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ASNS
asparagine synthetase (glutamine-hydrolyzing)
The ASNS gene provides instructions for producing asparagine synthetase, an enzyme vital for the synthesis of the amino acid asparagine within cells. Asparagine synthetase is essential for converting aspartic acid into asparagine, playing a key role in protein production, ammonia detoxification, and brain signalling.
ASNS is located on the long (q) arm of chromosome 7, at band 7q21.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The ASNS gene encodes the enzyme asparagine synthetase, which is critically involved in the body's metabolism of amino acids. This enzyme is responsible for synthesising asparagine from aspartic acid, a process that also uses glutamine and produces glutamic acid. Asparagine is a non-essential amino acid required for numerous bodily functions, including protein synthesis and neuronal signalling.
Maintaining the correct balance of these amino acids is vital for cellular health. Impaired function of the ASNS gene can lead to a deficiency in asparagine production, particularly in the brain, which has significant neurological consequences.
What the gene does
The ASNS gene directs the creation of asparagine synthetase, an enzyme found throughout the body's cells. Its primary function is to catalyse the conversion of the amino acid aspartic acid into asparagine. This biochemical reaction requires glutamine, which is simultaneously converted into glutamic acid. Asparagine synthetase is crucial for upholding the proper balance of these four amino acids within the body.
Beyond protein synthesis, asparagine contributes to several other cellular processes. It assists in neutralising toxic ammonia, is important for protein modification, and is a precursor for certain neurotransmitters in the brain. Brain cells are particularly reliant on locally produced asparagine because this amino acid cannot cross the blood-brain barrier, making the ASNS enzyme indispensable for neurological function.
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Chromosome location
The ASNS gene is located on chromosome 7. Specifically, its chromosomal address is 7q21.3. This designation refers to the long (q) arm of chromosome 7, within region 21, band 3.
Protein structure
The asparagine synthetase protein consists of 561 amino acids and features two main functional regions. The N-terminal segment, spanning amino acids 2-191, contains the Glutamine amidotransferase type-2 domain. The central region, from amino acids 213-536, comprises the Asparagine synthetase domain, which is responsible for the enzyme's catalytic activity.
Key variants
Genetic variations within the ASNS gene can alter the function or production of the asparagine synthetase enzyme. These variants can range from single nucleotide changes to larger structural rearrangements. The impact of a specific variant depends on its location within the gene and how it affects the resulting protein's structure and activity.
Sample of pathogenic variants
3 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 |
|---|---|---|---|---|
g.(?_97481561)_(97498478_?)del | - | Pathogenic | ★☆☆☆ | not provided |
g.(?_97488515)_(97493818_?)del | - | Pathogenic | ★☆☆☆ | not provided |
g.(?_97498200)_(97498468_?)del | - | Pathogenic | ★☆☆☆ | not provided |
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 ASNS gene are associated with asparagine synthetase deficiency. This severe condition typically manifests with neurological symptoms shortly after birth. Such variants often result in an enzyme with significantly reduced or entirely absent function, impacting the brain's ability to produce essential asparagine.
No disease links recorded for this gene in our reference set.
UK clinical status
The ASNS gene is recognised within several NHS Genomic Medicine Service national testing panels. It is listed with a 'green' status in the Deciphering Developmental Disorders (DDG2P), Early onset or syndromic epilepsy, Foetal anomalies (R21), and Intellectual disability panels, indicating strong evidence for its association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main role of the ASNS gene?
The ASNS gene provides instructions for making the asparagine synthetase enzyme, which is responsible for converting aspartic acid into asparagine. This process is crucial for protein production, ammonia detoxification, and brain signalling.
Why is asparagine important for the brain?
Asparagine is vital for brain cells because it is needed to produce neurotransmitters and other essential molecules. Brain cells cannot import asparagine from the bloodstream, so they rely entirely on the asparagine synthetase enzyme (produced from the ASNS gene) to make their own supply.
What happens if the ASNS gene doesn't work correctly?
If the ASNS gene has pathogenic variants, it can lead to a deficiency in asparagine synthetase. This typically results in a condition called asparagine synthetase deficiency, which primarily causes severe neurological problems due to insufficient asparagine production in the brain.
References
- Lomelino CL, Andring JT, McKenna R. Asparagine synthetase: Function, structure, and role in disease. The Journal of biological chemistry. 2017. PMID: 29084849
- Alfadhel M, Alrifai MT, Trujillano D. Asparagine Synthetase Deficiency: New Inborn Errors of Metabolism. JIMD reports. 2015. PMID: 25663424
- Palmer EE, Hayner J, Sachdev R. Asparagine Synthetase Deficiency causes reduced proliferation of cells under conditions of limited asparagine. Molecular genetics and metabolism. 2015. PMID: 26318253