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DDX11
DEAD/H-box helicase 11
The DDX11 gene provides instructions for the ChlR1 helicase enzyme, which is crucial for DNA replication, repair, and maintaining the stability of a cell's genetic information. The DDX11 gene encodes the ChlR1 protein, a type of helicase that unwinds DNA during cell division.
DDX11 is located on the short (p) arm of chromosome 12, at band 12p11.21. Arm ratio per GRCh38 - banding schematic.
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Overview
The DDX11 gene, also known as DEAD/H-box helicase 11, produces an enzyme called ChlR1. This enzyme is a helicase, meaning it binds to DNA and temporarily unwinds its double-stranded structure. This unwinding is necessary for fundamental cellular processes such as DNA replication and repair.
ChlR1's functions are critical for maintaining the stability of a cell's genetic material. It helps ensure that DNA is copied accurately before cell division and assists in correcting any errors that occur during this process. Additionally, it plays a role in the proper separation of chromosomes during cell division, contributing to healthy cellular function.
What the gene does
The ChlR1 enzyme, encoded by the DDX11 gene, acts as a helicase. Helicases are a class of enzymes that utilise energy from ATP hydrolysis to separate nucleic acid strands. In the context of DDX11, ChlR1 binds to DNA and unwinds its double helix, a crucial step before DNA can be copied during cell division.
Beyond DNA replication, ChlR1 is involved in repairing mistakes made when DNA is copied, contributing to the overall fidelity of the genetic code. It also has a role in managing sister chromatids, which are identical DNA copies formed after replication. ChlR1 helps keep these chromatids together until they are ready to separate into new cells during cell division. This multifaceted role in DNA handling and chromosome management highlights its importance in maintaining genomic stability.
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Chromosome location
The DDX11 gene is located on the short arm of chromosome 12 at position 11.21, denoted as 12p11.21. This specific address on the human genome helps researchers and clinicians identify its precise genomic context.
Protein structure
The DDX11 protein, ChlR1, is composed of 970 amino acids. Key functional regions within the protein include a Helicase ATP-binding domain, spanning amino acids 9-445, which is essential for its helicase activity. A DEAH box motif is situated within this domain, from amino acids 393-396, characteristic of a subfamily of helicases. Additionally, the protein contains two disordered regions: one from amino acids 289-312 and another from amino acids 818-849, which may play roles in protein interactions or flexibility.
Key variants
Genetic variants in the DDX11 gene can alter the function of the ChlR1 enzyme. These changes can range from single nucleotide alterations to larger deletions or insertions within the gene sequence. Depending on their nature and location, variants can lead to a reduction or complete loss of ChlR1 enzyme activity, impacting its crucial roles in DNA replication, repair, and chromosome stability.
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.1403dup | p.Ser469fs | Pathogenic/Likely pathogenic | ★★☆☆ | Warsaw breakage syndrome |
c.1591C>T | p.Gln531Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Warsaw breakage syndrome |
c.1672C>T | p.Arg558Ter | Pathogenic/Likely pathogenic | ★★☆☆ | DDX11-related disorders |
c.1763-1G>C | - | Pathogenic | ★★☆☆ | DDX11-related disorders |
c.1947T>A | p.Cys649Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Warsaw breakage syndrome |
c.1949-1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Warsaw breakage syndrome |
c.2230C>T | p.Gln744Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Warsaw breakage syndrome |
c.223C>T | p.Arg75Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.788G>A | p.Arg263Gln | Pathogenic/Likely pathogenic | ★★☆☆ | Warsaw breakage syndrome |
g.31087936AG[1] | - | 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 DDX11 gene are associated with inherited conditions. These conditions typically arise when variants severely impair or eliminate the function of the ChlR1 enzyme. The resulting cellular dysfunction, particularly in DNA handling and chromosome segregation, contributes to the specific symptoms observed in affected individuals.
No disease links recorded for this gene in our reference set.
UK clinical status
The DDX11 gene is recognised within the UK's NHS Genomic Medicine Service pathways. It is listed as 'green' on PanelApp for DDG2P, Foetal anomalies (R21), Intellectual disability, and Severe microcephaly (R88). This indicates there is sufficient evidence for its association with these conditions to be considered clinically actionable within NHS genomic testing.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the DDX11 gene?
The DDX11 gene provides instructions for making the ChlR1 enzyme, which is a helicase. This enzyme unwinds DNA strands to facilitate replication and repair, and it also helps maintain chromosome stability during cell division.
What happens if the DDX11 gene doesn't work correctly?
If the DDX11 gene does not function correctly, the ChlR1 enzyme's activity can be severely reduced or eliminated. This can lead to issues with DNA replication, repair, and proper chromosome separation, contributing to various health conditions.
How does DDX11 contribute to DNA stability?
DDX11 contributes to DNA stability by ensuring accurate DNA replication and repairing errors that occur during this process. It also helps in the proper segregation of sister chromatids during cell division, preventing genomic instability.
References
- Capo-Chichi JM, Bharti SK, Sommers JA. Identification and biochemical characterization of a novel mutation in DDX11 causing Warsaw breakage syndrome. Human mutation. 2013. PMID: 23033317
- Shah N, Inoue A, Woo Lee S. Roles of ChlR1 DNA helicase in replication recovery from DNA damage. Experimental cell research. 2013. PMID: 23797032
- Inoue A, Hyle J, Lechner MS. Mammalian ChlR1 has a role in heterochromatin organization. Experimental cell research. 2011. PMID: 21854770
- van der Lelij P, Chrzanowska KH, Godthelp BC. Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11/ChlR1. American journal of human genetics. 2010. PMID: 20137776