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DNAL1
dynein axonemal light chain 1
DNAL1 is located on the long (q) arm of chromosome 14, at band 14q24.3. Arm ratio per GRCh38 - banding schematic.
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Overview
DNAL1 (dynein axonemal light chain 1) encodes a structural component of the outer dynein arm complex found in motile cilia and flagella. Cilia are microscopic, hair-like structures that project from the surface of many cell types, including those lining the respiratory tract, reproductive organs, and brain ventricles. The rhythmic beating of these cilia depends on dynein motor proteins that convert chemical energy into mechanical force.
Pathogenic variants in DNAL1 disrupt the assembly or function of the outer dynein arm, leading to abnormal ciliary motion. This results in impaired mucus clearance from the airways and compromised ciliary function in other organ systems. DNAL1-related conditions follow an autosomal recessive inheritance pattern, meaning that two altered copies of the gene are required for disease to manifest.
What the gene does
The DNAL1 protein functions as a light chain subunit within the outer dynein arm, a multi-protein complex anchored along the outer doublet microtubules of the ciliary axoneme. Dynein arms generate the sliding forces between adjacent microtubule doublets that produce the characteristic bending motion of cilia and flagella. Light chains such as DNAL1 contribute to the structural integrity of the dynein complex and may help regulate motor activity.
Within the respiratory epithelium, coordinated ciliary beating propels a layer of mucus upwards from the lungs, trapping inhaled particles and pathogens for removal. DNAL1 participates in this mucociliary clearance mechanism by ensuring proper dynein arm assembly and motor function. The protein also plays a role in other ciliated tissues, including the ependymal cells lining brain ventricles and the epithelial cells of the reproductive tract, where ciliary beating facilitates fluid movement and cellular transport.
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Chromosome location
DNAL1 is located on the long arm of chromosome 14 at cytogenetic band 14q24.3. The gene spans a relatively compact genomic region and encodes a 190-amino-acid protein. Chromosome 14 contains numerous genes involved in developmental processes and cellular signalling pathways.
Protein structure
The DNAL1 protein comprises 190 amino acids and contains a series of leucine-rich repeat (LRR) motifs that mediate protein-protein interactions. The structure includes LRR 1 (amino acids 49-70), LRR 2 (amino acids 71-92), LRR 3 (amino acids 94-115), and LRR 4 (amino acids 116-137), which form a characteristic curved solenoid architecture. These repeats are followed by an LRRCT domain (amino acids 150-190) that caps the C-terminal end of the repeat structure. This domain organisation facilitates the protein's incorporation into the larger dynein arm assembly and enables interactions with other dynein subunits.
Key variants
Pathogenic variants in DNAL1 typically result in loss of protein function, either through premature truncation, missense changes that destabilise the protein fold, or alterations affecting critical interaction surfaces. Because DNAL1 follows autosomal recessive inheritance, individuals carrying one pathogenic variant are typically unaffected carriers, whilst those with variants in both gene copies may develop ciliary dysfunction. Variants affecting the leucine-rich repeat domains can disrupt the protein's ability to integrate into the dynein complex.
Sample of pathogenic variants
8 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.224_230del | p.Ile74_Leu75insTer | Pathogenic/Likely pathogenic | ★★☆☆ | Primary ciliary dyskinesia |
g.(?_74153942)_(74156238_?)del | - | Pathogenic | ★☆☆☆ | Primary ciliary dyskinesia 16 |
g.(?_73671522)_(73671617_?)del | - | Pathogenic | ★☆☆☆ | Primary ciliary dyskinesia 16 |
c.23_24del | p.Lys8fs | Pathogenic | ★☆☆☆ | Primary ciliary dyskinesia |
c.296G>A | p.Trp99Ter | Pathogenic | ★☆☆☆ | Primary ciliary dyskinesia 16 |
c.384del | p.Asp129fs | Pathogenic | ★☆☆☆ | Primary ciliary dyskinesia 16 |
c.449A>G | p.Asn150Ser | Pathogenic | ★☆☆☆ | Primary ciliary dyskinesia 16 |
c.486G>A | p.Trp162Ter | Pathogenic | ★☆☆☆ | Primary ciliary dyskinesia 16 |
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
Biallelic pathogenic variants in DNAL1 are associated with primary ciliary dyskinesia, a genetically heterogeneous condition characterised by chronic respiratory infections, bronchiectasis, and sinusitis resulting from impaired mucociliary clearance. Some affected individuals may also experience laterality defects during embryonic development, as ciliary function contributes to establishing left-right body asymmetry. The severity and specific features can vary depending on the nature of the genetic variants and their impact on dynein arm assembly.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic DNAL1 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
DNAL1 is recognised on multiple UK NHS Genomic Medicine Service gene panels reflecting its role in ciliary biology. The gene holds green classification status on the Fetal anomalies panel (R21), the Primary ciliary disorders panel, and the Respiratory ciliopathies including non-CF bronchiectasis panel (R189). Green status indicates sufficient evidence to support clinical diagnostic use, and DNAL1 testing may be requested for individuals with clinical features suggestive of ciliary dysfunction or unexplained bronchiectasis.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the role of DNAL1 in ciliary function?
DNAL1 encodes a light chain component of the outer dynein arm complex, which generates the mechanical forces required for ciliary and flagellar beating. The protein helps maintain the structural integrity of the dynein motor and enables coordinated ciliary movement essential for airway clearance.
How are DNAL1 variants inherited?
DNAL1 follows an autosomal recessive inheritance pattern. An individual must inherit pathogenic variants in both copies of the gene (one from each parent) to develop associated ciliary dysfunction. Carriers with one altered copy typically remain unaffected.
Why is DNAL1 included on UK respiratory gene panels?
DNAL1 variants cause primary ciliary dyskinesia, a condition characterised by chronic respiratory infections and bronchiectasis. The gene's green status on NHS panels reflects sufficient evidence supporting its use in diagnostic testing for patients with unexplained respiratory ciliopathies and recurrent airway disease.