On this page
AGA
aspartylglucosaminidase
The AGA gene provides instructions for creating the aspartylglucosaminidase enzyme, which is crucial for breaking down complex sugar molecules in cellular recycling centres called lysosomes. The AGA gene encodes the aspartylglucosaminidase enzyme, vital for the proper functioning of lysosomes within cells.
AGA is located on the long (q) arm of chromosome 4, at band 4q34.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 4 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The AGA gene, or aspartylglucosaminidase gene, plays a fundamental role in human cellular metabolism. It contains the genetic blueprint for an enzyme with the same name, which is essential for processing certain complex molecules within the body's cells. Proper function of this enzyme is critical for maintaining cellular health, particularly within the lysosome, a key cellular organelle.
What the gene does
The AGA gene directs the production of aspartylglucosaminidase, an enzyme primarily active within lysosomes. Lysosomes function as the cell's recycling centres, breaking down and processing waste materials. The aspartylglucosaminidase enzyme specifically cleaves glycoproteins - proteins with attached sugar chains (oligosaccharides). This enzyme is responsible for cutting the bond between an asparagine amino acid and an N-acetylglucosamine sugar molecule within these glycoproteins. This specific cutting action is one of the final stages in the complete degradation of glycoproteins within the lysosome, ensuring proper cellular waste management and nutrient recycling.
Video: Genetics 101
Chromosome location
The AGA gene is situated on chromosome 4, specifically at position 4q34.3. This genomic location refers to the long (q) arm of chromosome 4, in region 3, band 4, sub-band 3.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the AGA gene can alter the function or production of the aspartylglucosaminidase enzyme. These genetic changes can range from single nucleotide substitutions to larger deletions or duplications. The nature and location of a variant can influence the severity of its impact on enzyme activity and, consequently, the associated health outcomes.
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.101_107del | p.Trp34fs | Pathogenic | ★★☆☆ | Aspartylglucosaminuria |
c.1018G>T | p.Glu340Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Aspartylglucosaminuria |
c.128-2A>G | - | Pathogenic | ★★☆☆ | Aspartylglucosaminuria |
c.187dup | p.Met63fs | Pathogenic | ★★☆☆ | Aspartylglucosaminuria |
c.192del | p.Cys64fs | Pathogenic/Likely pathogenic | ★★☆☆ | Aspartylglucosaminuria |
c.198_201del | p.Arg66fs | Pathogenic/Likely pathogenic | ★★☆☆ | Aspartylglucosaminuria |
c.1A>G | p.Met1Val | Pathogenic/Likely pathogenic | ★★☆☆ | Aspartylglucosaminuria |
c.200_201del | p.Glu67fs | Pathogenic | ★★☆☆ | Aspartylglucosaminuria |
c.214T>C | p.Ser72Pro | Pathogenic | ★★☆☆ | Aspartylglucosaminuria |
c.302C>T | p.Ala101Val | Pathogenic/Likely pathogenic | ★★☆☆ | Aspartylglucosaminuria |
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 AGA gene are known to cause aspartylglucosaminuria, an inherited metabolic disorder. This condition primarily affects neurological function and movement, and typically worsens over time as metabolic waste products accumulate in cells due to impaired enzyme activity.
UK clinical status
The AGA gene is included on several UK NHS National Genomic Test Directory panels, indicating its clinical significance for diagnostic testing. It is listed as 'green' on panels such as DDG2P, Intellectual disability, Likely inborn error of metabolism (R98), Lysosomal storage disorder (R276), 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 AGA gene?
The AGA gene provides instructions for the aspartylglucosaminidase enzyme, which breaks down specific complex sugar molecules called glycoproteins within the cell's lysosomes, acting as a crucial part of the cellular recycling process.
What health condition is associated with variants in the AGA gene?
Variants in the AGA gene are associated with aspartylglucosaminuria, an inherited metabolic disorder characterised by progressive neurological and movement difficulties due to impaired lysosomal function.
How does the aspartylglucosaminidase enzyme work?
The aspartylglucosaminidase enzyme specifically cuts the bond between an asparagine amino acid and an N-acetylglucosamine sugar molecule in glycoproteins. This action is a key step in the complete degradation of these molecules within lysosomes.
References
- Saarela J, Oinonen C, Jalanko A. Autoproteolytic activation of human aspartylglucosaminidase. The Biochemical journal. 2004. PMID: 14616088
- Saarela J, Laine M, Oinonen C. Molecular pathogenesis of a disease: structural consequences of aspartylglucosaminuria mutations. Human molecular genetics. 2001. PMID: 11309371
- Aronson NN Jr. Aspartylglycosaminuria: biochemistry and molecular biology. Biochimica et biophysica acta. 1999. PMID: 10571008