Asparagine Synthetase

Alternative Names

  • ASNS
  • Human Complement for Hamster Temperature-Sensitive Mutant ts11
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OMIM Number

108370

Gene Map Locus
7q21.3

Description

The ASNS gene codes for the glutamine-dependent asparagine synthetase enzyme that catalyzes the transfer of ammonia from glutamine to aspartic acid via a β-aspartyl-AMP intermediate to form asparagine.  This gene complements a mutation in the temperature-sensitive hamster mutant ts11, which blocks progression through the G1 phase of the cell cycle at nonpermissive temperature.  

Mutations in this gene cause Asparagine Synthetase Deficiency, an extremely rare neurodevelopmental disorder, characterized by congenital microcephaly, severely delayed psychomotor development, progressive encephalopathy, and cortical atrophy, associated with seizure or hyperekplexia.  Asparagine Synthetase is used clinically as one of the components in multi-agent treatment protocol of childhood Acute Lymphoblastic Leukemia. 

Molecular Genetics

The ASNS gene is located on chromosome 7q21.3, where is spans a length of 35kb.  It contains 13 exons and has at least 14 spliced coding transcript variants.  The first three exons are non-coding.  The promotor of this gene is located within a GC-rich sequence, and is followed by two nutrient sensing response elements.  The Asparagine synthetase protein consists of 561 amino acid residues with a molecular mass of 64 kDa.  The protein is expressed in all tissues, but has a particularly high expression level in the adult brain, especially during neuronal development.  

To date, only a handful of pathogenic mutations in this gene have been reported to cause asparagine synthetase deficiency. 

Epidemiology in the Arab World

View Map
Variant NameCountryGenomic LocationClinical SignificanceCondition(s)HGVS ExpressionsdbSNPClinvar
NM_001673.4:c.146G>AUnited Arab EmiratesNC_000007.14:g.97869011C>TLikely Pathogenic,Uncertain SignificanceAsparagine Synthetase DeficiencyNG_033870.2:g.64552G>A; NM_001673.4:c.146G>A; NP_001664.3:p.Arg49Gln769236847383733
NM_133436.3:c.1193A>CUnited Arab EmiratesNC_000007.14:g.97854625T>GLikely Pathogenic,Uncertain SignificanceAsparagine Synthetase DeficiencyNG_033870.2:g.78938A>C; NM_133436.3:c.1193A>C; NP_597680.2:p.Tyr398Ser1166271142800997

Other Reports

Saudi Arabia

Seidahmed et al., (2016) described two unrelated Saudi patients born to consanguineous parents, with typical clinical and radiological presentations of ASNSD (asparagine synthetase deficiency).  Whole exome sequencing identified a homozygous novel p.Arg324* mutation in the ASNS gene in the first patient and a novel p. Tyr315Cys mutation in the ASNS gene in the second patient.  These two mutations were predicted to be pathogenic by PolyPhen, SIFT and CADD programs.

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