncbi.nlm.nih.gov/31362721/):

• Centrosome abnormalities: Altered centrosome morphology in AD brain
• Ciliary signaling disruption: Impaired Hedgehog and Wnt signaling
• Cell cycle re-entry: Neurons attempt to re-enter cell cycle
• DNA damage accumulation: Impaired DNA repair in neurons

• Neuronal polarity establishment
• Axonal transport
• Synaptic function
• Protein trafficking

Parkinson's Disease

Ciliary dysfunction may contribute to [Parkinson's disease](/diseases/parkinsons-disease) [cheng2019](https://pubmed.ncbi.nlm.nih.gov/30623315/):

• Primary cilia in dopaminergic neurons: Cilia regulate dopamine signaling
• Ciliary signaling disruption: Hedgehog pathway alterations
• Cellular stress response: Cilia as mechanosensors
• Autophagy-lysosomal pathways: Connection to protein aggregation

Other Neurodegenerative Conditions

• Huntington's disease: Ciliary dysfunction in striatal neurons
• Amyotrophic lateral sclerosis: Altered centrosome function in motor neurons
• Retinal degeneration: CEP164 mutations affect photoreceptor cilia

Disease Associations

Nephronophthisis (NPHP)

CEP164 mutations cause NPHP [chaki2012](https://pubmed.ncbi.nlm.nih.gov/22633075/), a recessive cystic kidney disease:

• NPHP type 15: CEP164 is the causative gene
• Kidney pathology: Tubulointerstitial fibrosis, cyst formation
• Age of onset: Childhood to adolescence
• Extra-renal manifestations: Include neurological symptoms

Senior-Loken Syndrome

CEP164 variants can cause this syndrome:

• NPHP combined with retinal dystrophy
• Neurological involvement: Developmental delay, ataxia
• Treatment: Kidney transplant for ESRD

Joubert Syndrome

Some CEP164 variants are associated with [Joubert syndrome](/diseases/joubert-syndrome):

• Molar tooth sign on MRI
• Cerebellar and brainstem malformations
• Developmental delay
• Occulomotor apraxia

Ciliopathies

CEP164-related disorders fall into the ciliopathy spectrum [slaats2015](https://pubmed.ncbi.nlm.nih.gov/25937498/):

| Disorder | CEP164 Role | Phenotype |
|----------|-------------|-----------|
| NPHP | Causative | Kidney cysts, fibrosis |
| Senior-Loken | Causative | NPHP + retinal degeneration |
| Joubert | Associated | Cerebellar malformation |
| Meckel syndrome | Possible | Encephalocele, polydactyly |

Expression Patterns

Tissue Distribution

CEP164 shows broad expression:

• Kidney: Tubular epithelial cells (highest)
• Retina: Photoreceptor cells
• Brain: [Cortex](/brain-regions/cortex), [cerebellum](/brain-regions/cerebellum), [hippocampus](/brain-regions/hippampus)
• Lung: Respiratory epithelium
• Testis: Spermatogenic cells
• Various epithelia: Throughout the body

Brain Regional Distribution

Within the nervous system [braun2015](https://pubmed.ncbi.nlm.nih.gov/26299312/):

• Cerebral cortex: Pyramidal neurons
• Hippocampus: Dentate gyrus, CA regions
• Cerebellum: Purkinje cells
• Subventricular zone: Neural stem cells
• Olfactory bulb: Sensory neurons

Cell Type Specificity

• Neurons: Expression in excitatory and inhibitory neurons
• Astrocytes: Moderate expression
• Oligodendrocytes: Lower expression
• Neural progenitors: High expression during development
• Microglia: Minimal expression

Therapeutic Implications

Targeting Ciliary Function

Modulating CEP164 and ciliary pathways represents a therapeutic strategy [ibanez-tallon2019](https://pubmed.ncbi.nlm.nih.gov/30610214/):

Ciliary Enhancement

• Small molecules: Promote ciliogenesis
• Gene therapy: Deliver functional CEP164
• Protein replacement: Recombinant protein delivery

Signaling Pathway Modulation

• Hedgehog modulators: Smoothened agonists/antagonists
• Wnt pathway: Beta-catenin modulators
• Cyclic AMP: ciliary signaling regulation

Neurodegeneration Strategies

Drug Development Considerations

| Challenge | Approach |
|-----------|----------|
| BBB penetration | Target CNS-penetrant molecules |
| Protein delivery | Viral vectors for gene therapy |
| Specificity | Target ciliary-specific pathways |
| Timing | Early intervention in disease |

Existing Research

• Ciliary modulators in clinical trials for other conditions
• Gene therapy approaches for inherited ciliopathies
• Small molecule enhancers of ciliary signaling

Animal Models

Knockout Studies

• Cep164 knockout mice: Embryonic lethal
• Conditional knockouts: Tissue-specific phenotypes
• Zebrafish models: Ciliary dysfunction phenotypes

Disease Models

• NPHP mouse models with Cep164 mutations
• Ciliary dysfunction models for neurodegeneration
• Centrosome ablation studies

Research Directions

Unresolved Questions

Emerging Areas

Cross-Links

Related Mechanisms

• [Primary Cilia in Neurodegeneration](/mechanisms/primary-cilia-neurodegeneration)
• [Centrosome Biology](/mechanisms/centrosome-biology)
• [DNA Damage Response in Neurodegeneration](/mechanisms/dna-damage-response)
• [Ciliary Signaling Pathways](/mechanisms/ciliary-signaling)

Related Genes

• [CEP290](/genes/cep290) — Related ciliary protein
• [NPHP1](/genes/nphp1) — NPHP1, nephronophthisis
• [RPGRIP1L](/genes/rpgripl) — Ciliary protein

Related Diseases

• [Nephronophthisis](/diseases/nephronophthisis)
• [Joubert Syndrome](/diseases/joubert-syndrome)
• [Senior-Loken Syndrome](/diseases/senior-loken-syndrome)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [NCBI Gene: CEP164](https://www.ncbi.nlm.nih.gov/gene/55107)
• [UniProt: Q8WU02](https://www.uniprot.org/uniprot/Q8WU02)
• [Ensembl: ENSG00000110237](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000110237)
• [HGNC: CEP164](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:29128)

References