On this page
CEP120
centrosomal protein 120
CEP120 is located on the long (q) arm of chromosome 5, at band 5q23.2. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 5 in the library →Available at Jeen Health
Clinical tests that include this
Overview
CEP120 encodes centrosomal protein 120, a structural protein localised to the centrosome, the cell's major microtubule-organising centre. The centrosome plays a critical role in cell division, ensuring chromosomes separate correctly, and in the assembly of primary cilia, antenna-like structures that cells use to sense their environment. Pathogenic changes in CEP120 impair these processes, resulting in a range of ciliopathy conditions characterised by skeletal abnormalities, intellectual disability, and structural brain malformations. The gene is recognised across multiple NHS Genomic Medicine Service panels for skeletal dysplasias, ciliopathies, and neurodevelopmental disorders, reflecting its importance in clinical diagnostics.
What the gene does
Centrosomal protein 120 functions as a structural scaffold within the centrosome, orchestrating the duplication of centrioles during each cell cycle. Centrioles are cylindrical structures that form the core of the centrosome and serve as templates for building new centrioles, ensuring each daughter cell inherits the correct number. CEP120 interacts with other centrosomal proteins to stabilise nascent centrioles and regulate their maturation. Beyond cell division, CEP120 is essential for ciliogenesis, the process by which cells construct primary cilia. These microtubule-based projections extend from the cell surface and act as sensory organelles, detecting chemical signals and mechanical cues from the surrounding environment. Disruption of CEP120 function compromises both centriole duplication and cilia assembly, leading to defects in cellular signalling pathways that govern skeletal patterning, brain development, and organ formation during embryogenesis and postnatal growth.
Video: Genetics 101
Chromosome location
CEP120 is located on the long arm of chromosome 5 at position 23.2, designated as 5q23.2. The gene spans multiple exons encoding a protein of 986 amino acids. This chromosomal region contains several other genes involved in developmental processes, though CEP120 itself is the primary gene in this locus associated with ciliopathy phenotypes.
Protein structure
The 986-amino-acid CEP120 protein contains two C2 domains: C2 1 spans amino acids 1 to 112, whilst C2 2 extends from amino acids 433 to 566. C2 domains typically mediate protein-protein interactions and membrane association, suggesting CEP120 engages with other centrosomal components through these regions. The protein includes disordered regions from amino acids 350 to 424 and 914 to 937, which may confer flexibility for dynamic interactions during centriole assembly. A prominent coiled-coil domain occupies amino acids 669 to 925, characteristic of proteins that form elongated structural scaffolds or participate in oligomerisation. This domain architecture reflects CEP120's role as a structural organiser within the centrosome.
Key variants
Pathogenic variants in CEP120 follow both autosomal recessive and autosomal dominant inheritance patterns, depending on the specific variant and associated phenotype. Loss-of-function variants typically cause recessive conditions, requiring two altered copies for disease manifestation, whilst certain dominant-negative variants can cause features with only one altered copy. Variants span the gene and include missense changes affecting critical functional domains, frameshift and nonsense variants leading to truncated protein products, and splice-site alterations disrupting normal transcript processing.
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.1397del | p.Leu466fs | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome 31 |
c.1615A>T | p.Lys539Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Short-rib thoracic dysplasia 13 with or without polydactyly |
c.2323C>T | p.Gln775Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Short-rib thoracic dysplasia 13 with or without polydactyly |
c.595G>C | p.Ala199Pro | Pathogenic/Likely pathogenic | ★★☆☆ | Short-rib thoracic dysplasia 13 with or without polydactyly |
c.116T>A | p.Leu39Ter | Pathogenic | ★☆☆☆ | CEP120-related disorder |
c.1175C>G | p.Ser392Ter | Pathogenic | ★☆☆☆ | Short-rib thoracic dysplasia 13 with or without polydactyly |
c.1789_1792del | p.Ser597fs | Pathogenic | ★☆☆☆ | Short-rib thoracic dysplasia 13 with or without polydactyly |
c.2026G>T | p.Glu676Ter | Pathogenic | ★☆☆☆ | Short-rib thoracic dysplasia 13 with or without polydactyly |
c.2548C>T | p.Arg850Ter | Pathogenic | ★☆☆☆ | Short-rib thoracic dysplasia 13 with or without polydactyly |
c.674_675insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTCTTTTACTACTCTTT | p.Leu225delinsPhePhePhePhePhePhePheXaaXaaXaaXaaThrSerTer | Pathogenic | ★☆☆☆ | Short-rib thoracic dysplasia 13 with or without polydactyly |
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
CEP120-related disorders encompass a spectrum of skeletal ciliopathies and neurodevelopmental conditions. Affected individuals may present with short-rib thoracic dysplasia, characterised by a narrow chest and shortened ribs, alongside limb abnormalities and variable neurodevelopmental involvement. Brain malformations such as Joubert syndrome features, including the characteristic molar tooth sign on brain imaging, have been documented in some cases. The phenotypic spectrum reflects the gene's dual role in skeletal patterning through ciliary signalling and in brain development through centrosomal function during neurogenesis. Severity ranges from perinatal lethality in severe skeletal forms to milder presentations with intellectual disability and subtle skeletal findings.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic CEP120 variants typically follow ar/ad 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
CEP120 holds green classification status across multiple NHS Genomic Medicine Service gene panels, indicating strong evidence for its role in the listed conditions. The gene appears on the Fetal Anomalies panel (R21), Intellectual Disability panel (R29), Rare Multisystem Ciliopathy Disorders panel, Skeletal Ciliopathies panel, Skeletal Dysplasia panel (R104), and Thoracic Dystrophies panel. This extensive panel representation reflects the broad clinical impact of CEP120 variants and ensures the gene is included in genomic testing for patients presenting with relevant clinical features within the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
How is CEP120 inherited?
CEP120-related conditions can follow either autosomal recessive or autosomal dominant inheritance patterns. In autosomal recessive cases, an individual inherits two altered gene copies, one from each parent, who are typically unaffected carriers. Some variants may act in a dominant manner, causing features with only one altered copy.
What is a ciliopathy?
A ciliopathy is a disorder caused by dysfunction of primary cilia, cellular structures that sense environmental signals. Because cilia are present on many cell types, ciliopathies often affect multiple organ systems, including the skeleton, brain, kidneys, and eyes, producing diverse clinical features.
Why is CEP120 included on multiple NHS panels?
CEP120 variants cause a spectrum of overlapping conditions affecting skeletal development, brain structure, and other systems. Its inclusion on panels for skeletal dysplasias, ciliopathies, intellectual disability, and foetal anomalies ensures appropriate testing for patients presenting with any of these clinical features.