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CEP41
centrosomal protein 41
CEP41 is located on the long (q) arm of chromosome 7, at band 7q32.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The CEP41 gene encodes centrosomal protein 41, a component of the centrosome that is essential for the formation and function of primary cilia. These microscopic structures extend from the cell surface and serve as signalling hubs during embryonic development and tissue maintenance. Primary cilia are particularly important in the developing brain, kidneys, eyes, and skeleton, coordinating signals that guide cell division, migration, and differentiation.
Pathogenic variants in CEP41 disrupt normal ciliary assembly and signalling, resulting in a spectrum of multisystem disorders collectively termed ciliopathies. These conditions typically affect neurological development, kidney structure, and retinal function. The gene was first linked to human disease through studies of families with Joubert syndrome, a rare neurological condition characterised by distinctive brain malformations and developmental delay.
What the gene does
The CEP41 protein localises to the centrosome, an organelle that serves as the primary microtubule-organising centre in animal cells. Within the centrosome, CEP41 participates in the assembly and stabilisation of primary cilia by regulating the transport of structural components to the ciliary base. Cilia themselves function as cellular antennae, housing signalling receptors that detect extracellular molecules and mechanical cues.
CEP41 appears to coordinate the trafficking of proteins required for ciliary structure maintenance and receptor localisation. Research suggests the protein contributes to the transition zone, a specialised region at the base of the cilium that acts as a gatekeeper controlling which molecules enter and exit the ciliary compartment. This quality-control function ensures that cilia maintain the correct composition of signalling proteins, which is critical for pathways including Hedgehog signalling and Wnt signalling during embryogenesis. When CEP41 function is compromised, cells produce shorter or malformed cilia that cannot properly transduce developmental signals, leading to the multiorgan manifestations observed in affected individuals.
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Chromosome location
CEP41 is located on the long arm of chromosome 7 at position 32.2, designated as 7q32.2. This chromosomal region contains a cluster of genes involved in various cellular processes. The precise genomic structure of CEP41, including exon count and intronic organisation, has not been extensively characterised in publicly available databases, though the gene produces a transcript encoding a 373-amino-acid protein.
Protein structure
The CEP41 protein comprises 373 amino acids with a modular domain organisation. The central portion contains a Rhodanese domain spanning amino acids 169 to 266, a structural fold typically associated with sulfur transfer reactions or, in some contexts, protein-protein interactions. Flanking this domain are two disordered regions: one extending from amino acids 89 to 137 and another from amino acids 275 to 373. Disordered regions in centrosomal proteins often provide flexibility for dynamic interactions with multiple binding partners during the cell cycle and ciliogenesis, allowing the protein to adapt to changing cellular contexts.
Key variants
Pathogenic variants in CEP41 follow autosomal recessive inheritance, meaning affected individuals typically inherit two altered copies of the gene, one from each parent. Reported variants include missense changes that alter single amino acids within the Rhodanese domain, as well as nonsense and frameshift variants predicted to result in truncated proteins. The distribution of pathogenic variants across the gene suggests that both complete loss of protein function and disruption of specific protein interactions can contribute to disease.
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.34-2A>G | - | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome 15 |
c.418C>T | p.Gln140Ter | Pathogenic | ★★☆☆ | Joubert syndrome 15 |
c.423-2A>C | - | Pathogenic | ★★☆☆ | Joubert syndrome 15 |
c.856C>T | p.Arg286Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.156del | p.Arg51_Tyr52insTer | Pathogenic | ★☆☆☆ | Joubert syndrome 15 |
c.162del | p.Asp55fs | Pathogenic | ★☆☆☆ | Inborn genetic diseases |
c.313_314dup | p.Thr106fs | Pathogenic | ★☆☆☆ | Joubert syndrome 15 |
c.542_545del | p.Arg181fs | Pathogenic | ★☆☆☆ | Joubert syndrome 15 |
c.55C>T | p.Gln19Ter | Pathogenic | ★☆☆☆ | Joubert syndrome 15 |
c.880del | p.Leu294fs | Pathogenic | ★☆☆☆ | Joubert syndrome 15 |
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
CEP41-related conditions belong to the ciliopathy spectrum, a group of disorders caused by defective cilia formation or function. The most commonly recognised presentation is Joubert syndrome, characterised by a distinctive brain malformation called the molar tooth sign visible on brain imaging, along with developmental delay, abnormal breathing patterns in infancy, and low muscle tone. Some affected individuals also develop kidney cysts, retinal degeneration leading to vision loss, or extra fingers or toes. The severity and combination of features can vary considerably between individuals, even within the same family, reflecting the complex role of cilia in coordinating multiple developmental processes across organ systems.
No disease links recorded for this gene in our reference set.
UK clinical status
CEP41 holds green classification status on multiple NHS Genomic Medicine Service gene panels, reflecting strong evidence for its role in inherited disease. The gene appears on panels including DDG2P, Fetal Anomalies, Intellectual Disability, Neurological Ciliopathies, Ophthalmological Ciliopathies, Rare Multisystem Ciliopathy Disorders, and Renal Ciliopathies. This broad panel representation underscores the multisystem nature of CEP41-related conditions and supports the inclusion of this gene in diagnostic testing for individuals presenting with features consistent with ciliopathies, particularly when neurological, renal, or retinal involvement is present.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What inheritance pattern do CEP41 variants follow?
CEP41-related conditions are inherited in an autosomal recessive pattern. This means an individual must inherit two pathogenic variants, one from each parent, to develop the condition. Parents who each carry one variant are typically unaffected but have a 25% chance with each pregnancy of having an affected child.
How do CEP41 variants affect cilia?
Pathogenic variants in CEP41 disrupt the protein's role in assembling and maintaining primary cilia, the cellular structures that detect environmental signals. When CEP41 function is compromised, cells produce abnormal or shortened cilia that cannot properly coordinate developmental signalling pathways, leading to the multiorgan features observed in ciliopathies.
Can CEP41 variants cause isolated developmental delay without other symptoms?
While developmental delay is a common feature of CEP41-related conditions, these disorders typically involve multiple organ systems. Most affected individuals have brain malformations, and many develop kidney, eye, or skeletal abnormalities. Comprehensive clinical evaluation is needed to identify the full spectrum of involvement in any individual.