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CTC1
CST telomere replication complex component 1
The CTC1 gene provides instructions for a protein that is a key component of the CST complex, vital for maintaining telomere integrity at chromosome ends. The CTC1 gene encodes a protein integral to the CST complex, which plays a crucial role in protecting and replicating telomeres.
CTC1 is located on the short (p) arm of chromosome 17, at band 17p13.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The CTC1 gene, also known as CST telomere replication complex component 1, encodes a protein fundamental to the CST complex. Telomeres are short, repetitive DNA sequences located at chromosome termini. These structures prevent chromosomes from sticking together improperly or breaking down. As cells undergo division, telomeres in most cell types progressively shorten. When telomeres reach a critically reduced length, cells typically cease dividing or enter programmed cell death. The CST complex, of which the CTC1 protein is a critical member, participates in the specialised cellular machinery some cells deploy to replicate telomeres, preventing excessive shortening during division. Proper telomere maintenance supports normal cell division and chromosome stability.
What the gene does
CTC1 encodes a protein that operates as part of the CST complex, a group essential for telomere biology. Chromosome ends require protective structures to prevent DNA damage and preserve genomic integrity. The CST complex participates in replicating these terminal regions, ensuring they do not become excessively abbreviated as cells proliferate. Evidence suggests the CTC1 protein may additionally participate in DNA replication activities distinct from its telomere-related work, though these putative roles remain incompletely characterised.
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Chromosome location
The CTC1 gene is located on chromosome 17 at position 17p13.1. This means it resides on the short (p) arm of chromosome 17, within region 13, band 1. The gene provides the genetic blueprint for a protein consisting of 1217 amino acids.
Protein structure
The CTC1 protein is 1217 amino acids in length. Its structure includes a disordered region spanning amino acids 328-347. This flexible segment may facilitate interactions with various binding partners, a common feature for proteins involved in complex cellular processes such as DNA metabolism.
Key variants
Variants within the CTC1 gene can alter the protein's structure or function, potentially impairing its role in telomere maintenance. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions. Such alterations can disrupt the normal functioning of the CST complex, leading to impaired telomere protection and replication.
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.1190dup | p.Gly398fs | Pathogenic/Likely pathogenic | ★★☆☆ | Dyskeratosis congenita |
c.1360del | p.Glu454fs | Pathogenic/Likely pathogenic | ★★☆☆ | CTC1-related disorder |
c.150G>A | p.Trp50Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.1617+5G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Dyskeratosis congenita |
c.1668_1671del | p.Glu557fs | Pathogenic/Likely pathogenic | ★★☆☆ | Dyskeratosis congenita |
c.1683dup | p.Lys562Ter | Pathogenic/Likely pathogenic | ★★☆☆ | CTC1-related disorder |
c.1746del | p.Ser583fs | Pathogenic/Likely pathogenic | ★★☆☆ | CTC1-related disorder |
c.1753C>T | p.Gln585Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Dyskeratosis congenita |
c.1785_1786del | p.Cys596fs | Pathogenic/Likely pathogenic | ★★☆☆ | CTC1-related dyskeratosis congenita |
c.2176del | p.His726fs | Pathogenic/Likely pathogenic | ★★☆☆ | Cerebroretinal microangiopathy with calcifications and cysts 1 |
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 CTC1 gene are associated with inherited conditions, most notably Coats plus syndrome. At least 20 pathogenic variants in the CTC1 gene have been identified in individuals with Coats plus syndrome. This condition is characterised by an eye disorder called Coats disease, alongside abnormalities affecting the brain, bones, and gastrointestinal system. The CTC1 gene follows an autosomal recessive inheritance pattern, meaning an individual must inherit two copies of a pathogenic variant (one from each parent) to develop the condition. Additionally, the CTC1 gene has been linked to dyskeratosis congenita.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic CTC1 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
The CTC1 gene is included in several NHS Genomic Medicine Service (GMS) approved panels, indicating its clinical relevance in the UK. It appears on panels such as Haematological malignancies cancer susceptibility and Foetal anomalies (R21). It is also listed on panels for Cytopenia - NOT Fanconi anaemia (R91), Cytopenias and congenital anaemias, DDG2P, Intracerebral calcification disorders, Pulmonary Fibrosis, Familial (R421), Retinal disorders (R32), White matter disorders and cerebral calcification - childhood onset, and COVID-19 research.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the CTC1 gene?
The CTC1 gene provides instructions for making a protein that is a critical component of the CST complex. This complex is essential for maintaining telomeres, which are protective caps at the ends of chromosomes, safeguarding them from damage and ensuring proper replication.
What is Coats plus syndrome?
Coats plus syndrome is an inherited disorder linked to pathogenic variants in the CTC1 gene. It involves an eye condition called Coats disease, along with other abnormalities affecting multiple body systems such as the brain, bones, and gastrointestinal tract.
How does CTC1 relate to telomeres?
The CTC1 protein is part of the CST complex, which is responsible for protecting telomeres and helping to replicate them. This process ensures that telomeres do not become too short during cell division, which is crucial for preventing genomic instability.
References
- Gu P, Chang S. Functional characterization of human CTC1 mutations reveals novel mechanisms responsible for the pathogenesis of the telomere disease Coats plus. Aging cell. 2013. PMID: 23869908
- Chen LY, Majerská J, Lingner J. Molecular basis of telomere syndrome caused by CTC1 mutations. Genes & development. 2013. PMID: 24115768
- Anderson BH, Kasher PR, Mayer J. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nature genetics. 2012. PMID: 22267198
- Polvi A, Linnankivi T, Kivelä T. Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts. American journal of human genetics. 2012. PMID: 22387016
- Surovtseva YV, Churikov D, Boltz KA. Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes. Molecular cell. 2009. PMID: 19854131