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CTSA
cathepsin A
The CTSA gene provides instructions for producing cathepsin A, a lysosomal enzyme essential for the breakdown and recycling of various cellular components. Cathepsin A, encoded by the CTSA gene, functions as both a protease, breaking down other proteins, and a protective protein, preventing premature degradation of associated enzymes.
CTSA is located on the long (q) arm of chromosome 20, at band 20q13.12. Arm ratio per GRCh38 - banding schematic.
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Overview
The CTSA gene encodes a protein known as cathepsin A, also referred to as protective protein/cathepsin A (PPCA). This protein plays a critical role in cellular waste management and recycling, specifically within compartments called lysosomes. Cathepsin A contributes to maintaining cellular health by ensuring the proper degradation of unwanted molecules.
Dysfunction of the CTSA gene is associated with inherited conditions, highlighting its importance in normal physiological processes. Understanding the role of CTSA can provide insights into lysosomal storage disorders and related neurogenetic conditions.
What the gene does
The cathepsin A protein, encoded by the CTSA gene, performs dual functions within the cell. It acts as a protease, cleaving and breaking down other proteins into smaller components. Additionally, cathepsin A serves as a protective protein, forming complexes with other enzymes like beta-galactosidase and neuraminidase 1 to prevent their premature degradation.
These activities primarily occur in lysosomes, which are cellular organelles responsible for the digestion and recycling of cellular waste. Within lysosomes, cathepsin A facilitates the breakdown of complex sugar molecules, such as oligosaccharides attached to glycoproteins and glycolipids. On the cell surface, cathepsin A is part of a complex with neuraminidase 1 and elastin-binding protein, forming the elastin-binding protein receptor, which is involved in creating elastic fibres in connective tissues.
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Chromosome location
The CTSA gene is located on chromosome 20, specifically at position 20q13.12. This genomic address specifies its precise location on the long (q) arm of chromosome 20. The gene spans a defined region of the human genome, providing the blueprint for the cathepsin A protein.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the CTSA gene can alter the structure or function of the cathepsin A protein. These genetic changes can range from small alterations, such as single nucleotide polymorphisms (SNPs), to larger deletions or insertions affecting several base pairs. The impact of a variant depends on its location within the gene and how it affects protein production or activity, potentially leading to reduced or absent protein function.
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.1005del | p.Ala336fs | Pathogenic/Likely pathogenic | ★★☆☆ | Combined deficiency of sialidase AND beta galactosidase |
c.1019dup | p.Tyr340Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Combined deficiency of sialidase AND beta galactosidase |
c.1104dup | p.Gln369fs | Pathogenic | ★★☆☆ | Combined deficiency of sialidase AND beta galactosidase |
c.1105C>T | p.Gln369Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Combined deficiency of sialidase AND beta galactosidase |
c.1-2A>G | - | Pathogenic/Likely pathogenic | ★★☆☆ | Combined deficiency of sialidase AND beta galactosidase |
c.143del | p.Arg48fs | Pathogenic | ★★☆☆ | Combined deficiency of sialidase AND beta galactosidase |
c.376del | p.Leu126fs | Pathogenic/Likely pathogenic | ★★☆☆ | Combined deficiency of sialidase AND beta galactosidase |
c.625_626del | p.Ser209fs | Pathogenic/Likely pathogenic | ★★☆☆ | Combined deficiency of sialidase AND beta galactosidase |
c.843T>A | p.Cys281Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Combined deficiency of sialidase AND beta galactosidase |
c.963_964del | p.Gly322_Asp323insTer | Pathogenic/Likely pathogenic | ★★☆☆ | Combined deficiency of sialidase AND beta galactosidase |
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 CTSA gene are known to cause galactosialidosis, an inherited lysosomal storage disorder. This condition affects multiple body systems, with symptoms varying based on the age of onset. Galactosialidosis can present with a range of features, often impacting the heart, skeleton, vision, and hearing.
UK clinical status
The CTSA gene is recognised in the UK by NHS England's Genomic Medicine Service, featuring on several national testing panels. These include panels for conditions such as DDG2P, Foetal anomalies (R21), Foetal hydrops, Intellectual disability, Leukodystrophy (adult onset, R62), Likely inborn error of metabolism (R98), Lysosomal storage disorder (R276), Neurodegenerative disorders (adult onset), Skeletal dysplasia (R104), and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the CTSA gene?
The CTSA gene provides instructions for cathepsin A, a protein that acts as both a protease and a protective protein within cellular lysosomes. It helps break down and recycle cellular waste, particularly complex sugar molecules.
What condition is associated with CTSA gene variants?
Variants in the CTSA gene are known to cause galactosialidosis, a lysosomal storage disorder that can affect various body systems, including the heart, skeleton, vision, and hearing.
Where is the CTSA gene located?
The CTSA gene is located on chromosome 20, specifically at position 20q13.12. This is on the long (q) arm of chromosome 20.
References
- Matsumoto N, Gondo K, Kukita J. A case of galactosialidosis with a homozygous Q49R point mutation. Brain & development. 2008. PMID: 18396002
- Hinek A, Pshezhetsky AV, von Itzstein M. Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly. The Journal of biological chemistry. 2006. PMID: 16314420
- Malvagia S, Morrone A, Caciotti A. New mutations in the PPBG gene lead to loss of PPCA protein which affects the level of the beta-galactosidase/neuraminidase complex and the EBP-receptor. Molecular genetics and metabolism. 2004. PMID: 15110321
- Groener J, Maaswinkel-Mooy P, Smit V. New mutations in two Dutch patients with early infantile galactosialidosis. Molecular genetics and metabolism. 2003. PMID: 12649068
- Takiguchi K, Itoh K, Shimmoto M. Structural and functional study of K453E mutant protective protein/cathepsin A causing the late infantile form of galactosialidosis. Journal of human genetics. 2000. PMID: 10944848
- Hiraiwa M. Cathepsin A/protective protein: an unusual lysosomal multifunctional protein. Cellular and molecular life sciences : CMLS. 1999. PMID: 11212324