On this page
DNAI1
dynein axonemal intermediate chain 1
The DNAI1 gene provides instructions for making an intermediate chain protein essential for the proper function of cilia, which are microscopic, hair-like structures involved in cellular movement. The DNAI1 gene is vital for producing a component of the dynein protein complex, specifically the intermediate chain 1.
DNAI1 is located on the short (p) arm of chromosome 9, at band 9p13.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 9 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The DNAI1 gene, short for dynein axonemal intermediate chain 1, plays a critical role in the proper functioning of cilia. Cilia are microscopic, finger-like projections found on the surface of many cells in the human body, where they facilitate movement of cells or surrounding fluids. The protein produced by DNAI1 is a key component of the machinery that enables this ciliary movement.
What the gene does
The DNAI1 gene encodes intermediate chain 1, a subunit of the dynein protein complex. Dynein complexes are molecular motors responsible for generating the force required for cilia to move. Within the core structure of cilia, known as the axoneme, dynein complexes are organised into inner dynein arms (IDAs) and outer dynein arms (ODAs). The DNAI1 protein is specifically found within the outer dynein arms, where it contributes to the coordinated bending motion of the axoneme. This precise movement is crucial for various biological processes, including clearing mucus from the airways and guiding cell migration during development.
Video: Genetics 101
Chromosome location
The DNAI1 gene is located on chromosome 9 at position 9p13.3. This genomic address specifies its exact site on the short arm of chromosome 9, providing its location within the human genome.
Protein structure
The DNAI1 protein is 699 amino acids long. It features several distinct regions, including two disordered regions: one at amino acids 1-54 and another at amino acids 140-170. The protein also contains seven WD repeats, which are common protein-protein interaction motifs. These include WD 1 (amino acids 320-370), WD 2 (amino acids 375-413), WD 3 (amino acids 422-465), WD 4 (amino acids 474-526), WD 5 (amino acids 531-570), WD 6 (amino acids 574-612), and WD 7 (amino acids 618-658).
Key variants
Variants within the DNAI1 gene can affect the structure and function of the intermediate chain 1 protein, thereby impairing ciliary movement. These genetic changes can range from small alterations to larger deletions or insertions, potentially leading to a non-functional or improperly functioning protein. Identifying specific variants is important for understanding the genetic basis of 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.1011_1012dup | p.Leu338fs | Pathogenic/Likely pathogenic | ★★☆☆ | Kartagener syndrome |
c.1319G>A | p.Trp440Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Kartagener syndrome |
c.139del | p.Ala47fs | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.1431del | p.Lys477fs | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.1533del | p.Met511fs | Pathogenic | ★★☆☆ | Kartagener syndrome |
c.155del | p.Pro52fs | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.1643G>A | p.Trp548Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Kartagener syndrome |
c.1644del | p.Ser547_Trp548insTer | Pathogenic | ★★☆☆ | Kartagener syndrome |
c.1653C>G | p.Tyr551Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
c.1704G>A | p.Trp568Ter | 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
Pathogenic variants in the DNAI1 gene are primarily associated with inherited conditions that affect ciliary function. The most notable of these is Primary Ciliary Dyskinesia, an autosomal recessive disorder characterised by impaired ciliary motility. Additionally, DNAI1 variants have been linked to Heterotaxy syndrome, which involves abnormal left-right body axis development, often due to dysfunctional cilia during embryonic development.
- Primary ciliary dyskinesia Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic DNAI1 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 DNAI1 gene is included in several NHS Genomic Medicine Service national test panels. It is listed as 'green' for Foetal anomalies (R21), Laterality disorders and isomerism (R139), Primary ciliary disorders, and Respiratory ciliopathies including non-CF bronchiectasis (R189), indicating its recognised clinical utility in these areas within the UK healthcare system.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the DNAI1 gene?
The DNAI1 gene provides instructions for making an intermediate chain protein that is a crucial part of the dynein complex, which generates the force needed for the movement of cilia, microscopic hair-like structures on cells.
What conditions are associated with DNAI1 gene variants?
Variants in the DNAI1 gene are primarily associated with Primary Ciliary Dyskinesia, an inherited condition causing impaired ciliary movement. They can also be linked to Heterotaxy syndrome, a disorder of abnormal organ arrangement.
How is DNAI1 involved in ciliary movement?
The protein produced by DNAI1 is a component of the outer dynein arms within cilia. These arms are molecular motors that facilitate the coordinated bending of the ciliary structure, which is essential for effective ciliary motion.
References
- Ziętkiewicz E, Nitka B, Voelkel K. Population specificity of the DNAI1 gene mutation spectrum in primary ciliary dyskinesia (PCD). Respiratory research. 2010. PMID: 21143860
- Escudier E, Duquesnoy P, Papon JF. Ciliary defects and genetics of primary ciliary dyskinesia. Paediatric respiratory reviews. 2009. PMID: 19410201
- Leigh MW, Pittman JE, Carson JL. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genetics in medicine : official journal of the American College of Medical Genetics. 2009. PMID: 19606528
- Failly M, Saitta A, Muñoz A. DNAI1 mutations explain only 2% of primary ciliary dykinesia. Respiration; international review of thoracic diseases. 2008. PMID: 18434704
- Zariwala MA, Leigh MW, Ceppa F. Mutations of DNAI1 in primary ciliary dyskinesia: evidence of founder effect in a common mutation. American journal of respiratory and critical care medicine. 2006. PMID: 16858015
- Pennarun G, Escudier E, Chapelin C. Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. American journal of human genetics. 1999. PMID: 10577904
- Adam MP, Bick S, Mirzaa GM. Primary Ciliary Dyskinesia. 1993. PMID: 20301301