Gene: ASL

Alternate names for this Gene: ASAL

Gene Summary: This gene encodes a member of the lyase 1 family. The encoded protein forms a cytosolic homotetramer and primarily catalyzes the reversible hydrolytic cleavage of argininosuccinate into arginine and fumarate, an essential step in the liver in detoxifying ammonia via the urea cycle. Mutations in this gene result in the autosomal recessive disorder argininosuccinic aciduria, or argininosuccinic acid lyase deficiency. A nontranscribed pseudogene is also located on the long arm of chromosome 22. Alternatively spliced transcript variants encoding different isoforms have been described.

Gene is located in Chromosome: 7

Location in Chromosome : 7q11.21

Description of this Gene: argininosuccinate lyase

Type of Gene: protein-coding

rs1329070853 in ASL gene and Argininosuccinic Aciduria PMID 16941645 2006 Deletion hotspot in the argininosuccinate lyase gene: association with topoisomerase II and DNA polymerase alpha sites.

PMID 24166829 2014 Mutations and polymorphisms in the human argininosuccinate lyase (ASL) gene.

PMID 12384776 2002 Argininosuccinate lyase (ASL) deficiency: mutation analysis in 27 patients and a completed structure of the human ASL gene.

PMID 2263616 1990 Molecular analysis of human argininosuccinate lyase: mutant characterization and alternative splicing of the coding region.

PMID 12408190 2002 Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in five unrelated families.

PMID 17326097 2007 Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novel ASL pseudogene.

PMID 19703900 2009 Functional complementation in yeast allows molecular characterization of missense argininosuccinate lyase mutations.

PMID 1705937 1991 Analysis of naturally occurring and site-directed mutations in the argininosuccinate lyase gene.

PMID 11747432 2001 Three-dimensional structure of the argininosuccinate lyase frequently complementing allele Q286R.

PMID 20236848 2010 Long-term outcome of patients with argininosuccinate lyase deficiency diagnosed by newborn screening in Austria.

PMID 25778938 2015 Unstable argininosuccinate lyase in variant forms of the urea cycle disorder argininosuccinic aciduria.

PMID 26661037 2016 Corpus callosum abnormalities: neuroradiological and clinical correlations.

PMID 22231378 2012 Yeast complementation is sufficiently sensitive to detect the residual activity of ASL alleles associated with mild forms of argininosuccinic aciduria.

PMID 21667091 2012 Bacterial expression of mutant argininosuccinate lyase reveals imperfect correlation of in-vitro enzyme activity with clinical phenotype in argininosuccinic aciduria.

PMID 18616627 2008 Hereditary urea cycle diseases in Finland.

PMID 26745957 2016 Effect of Cysteamine on Mutant ASL Proteins with Cysteine for Arginine Substitutions.

PMID 27515243 2017 Argininosuccinic Acid Lyase Deficiency Missed by Newborn Screen.

PMID 2263616 1990 We conclude (i) that the identification of the R95C mutation in strain 944 demonstrates that virtually all ASAL deficiency results from defects in the ASAL structural gene and (ii) that minor alternative splicing of the coding region occurs at the ASAL locus.

PMID 23430928 2012 The ketogenic diet is well tolerated and can be effective in patients with argininosuccinate lyase deficiency and refractory epilepsy.

PMID 9686346 1998 Intragenic complementation at the argininosuccinate lyase locus: reconstruction of the active site.

PMID 9045711 1997 Intragenic complementation at the human argininosuccinate lyase locus. Identification of the major complementing alleles.

PMID 15273245 2004 Disruption of a salt bridge dramatically accelerates subunit exchange in duck delta2 crystallin.

PMID 11747433 2001 Mechanisms for intragenic complementation at the human argininosuccinate lyase locus.

PMID 16435180 2005 A further 28 patients with a confirmed diagnosis of ASAuria based on MS/MS of their DBS were tested by sequencing for the presence of the Q354X mutation.

PMID 25525159 2015 RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

PMID 20298553 2010 Novel mutations underlying argininosuccinic aciduria in Saudi Arabia.

PMID 21744316 2011 Epilepsy and argininosuccinic aciduria.

PMID 9256435 1997 The mutations involved in the most successful complementation event observed in ASL deficiency were found to be an aspartate to glycine mutation at codon 87 of one allele (D87G) coupled with a glutamine to arginine mutation at codon 286 of the other (Q286R).

PMID 11747433 2001 The detection and characterization of a novel complementation event between the A398D and D87G mutants has shown how complementation in patients with argininosuccinic aciduria may correlate with the clinical phenotype.

PMID 25433810 2014 Urea cycle disorders in Spain: an observational, cross-sectional and multicentric study of 104 cases.

PMID 22081021 2011 Requirement of argininosuccinate lyase for systemic nitric oxide production.

PMID 24136197 2013 Understanding the role of argininosuccinate lyase transcript variants in the clinical and biochemical variability of the urea cycle disorder argininosuccinic aciduria.

PMID 10896281 2000 Two novel mutations (E86A, R113W) in argininosuccinate lyase deficiency and evidence for highly variable splicing of the human argininosuccinate lyase gene.

PMID 28251416 2017 Expanding the phenotype in argininosuccinic aciduria: need for new therapies.

rs313829 in ASL gene and Blood Protein Measurement PMID 29875488 2018 Genomic atlas of the human plasma proteome.

PMID 30072576 2018 Co-regulatory networks of human serum proteins link genetics to disease.