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CWC27
CWC27 spliceosome associated cyclophilin
The CWC27 gene provides instructions for making a protein involved in the spliceosome, a complex molecular machine essential for processing RNA inside cells. The CWC27 gene is crucial for normal cellular function, specifically in the process of RNA splicing.
CWC27 is located on the long (q) arm of chromosome 5, at band 5q12.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The CWC27 gene, also known as CWC27 spliceosome associated cyclophilin, provides the genetic blueprint for a protein integral to the spliceosome. This cellular machinery is responsible for precisely removing non-coding regions (introns) from messenger RNA (mRNA) precursors, a vital step before proteins can be synthesised. Proper functioning of the CWC27 protein supports accurate gene expression across many bodily systems.
Pathogenic variants in the CWC27 gene are linked to rare inherited conditions, often presenting with a spectrum of developmental abnormalities. Understanding the CWC27 gene helps to clarify the underlying mechanisms of these conditions.
What the gene does
The protein encoded by the CWC27 gene is a component of the spliceosome, a large and dynamic molecular complex found within the nucleus of eukaryotic cells. The spliceosome carries out messenger RNA (mRNA) splicing, a critical process where immature RNA transcripts are processed. During splicing, non-coding sequences called introns are precisely excised, and the remaining coding sequences, known as exons, are joined together to form mature mRNA.
The CWC27 protein’s role ensures the accurate assembly and function of the spliceosome. Its activity is necessary for the production of functional mature mRNA, which subsequently directs protein synthesis. Errors in this intricate splicing process, potentially due to CWC27 dysfunction, can lead to the production of faulty proteins or insufficient amounts of essential proteins, impacting normal cellular processes and development.
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Chromosome location
The CWC27 gene is situated on chromosome 5, specifically at position 5q12.3. Chromosome 5 is one of the 23 pairs of chromosomes in humans, with 'q' denoting the long arm of the chromosome. The precise location 5q12.3 helps to pinpoint the gene's position within the vast human genome.
Protein structure
The CWC27 protein consists of 472 amino acids. Its structural organisation includes several notable regions and domains. From amino acids 11 to 166, it contains a PPIase cyclophilin-type domain, which is typically involved in protein folding and chaperone activity. Additionally, the protein features two distinct disordered regions: one spanning amino acids 206-386 and another from amino acids 398-472. Within the first disordered region, there are two coiled-coil motifs: one from amino acids 206-230 and a second from amino acids 306-377. These coiled-coil structures often mediate protein-protein interactions.
Key variants
Genetic variations, or variants, in the CWC27 gene can alter the protein's structure or function, impacting its role in the spliceosome. These changes range from single base-pair substitutions to larger deletions or insertions within the gene sequence. Depending on their nature and location, CWC27 variants may be classified as benign, likely benign, uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants are those conclusively linked 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.1002del | p.Lys334_Val335insTer | Pathogenic/Likely pathogenic | ★★☆☆ | CWC27-related disorder |
c.1002dup | p.Val335fs | Pathogenic | ★★☆☆ | Metaphyseal chondrodysplasia-retinitis pigmentosa syndrome |
c.1066_1070del | p.Ala356fs | Pathogenic | ★★☆☆ | Metaphyseal chondrodysplasia-retinitis pigmentosa syndrome |
c.1101T>G | p.Tyr367Ter | Pathogenic/Likely pathogenic | ★★☆☆ | CWC27-related disorder |
c.1120C>T | p.Gln374Ter | Pathogenic/Likely pathogenic | ★★☆☆ | CWC27-related disorder |
c.1156dup | p.Leu386fs | Pathogenic | ★★☆☆ | CWC27-related disorder |
c.326del | p.Asn109fs | Pathogenic/Likely pathogenic | ★★☆☆ | CWC27-related disorder |
c.427C>T | p.Arg143Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Metaphyseal chondrodysplasia-retinitis pigmentosa syndrome |
c.495G>A | p.Glu165= | Pathogenic | ★★☆☆ | Retinitis pigmentosa |
c.666_669del | p.Ser222fs | Pathogenic | ★★☆☆ | not provided |
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
Pathogenic variants in the CWC27 gene are associated with various rare developmental conditions. The clinical presentation linked to CWC27 variants can be diverse, often involving complex developmental and neurological challenges. These conditions are typically inherited, highlighting the gene's critical role in early development and proper central nervous system function. Specific conditions are further detailed on the condition-specific pages.
No disease links recorded for this gene in our reference set.
UK clinical status
In the UK, the CWC27 gene is recognised on several NHS Genomic Medicine Service national test panels within PanelApp, indicating its clinical significance. It is listed with a 'green' status on the DDG2P panel, the Foetal anomalies panel (R21), the Intellectual disability panel (R29), and the Retinal disorders panel (R32). This green status signifies that there is sufficient evidence to support its role in related disorders and it is actively considered in diagnostic testing for these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the CWC27 gene?
The CWC27 gene instructs the production of a protein that is a crucial part of the spliceosome. This molecular machine is responsible for RNA splicing, where non-coding sections are removed from RNA to create functional messenger RNA for protein synthesis.
What happens if there are variants in the CWC27 gene?
Variants in the CWC27 gene can disrupt the normal function of the protein, leading to errors in RNA splicing. This can result in faulty or insufficient protein production, which is associated with various rare developmental and neurological conditions.
How is the CWC27 gene status determined in the UK?
In the UK, the clinical relevance of the CWC27 gene is recognised through its inclusion on several NHS Genomic Medicine Service national test panels, such as those for DDG2P, Foetal anomalies, Intellectual disability, and Retinal disorders. These panels assess genes for their association with specific conditions.