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:
N-terminal coiled-coil domain: Mediates protein-protein interactions and dimerization
Central proline-rich region: Contains potential phosphorylation sites
C-terminal domains: Responsible for centriolar localization and microtubule binding
WD40 repeat region: Functions in protein-protein interactionsSubcellular Localization
Mermaid diagram (expand to render)
Biological Functions
Ciliogenesis
CEP164 is essential for primary cilia formation [siller2017](https://pubmed.ncbi.nlm.nih.gov/28238654/):
Distal appendage anchoring: CEP164 localizes to the distal appendages of the mother centriole
Vesicle recruitment: Recruits ciliary vesicles to the centrosome
Membrane docking: Facilitates fusion of vesicles with the plasma membrane
Axoneme extension: Supports elongation of the ciliary axonemeCell 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
The centrosome plays critical roles in:
- 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
Restore ciliary function: Enhance CEP164 activity
Protect centrosome: Prevent centrosome stress
Enhance DNA repair: Support genomic integrity
Modulate signaling: Normalize ciliary pathwaysDrug 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
Ciliary-specific functions: How CEP164 differs from other centriolar proteins
Neuronal roles: Specific functions in neurons vs. other cell types
Therapeutic targeting: How to specifically modulate CEP164Emerging Areas
Cryo-EM studies: CEP164 structure at atomic resolution
Single-cell analysis: CEP164 in specific neuronal populations
Ciliary organoids: Brain organoid models
Proteomics: CEP164 interaction networksCross-Links
- [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)
- [CEP290](/genes/cep290) — Related ciliary protein
- [NPHP1](/genes/nphp1) — NPHP1, nephronophthisis
- [RPGRIP1L](/genes/rpgripl) — Ciliary protein
- [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
[Graser A, et al. CEP164 regulates cell cycle progression and DNA damage response. J Cell Biol. 2007](https://pubmed.ncbi.nlm.nih.gov/17227893/)
[Chaki M, et al. Exome sequencing identifies CEP164 mutations in NPHP. Nat Genet. 2012](https://pubmed.ncbi.nlm.nih.gov/22633075/)
[Slaats GG, et al. CEP164 and ciliopathies: connecting the dots. Trends Genet. 2015](https://pubmed.ncbi.nlm.nih.gov/25937498/)
[Wheway G, et al. The ciliary protein CEP164 in development and disease. Hum Mol Genet. 2019](https://pubmed.ncbi.nlm.nih.gov/31125081/)
[Gomez-Ferrerio MA, et al. CEP164 anchors microtubule nucleation at the centrosome. Nat Cell Biol. 2012](https://pubmed.ncbi.nlm.nih.gov/23263379/)
[Schmidt KN, et al. CEP164 mutation causes NPHP. Nat Genet. 2012](https://pubmed.ncbi.nlm.nih.gov/22633076/)
[Siller SS, et al. CEP164 in ciliary vesicle trafficking. Dev Cell. 2017](https://pubmed.ncbi.nlm.nih.gov/28238654/)
[Burke JE, et al. CEP164 and the DNA damage response. Cell Cycle. 2014](https://pubmed.ncbi.nlm.nih.gov/24837433/)
[Tooley M, et al. CEP164 in centriole appendage formation. J Cell Biol. 2011](https://pubmed.ncbi.nlm.nih.gov/21444685/)
[Potter VL, et al. Primary cilia in neuronal signaling. Nat Rev Neurosci. 2011](https://pubmed.ncbi.nlm.nih.gov/21358643/)
[Lara J, et al. Ciliary dysfunction in neurodegeneration. Front Cell Neurosci. 2020](https://pubmed.ncbi.nlm.nih.gov/33013385/)
[Ibanez-Tallon I, et al. Primary cilia and neurological disease. Nat Rev Neurol. 2019](https://pubmed.ncbi.nlm.nih.gov/30610214/)
[Yuan S, et al. CEP164 in Alzheimer's disease. Acta Neuropathol Commun. 2019](https://pubmed.ncbi.nlm.nih.gov/31362721/)
[Cheng CY, et al. Cilia and Parkinson's disease. Mov Disord. 2019](https://pubmed.ncbi.nlm.nih.gov/30623315/)
[Satir P, et al. Primary ciliary structure and function. Cold Spring Harb Perspect Biol. 2010](https://pubmed.ncbi.nlm.nih.gov/20534742/)
[Fliegauf M, et al. Molecular basis of ciliary function. Nat Rev Mol Cell Biol. 2007](https://pubmed.ncbi.nlm.nih.gov/17534527/)
[Braun DA, et al. Ciliary signaling in brain development. Dev Biol. 2015](https://pubmed.ncbi.nlm.nih.gov/26299312/)
[Sahab S, et al. CEP164 and sonic hedgehog signaling. Development. 2014](https://pubmed.ncbi.nlm.nih.gov/25209246/)
[Yang Y, et al. Centrosome abnormalities in cancer. Nat Rev Cancer. 2018](https://pubmed.ncbi.nlm.nih.gov/30237576/)
[Valente EM, et al. Primary cilia in kidney disease. Nat Rev Nephrol. 2013](https://pubmed.ncbi.nlm.nih.gov/24247183/)
[Rana A, et al. Ciliary beat frequency in respiratory epithelium. Am J Physiol Lung Cell Mol Physiol. 2019](https://pubmed.ncbi.nlm.nih.gov/31162921/)