On this page
ABCA3
ATP binding cassette subfamily A member 3
The ABCA3 gene encodes a protein vital for lung surfactant production, which is crucial for normal breathing and preventing alveolar collapse. The ABCA3 gene provides instructions for creating a protein involved in the production of pulmonary surfactant, a substance lining the lungs that facilitates easy breathing.
ABCA3 is located on the short (p) arm of chromosome 16, at band 16p13.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 16 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The ABCA3 gene, also known as ATP binding cassette subfamily A member 3, plays a critical role in human respiratory health. It is essential for the proper formation and function of lung surfactant, a complex mixture of lipids and proteins. This substance reduces surface tension within the alveoli, preventing them from collapsing and ensuring efficient gas exchange in the lungs.
What the gene does
The protein encoded by the ABCA3 gene is an ATP-binding cassette (ABC) transporter. It is located within the membrane of lamellar bodies, which are specialised organelles in lung cells where surfactant components are processed and stored. The ABCA3 protein is responsible for transporting phospholipids into these lamellar bodies, where they combine with surfactant proteins to form functional surfactant. This transport function is crucial not only for the assembly of surfactant but also for the proper maturation of surfactant proteins. Without a properly functioning ABCA3 protein, the normal packaging and processing of surfactant are impaired, leading to surfactant dysfunction and severe respiratory issues.
Video: Genetics 101
Chromosome location
The ABCA3 gene is situated on chromosome 16 at position 16p13.3. This specific location indicates its position on the short arm of chromosome 16, within band 13.3.
Protein structure
The ABCA3 protein consists of 1704 amino acids. It features two prominent ABC transporter domains. The first ABC transporter domain is located between amino acids 530 and 763, and the second ABC transporter domain spans amino acids 1381 to 1614. These domains are characteristic of ABC transporters and are essential for the protein's function in ATP binding and substrate transport.
Key variants
Variants in the ABCA3 gene can affect the protein's ability to facilitate surfactant production, leading to various degrees of respiratory dysfunction. Over 100 different variants have been identified that can impair the gene's function. The clinical impact of these variants can range from severe, life-threatening respiratory distress in neonates to milder, more gradual onset breathing problems in older children or adults.
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.127C>T | p.Arg43Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary pulmonary alveolar proteinosis |
c.128G>A | p.Arg43His | Pathogenic/Likely pathogenic | ★★☆☆ | Primary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies |
c.1303C>T | p.Arg435Ter | Pathogenic | ★★☆☆ | Interstitial lung disease due to ABCA3 deficiency |
c.1455C>G | p.Tyr485Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary pulmonary alveolar proteinosis |
c.1474dup | p.Tyr492fs | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.1729_1730del | p.Ser577fs | Pathogenic | ★★☆☆ | not provided |
c.1890C>A | p.Tyr630Ter | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.2188_2189dup | p.Asp731fs | Pathogenic/Likely pathogenic | ★★☆☆ | Interstitial lung disease due to ABCA3 deficiency |
c.2404_2405del | p.Ser802fs | Pathogenic | ★★☆☆ | ABCA3-related disorder |
c.2741A>G | p.Lys914Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Interstitial lung disease due to ABCA3 deficiency |
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 ABCA3 gene are primarily associated with ABCA3 deficiency, a condition that manifests as severe surfactant dysfunction. This can lead to profound breathing difficulties, particularly in newborns. In some cases, ABCA3 gene variants have also been implicated in conditions like idiopathic pulmonary fibrosis, though the primary association remains with surfactant-related lung diseases.
UK clinical status
The ABCA3 gene is an important focus for genetic testing within the UK National Health Service. It is currently featured on several NHS Genomic Medicine Service panels, including those for Childhood interstitial lung disease (R462), Familial pulmonary fibrosis (R421), and Surfactant deficiency (R192), indicating its established role in these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the ABCA3 gene?
The ABCA3 gene provides instructions for a protein that transports phospholipids into lamellar bodies in lung cells. This process is essential for the production and proper function of pulmonary surfactant, which lines the lungs and aids breathing.
What health conditions are associated with variants in the ABCA3 gene?
Variants in the ABCA3 gene are primarily associated with ABCA3 deficiency, which can cause severe breathing problems due to surfactant dysfunction. It may also play a role in idiopathic pulmonary fibrosis.
How does ABCA3 deficiency affect breathing?
In ABCA3 deficiency, the body cannot produce enough functional surfactant. Without adequate surfactant, the air sacs in the lungs (alveoli) can collapse, making it very difficult to breathe and impairing oxygen delivery to the body.
References
- Matsumura Y, Ban N, Inagaki N. Aberrant catalytic cycle and impaired lipid transport into intracellular vesicles in ABCA3 mutants associated with nonfatal pediatric interstitial lung disease. American journal of physiology. Lung cellular and molecular physiology. 2008. PMID: 18676873
- Cheong N, Zhang H, Madesh M. ABCA3 is critical for lamellar body biogenesis in vivo. The Journal of biological chemistry. 2007. PMID: 17540762
- Brasch F, Schimanski S, Mühlfeld C. Alteration of the pulmonary surfactant system in full-term infants with hereditary ABCA3 deficiency. American journal of respiratory and critical care medicine. 2006. PMID: 16728712
- Matsumura Y, Ban N, Ueda K. Characterization and classification of ATP-binding cassette transporter ABCA3 mutants in fatal surfactant deficiency. The Journal of biological chemistry. 2006. PMID: 16959783