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CEP152
centrosomal protein 152
CEP152 is located on the long (q) arm of chromosome 15, at band 15q21.1. Arm ratio per GRCh38 - banding schematic.
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Overview
CEP152 encodes a centrosomal protein essential for the accurate duplication of centrioles, the cylindrical structures that form the core of centrosomes. Centrosomes serve as the primary microtubule-organising centres in animal cells, orchestrating spindle formation during mitosis and maintaining cellular architecture. Loss of CEP152 function impairs centriole assembly, resulting in abnormal cell division and developmental defects. Biallelic pathogenic variants in CEP152 are associated with Seckel syndrome, a condition characterised by severe microcephaly, intrauterine growth restriction, and intellectual disability. The gene is located on chromosome 15 and encodes a protein of 1,710 amino acids that recruits key regulators of centriole formation to the centrosome.
What the gene does
The CEP152 protein localises to the proximal end of centrioles and functions as a scaffold for centriole duplication machinery. During the cell cycle, CEP152 recruits polo-like kinase 4 (PLK4), a master regulator of centriole biogenesis, to the centrosome. This recruitment is mediated by a specific interaction domain at the extreme N-terminus of CEP152, enabling PLK4 to phosphorylate downstream targets that initiate the assembly of daughter centrioles. By concentrating PLK4 at the appropriate location, CEP152 ensures that each mother centriole generates exactly one daughter centriole per cell cycle, maintaining the correct number of centrosomes. Beyond centriole duplication, CEP152 contributes to centrosome maturation and the proper organisation of pericentriolar material. Disruption of CEP152 function leads to reduced centriole number, abnormal spindle formation, and genomic instability, particularly affecting rapidly dividing cells during early development.
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Chromosome location
CEP152 is located on the long arm of chromosome 15 at band 15q21.1. The gene spans a genomic region that includes multiple exons encoding the 1,710-amino-acid protein. This chromosomal location places CEP152 within a region containing other genes involved in cellular structure and developmental regulation.
Protein structure
The CEP152 protein comprises 1,710 amino acids with a domain architecture characterised by extensive coiled-coil regions and disordered segments. The N-terminal region (amino acids 1-60) contains the interaction domain for PLK4, which is critical for recruiting this kinase to the centrosome. Multiple disordered regions are present at amino acids 1-27, 39-79, 108-139, 587-611, and 1120-1142, likely providing flexibility for protein-protein interactions. The protein features five prominent coiled-coil domains at amino acids 234-490, 615-664, 700-772, 902-993, and 1170-1241. These coiled-coil structures facilitate oligomerisation and enable CEP152 to serve as a structural scaffold at the centrosome, organising the recruitment of other centriole duplication factors into functional complexes.
Key variants
Pathogenic variants in CEP152 follow an autosomal recessive inheritance pattern, meaning individuals require biallelic variants (one from each parent) to develop associated conditions. Most disease-causing variants are loss-of-function changes, including nonsense mutations, frameshift deletions, and splice-site alterations that abolish protein production or severely disrupt its scaffolding function. The variant landscape reflects the gene's role in centriole duplication, with mutations distributed across the coding sequence.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1613C>G | p.Ser538Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephaly 9, primary, autosomal recessive |
c.2034_2036del | p.Tyr678_Gln679delinsTer | Pathogenic | ★★☆☆ | Microcephaly 9, primary, autosomal recessive |
c.2318G>A | p.Trp773Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Seckel syndrome 5 |
c.3172del | p.Gln1058fs | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephaly 9, primary, autosomal recessive |
c.3925C>T | p.Arg1309Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephaly 9, primary, autosomal recessive |
c.467dup | p.Gln157fs | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephaly 9, primary, autosomal recessive |
c.527G>A | p.Trp176Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephaly 9, primary, autosomal recessive |
c.540+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephaly 9, primary, autosomal recessive |
c.799C>T | p.Arg267Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephaly 9, primary, autosomal recessive |
c.903_904del | p.Glu301fs | Pathogenic/Likely pathogenic | ★★☆☆ | Seckel syndrome 5 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Biallelic pathogenic variants in CEP152 cause Seckel syndrome, a rare autosomal recessive disorder characterised by severe microcephaly, intrauterine growth restriction, and proportionate short stature. Affected individuals typically present with a head circumference more than three standard deviations below the mean at birth, distinctive facial features including a prominent nose and receding forehead, and moderate to severe intellectual disability. The condition reflects the critical requirement for CEP152 in normal brain development, where proper centriole duplication is essential for the symmetric cell divisions that generate cortical neurons.
- Seckel syndrome Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic CEP152 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
CEP152 is included on several NHS Genomic Medicine Service gene panels with green classification, indicating strong evidence for clinical validity. The gene appears on the DDG2P panel, the Fetal Anomalies panel (R21), the Intellectual Disability panel (R29), and the Severe Microcephaly panel (R88). These panel memberships reflect the gene's established role in neurodevelopmental conditions presenting with microcephaly and growth restriction, supporting its use in diagnostic testing for individuals with relevant clinical features.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
How is CEP152-related Seckel syndrome inherited?
Seckel syndrome caused by CEP152 variants follows autosomal recessive inheritance. An affected individual inherits one pathogenic variant from each parent, who are typically unaffected carriers. Each child of two carrier parents has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of inheriting neither variant.
What is the role of CEP152 at the centrosome?
CEP152 functions as a scaffold protein that recruits polo-like kinase 4 to the centrosome, enabling the controlled duplication of centrioles during each cell cycle. By organising this molecular machinery, CEP152 ensures cells maintain the correct number of centrosomes required for normal cell division.
Can CEP152 variants be identified through NHS testing?
Yes, CEP152 is included on multiple NHS Genomic Medicine Service panels with green classification, indicating it can be tested as part of diagnostic gene panels for severe microcephaly, intellectual disability, and foetal anomalies when clinical features suggest a relevant condition.