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DNAH11
dynein axonemal heavy chain 11
The DNAH11 gene provides instructions for making a protein component of dynein, essential for the proper movement of cilia in various bodily systems. The DNAH11 gene codes for the dynein axonemal heavy chain 11 protein, which is a crucial part of outer dynein arms in cilia.
DNAH11 is located on the short (p) arm of chromosome 7, at band 7p15.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The DNAH11 gene is responsible for producing the dynein axonemal heavy chain 11 protein. This protein is a critical structural component of cilia, which are small, finger-like projections found on the surface of many cells throughout the body.
Cilia play vital roles in various physiological processes, including clearing mucus from the respiratory tract, moving fluid in the brain, and facilitating the movement of reproductive cells. Proper function of the DNAH11 protein is necessary for the coordinated, wave-like motion of cilia.
What the gene does
The protein encoded by the DNAH11 gene is a heavy chain subunit of dynein, a large protein complex involved in generating force for ciliary movement. Specifically, this heavy chain protein is found within the outer dynein arms (ODAs) of the axoneme, the core structure of cilia. Within the axoneme, dynein complexes facilitate the bending motion required for cilia to move efficiently.
This coordinated movement is crucial for various biological functions, such as the clearance of foreign particles and mucus from the respiratory system, and is also important for fertility. Impaired DNAH11 protein function can lead to dysregulated ciliary motion, affecting these physiological processes.
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Chromosome location
The DNAH11 gene is located on chromosome 7, specifically at position 7p15.3. This genomic address specifies the precise location of the gene within the human genome.
Protein structure
The DNAH11 protein is a large molecule consisting of 4516 amino acids. Its intricate structure includes several distinct regions and coiled-coil domains. Key regions include the Stem (amino acids 1-1854) and Stalk (amino acids 3072-3403). The protein also contains multiple AAA domains, specifically AAA 1 (amino acids 1855-2076), AAA 2 (amino acids 2136-2366), AAA 3 (amino acids 2472-2719), AAA 4 (amino acids 2817-3066), AAA 5 (amino acids 3459-3686), and AAA 6 (amino acids 3896-4122). Several coiled-coil domains are interspersed throughout the protein, located at amino acids 1274-1327, 3072-3136, 3312-3403, and 3668-3703.
Key variants
Genetic variations, or changes, within the DNAH11 gene can impact the production or function of the dynein axonemal heavy chain 11 protein. These variants can lead to a reduction in the amount of functional protein produced, or result in a protein with altered structure that cannot perform its role effectively. Such changes can disrupt the normal movement of cilia and contribute to various health conditions.
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.10896+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.12970C>T | p.Gln4324Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.2709del | p.Trp904fs | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia 7 |
c.4095+1G>A | A1366T | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.4658C>G | p.Ser1553Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.4669C>T | p.Arg1557Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia 7 |
c.5220_5238del | p.Gln1740fs | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.6547-963G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia 7 |
c.793_794insCAGCT | p.Arg265fs | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.8632C>T | p.Gln2878Ter | Pathogenic/Likely pathogenic | ★★☆☆ | DNAH11-related disorders |
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 DNAH11 gene are associated with inherited conditions primarily affecting ciliary function. These include primary ciliary dyskinesia, which is characterised by recurrent respiratory tract infections, situs abnormalities (abnormally placed internal organs), and reduced fertility. The gene is also linked to heterotaxy syndrome, a condition involving abnormal arrangement of internal organs.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic DNAH11 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 DNAH11 gene is included in several UK NHS national genomic testing panels. It is listed on the Foetal anomalies (R21) panel, the Laterality disorders and isomerism (R139) panel, and the Primary ciliary disorders and Respiratory ciliopathies including non-CF bronchiectasis (R189) panels, all with a 'green' status indicating their clinical utility.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the DNAH11 gene?
The DNAH11 gene provides instructions for making a heavy chain protein that is a vital component of dynein. Dynein is a complex that generates the force needed for the coordinated movement of cilia, which are microscopic, hair-like structures found on cell surfaces.
What happens if the DNAH11 gene doesn't work correctly?
If the DNAH11 gene has variants, it can lead to the production of non-functional or insufficient amounts of the DNAH11 protein. This can impair ciliary movement, contributing to conditions like primary ciliary dyskinesia, characterised by respiratory issues, laterality defects, and fertility problems.
Is DNAH11 associated with any specific medical conditions?
Yes, variants in the DNAH11 gene are known to cause primary ciliary dyskinesia (PCD), a genetic disorder affecting cilia. It is also associated with heterotaxy syndrome, which involves abnormal positioning of internal organs.
References
- Adam MP, Bick S, Mirzaa GM. Primary Ciliary Dyskinesia. 1993. PMID: 20301301