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C2CD3
C2 domain containing 3 centriole elongation regulator
The C2CD3 gene provides instructions for a protein crucial for centriole elongation, a fundamental process in cell division and the formation of cellular structures like cilia. The C2CD3 gene is essential for proper cellular architecture and function, particularly in forming centrioles and cilia.
C2CD3 is located on the long (q) arm of chromosome 11, at band 11q13.4. Arm ratio per GRCh38 - banding schematic.
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Overview
The C2CD3 gene, also known as C2 domain containing 3 centriole elongation regulator, is a key component in cellular organisation. Its protein product plays a critical role in the biogenesis of centrioles, which are cylindrical structures involved in cell division and the formation of cilia and flagella. Errors in this gene can lead to a range of developmental abnormalities due to impaired cellular processes.
The C2CD3 gene is classified in carrier screening panels for autosomal recessive and autosomal dominant inheritance patterns, indicating that individuals may carry one altered copy without symptoms, but two altered copies, or a single dominant change, can lead to conditions.
What the gene does
The C2CD3 protein is fundamentally involved in centriole elongation, a process vital for the formation of mature centrioles. Centrioles are part of the centrosome, which organises microtubules during cell division and acts as the basal body for cilia. Therefore, C2CD3's function is intimately linked to cell division, cell motility, and signalling pathways that depend on properly formed cilia.
Its specific role in elongation suggests it acts as a scaffold or a regulator, facilitating the addition of key components required to extend the centriole structure. Disruptions in C2CD3 function can lead to defective centrioles, which in turn can impair cell division and ciliary function, contributing to a diverse group of conditions known as ciliopathies.
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Chromosome location
The C2CD3 gene is situated on chromosome 11, specifically at position 11q13.4. This location refers to the long arm (q) of chromosome 11, within region 13 and sub-band 4. The precise genomic coordinates help researchers link specific genetic variants to their physical location on the chromosome.
Protein structure
The C2CD3 protein is quite large, comprising 2353 amino acids. Its structure includes multiple C2 domains, which are typically involved in calcium-dependent phospholipid binding and signal transduction. Specifically, the protein contains six C2 domains: C2 1 (amino acids 521-678), C2 2 (amino acids 787-919), C2 3 (amino acids 985-1147), C2 4 (amino acids 1171-1339), C2 5 (amino acids 1403-1533), and C2 6 (amino acids 1617-1745). Additionally, several disordered regions are present, including those at amino acids 1-27, 488-508, 549-568, 1569-1591, 1822-1846, 1972-2032, 2084-2118, 2130-2269, and 2301-2334. These disordered regions may provide flexibility and participate in protein-protein interactions.
Key variants
Variants within the C2CD3 gene can alter the function or production of the C2CD3 protein, potentially affecting centriole elongation and ciliary development. These genetic changes can range from single nucleotide differences to larger deletions or insertions within the gene sequence. Depending on their nature and location, variants may lead to a reduced amount of functional protein or a completely non-functional protein, disrupting vital cellular processes.
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.1861C>T | p.Arg621Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Orofaciodigital syndrome type 14 |
c.1996C>T | p.Arg666Ter | Pathogenic | ★★☆☆ | Orofaciodigital syndrome type 14 |
c.2302C>T | p.Arg768Ter | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.2706_2710dup | p.His904fs | Pathogenic/Likely pathogenic | ★★☆☆ | Orofaciodigital syndrome type 14 |
c.2733_2740delAGATGCTA | p.Ala913fs | Pathogenic/Likely pathogenic | ★★☆☆ | Orofaciodigital syndrome type 14 |
c.2969_2972delinsGGTTTACA | p.Ser990fs | Pathogenic/Likely pathogenic | ★★☆☆ | Orofaciodigital syndrome type 14 |
c.3911-2A>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Fetal anomalies with a likely genetic cause |
c.994dup | p.Val332fs | Pathogenic/Likely pathogenic | ★★☆☆ | Orofaciodigital syndrome type 14 |
c.1534C>T | p.Gln512Ter | Pathogenic | ★☆☆☆ | not provided |
c.3160+1G>A | - | Pathogenic | ★☆☆☆ | Fetal anomalies with a likely genetic cause |
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
Variants in the C2CD3 gene are associated with a spectrum of inherited conditions, frequently categorised as ciliopathies. These disorders arise from defects in cilia, which are critical for various cellular functions and organ development. The clinical manifestations can be wide-ranging, affecting multiple organ systems such as the skeletal system, brain, and kidneys. The severity and specific symptoms depend on the particular genetic variant and its impact on protein function.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic C2CD3 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
The C2CD3 gene is included in several NHS England Genomic Medicine Service national test panels. It is listed as 'green' for Clefting, DDG2P, Foetal anomalies (R21), Intellectual disability (R29), Neurological ciliopathies, Rare multisystem ciliopathy disorders, Skeletal ciliopathies, and Skeletal dysplasia (R104). This indicates that variants in C2CD3 are considered to have a strong evidence base for causing these conditions and are routinely assessed in a diagnostic setting.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the C2CD3 gene?
The C2CD3 gene provides instructions for a protein that is essential for centriole elongation, a process critical for proper cell division and the formation of cilia, which are tiny hair-like structures on cells.
How does C2CD3 relate to cilia?
C2CD3 is crucial for forming proper centrioles, which then act as basal bodies for cilia. Defects in C2CD3 can therefore lead to dysfunctional cilia, resulting in a group of disorders known as ciliopathies.
Is the C2CD3 gene associated with any specific health conditions?
Yes, variants in the C2CD3 gene are associated with a range of inherited conditions, particularly developmental disorders and ciliopathies that can affect various organ systems.