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DNAH11
dynein axonemal heavy chain 11
The DNAH11 gene provides instructions for producing dynein axonemal heavy chain 11, a protein essential for the proper movement of cilia, which are microscopic, hair-like cellular structures. DNAH11 plays a critical role in the function of cilia, which are vital for processes such as clearing airways and facilitating cell movement.
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, also known as dynein axonemal heavy chain 11, is integral to the proper functioning of cilia. Cilia are tiny, finger-like projections found on the surface of many cell types, including those lining the respiratory and reproductive systems. These structures perform coordinated, sweeping movements that are essential for various physiological processes, such as clearing mucus from the airways and moving fluids across cell surfaces. The protein encoded by DNAH11 is a key component of the machinery that powers ciliary motion.
What the gene does
The DNAH11 gene directs the synthesis of the dynein axonemal heavy chain 11 protein, which is part of the dynein protein complex. This complex is crucial for the function of cilia, which are microscopic, hair-like extensions from cells. Within the core of cilia, known as the axoneme, dynein forms structures called inner dynein arms (IDAs) and outer dynein arms (ODAs). These arms generate the mechanical force required for cilia to bend and move in a coordinated manner. Specifically, the DNAH11 protein is a heavy chain component found within the outer dynein arms, contributing to the overall force production necessary for effective ciliary beating. The collective movement of these dynein arms drives the back-and-forth motion of the entire cilium, enabling it to move cells or the surrounding fluid.
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Chromosome location
The DNAH11 gene is situated on the short arm of chromosome 7, specifically at position 7p15.3. This precise genomic location helps in identifying and studying the gene within the human genome.
Protein structure
The DNAH11 protein is a large protein, composed of 4516 amino acids. Its structure includes several distinct regions and coiled-coil domains. The N-terminal region comprises a Stem from amino acids 1-1854, which contains a Coiled coil domain between amino acids 1274-1327. Following this are six AAA (ATPase Associated with various cellular Activities) domains: 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). A Stalk region is present from amino acids 3072-3403, featuring two Coiled coil domains (amino acids 3072-3136 and 3312-3403). Another Coiled coil domain is located between amino acids 3668-3703.
Key variants
Genetic variations within the DNAH11 gene can impact the structure and function of the dynein axonemal heavy chain 11 protein. These variants, also known as mutations, can lead to the production of a non-functional or reduced amount of the protein. The consequence is often impaired ciliary movement, which underpins the symptoms observed in associated 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 | ★★☆☆ | Respiratory ciliopathies including non-CF bronchiectasis |
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.793_794insCAGCT | p.Arg265fs | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.927_931del | p.Ser312fs | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.3989G>A | p.Trp1330Ter | Pathogenic | ★☆☆☆ | Primary ciliary dyskinesia |
c.4628G>A | p.Trp1543Ter | Pathogenic | ★☆☆☆ | Primary ciliary dyskinesia |
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 primarily associated with primary ciliary dyskinesia (PCD), a condition characterised by impaired ciliary function. Individuals with PCD often experience recurrent respiratory tract infections due to ineffective mucus clearance, as well as fertility issues. In some cases, DNAH11 variants are also implicated in heterotaxy syndrome, which involves abnormal placement 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 panels within the UK's NHS Genomic Medicine Service, as listed in PanelApp. It is rated 'green' for its role in Foetal anomalies (R21), Laterality disorders and isomerism (R139), Primary ciliary disorders, and Respiratory ciliopathies including non-CF bronchiectasis (R189), indicating strong evidence for its involvement in these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What are cilia and why are they important?
Cilia are microscopic, hair-like projections extending from the surface of cells. They are crucial for moving substances across cell surfaces, such as clearing mucus from the lungs or moving eggs in the fallopian tubes, and their proper function is vital for respiratory health and fertility.
What is primary ciliary dyskinesia (PCD)?
Primary ciliary dyskinesia is a genetic disorder characterised by defects in the structure and function of cilia. This leads to impaired ciliary movement, resulting in chronic respiratory infections, fertility problems, and sometimes the misplacement of internal organs.
How does the DNAH11 gene relate to male and female fertility?
In both males and females, properly functioning cilia are important for fertility. In males, cilia on sperm are essential for motility, and in females, cilia lining the fallopian tubes help transport eggs. Impaired ciliary function due to DNAH11 variants can therefore contribute to reduced fertility in both sexes.
References
- Adam MP, Bick S, Mirzaa GM. Primary Ciliary Dyskinesia. 1993. PMID: 20301301