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ASNS
asparagine synthetase (glutamine-hydrolyzing)
The ASNS gene provides instructions for making asparagine synthetase, an enzyme crucial for producing the amino acid asparagine, particularly important for brain function. The ASNS gene codes for the enzyme asparagine synthetase, which converts aspartic acid into asparagine.
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, or asparagine synthetase (glutamine-hydrolysing), encodes an enzyme called asparagine synthetase. This enzyme plays a fundamental role in amino acid metabolism by catalysing the conversion of aspartic acid to asparagine, utilising glutamine as a nitrogen donor.
Asparagine is an amino acid essential for building proteins, detoxifying ammonia, and forming neurotransmitters. While the body can obtain asparagine from diet, brain cells are unique in their reliance on asparagine synthetase for its production, as asparagine cannot cross the blood-brain barrier.
What the gene does
The asparagine synthetase enzyme, encoded by the ASNS gene, is responsible for maintaining the balance of specific amino acids within cells. Its primary function involves the synthesis of asparagine from aspartic acid, with glutamine providing the necessary nitrogen atom. During this reaction, glutamine is converted to glutamic acid.
Asparagine plays multiple critical roles: it is a building block for many proteins, aids in the removal of toxic ammonia from cells, contributes to protein modification processes, and is involved in the synthesis of certain neurotransmitter molecules. The brain's dependence on this enzyme for its asparagine supply underscores its importance, as dietary asparagine cannot enter the brain due to the blood-brain barrier.
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Chromosome location
The ASNS gene is located on chromosome 7, specifically at position 7q21.3. This chromosomal location indicates where the gene is found within the human genome.
Protein structure
The asparagine synthetase protein is 561 amino acids in length and comprises two main domains. The Glutamine amidotransferase type-2 domain spans amino acids 2-191. Following this, the Asparagine synthetase domain is located between amino acids 213-536, which is crucial for its enzymatic function.
Key variants
Variants within the ASNS gene can alter the function of the asparagine synthetase enzyme. These genetic changes may disrupt the enzyme's ability to produce asparagine effectively, leading to downstream consequences for cellular metabolism and neurological health. Further details on specific variants are available through clinical databases.
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 primarily associated with asparagine synthetase deficiency. This condition typically presents with severe neurological problems appearing shortly after birth. Affected individuals often exhibit significant impairment in the enzyme's function, leading to a shortage of asparagine, particularly within the brain.
No disease links recorded for this gene in our reference set.
UK clinical status
The ASNS gene is included on several NHS Genomic Medicine Service clinical panels in the UK, reflecting its recognised clinical significance. It is part of the DDG2P panel, as well as panels for Early onset or syndromic epilepsy, Foetal anomalies (R21), and Intellectual disability, all of which are designated green, indicating their clinical utility.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the ASNS gene?
The ASNS gene provides instructions for creating the asparagine synthetase enzyme. This enzyme is essential for converting aspartic acid into asparagine, an amino acid vital for protein synthesis, ammonia detoxification, and brain neurotransmitter production.
Why is asparagine production by ASNS particularly important for the brain?
Asparagine cannot cross the blood-brain barrier. Therefore, brain cells rely exclusively on the asparagine synthetase enzyme, produced by the ASNS gene, to synthesise the asparagine they need for various critical functions.
What health condition is associated with ASNS gene variants?
Variants in the ASNS gene are primarily linked to asparagine synthetase deficiency. This rare condition typically causes severe neurological issues that manifest early in life due to impaired asparagine synthesis.
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