ASL variants cause argininosuccinate aciduria

Stable Identifier
R-HSA-9956529
Type
Pathway
Species
Homo sapiens
ReviewStatus
3/5
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ASL variants cause argininosuccinate aciduria
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Argininosuccinate lyase (ASL) is a homotetrameric enzyme that catalyzes the fourth reaction of the urea cycle, the cleavage of argininosuccinate to arginine and fumarate (Walker et al, 1990; Walker et al, 1997; Yu et al, 2001; reviewed in Nagmani et al, 2019). Mutations in ASL cause argininosuccinic aciduria (OMIM 207900), an autosomal recessive disorder that affects 1:70,000 to 1:218,000 live births (reviewed in Nagmani et al, 2019). Like other disorders of urea cycle enzymes, argininosuccinic aciduria is clinically diverse, with a severe neonatal form characterized by hyperammonemia, encephalopathy and respiratory alkalosis and a milder, late onset form that may be triggered by stress or infection (reviewed in Nagmani et al, 2019). Late onset alleles of ASL often retain residual activity, with heterozygous mutations interacting in vivo to restore a functional active site through intramolecular complementation (Yu et al, 2001; Trevisson et al, 2009; reviewed in Nagmani et al, 2019).
Literature References
PubMed ID Title Journal Year
2263616 Molecular analysis of human argininosuccinate lyase: mutant characterization and alternative splicing of the coding region

Walker, DC, McCloskey, DA, Simard, LR, McInnes, RR

Proc Natl Acad Sci U S A 1990
9045711 Intragenic complementation at the human argininosuccinate lyase locus. Identification of the major complementing alleles

Walker, DC, Christodoulou, J, Craig, HJ, Simard, LR, Ploder, L, Howell, PL, McInnes, RR

J Biol Chem 1997
21290785 Argininosuccinate Lyase Deficiency

Nagamani, SCS, Erez, A, Lee, B

2011
11747433 Mechanisms for intragenic complementation at the human argininosuccinate lyase locus

Yu, B, Thompson, GD, Yip, P, Howell, PL, Davidson, AR

Biochemistry 2001
19703900 Functional complementation in yeast allows molecular characterization of missense argininosuccinate lyase mutations

Trevisson, E, Burlina, A, Doimo, M, Pertegato, V, Casarin, A, Cesaro, L, Navas, P, Basso, G, Sartori, G, Salviati, L

J Biol Chem 2009
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Disease
Name Identifier Synonyms
argininosuccinic aciduria DOID:14755 arginosuccinase deficiency, Argininosuccinate lyase deficiency, deficiency of argininosuccinate lyase, argininosuccinic acidemia
Cross References
Mondo
Authored
Rothfels, K  (2025-07-02)
Created
Rothfels, K  (2025-06-12)
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