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ASL argininosuccinate lyase [ Homo sapiens (human) ]

Gene ID: 435, updated on 7-Apr-2024

Summary

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Official Symbol
ASLprovided by HGNC
Official Full Name
argininosuccinate lyaseprovided by HGNC
Primary source
HGNC:HGNC:746
See related
Ensembl:ENSG00000126522 MIM:608310; AllianceGenome:HGNC:746
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ASAL
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. [provided by RefSeq, Jul 2008]
Expression
Broad expression in liver (RPKM 45.2), kidney (RPKM 25.5) and 24 other tissues See more
Orthologs
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Genomic context

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See ASL in Genome Data Viewer
Location:
7q11.21
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (66075819..66093576)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (67297906..67315665)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (65540806..65558563)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105375336 Neighboring gene CGRP receptor component pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:65509069-65509569 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:65516808-65516986 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26079 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18203 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26080 Neighboring gene golgin A7 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:65551291-65551918 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:65565192-65565753 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:65578710-65578900 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26081 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:65580214-65580742 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr7:65612993-65614192 Neighboring gene CGRP receptor component Neighboring gene ReSE screen-validated silencer GRCh37_chr7:65642926-65643089 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18204 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18205 Neighboring gene tyrosylprotein sulfotransferase 1 Neighboring gene MPRA-validated peak6545 silencer Neighboring gene NANOG hESC enhancer GRCh37_chr7:65779787-65780442 Neighboring gene RNA, U6 small nuclear 313, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Biomarkers for liver disease in urea cycle disorders. Nagamani SCS, et al. Mol Genet Metab, 2021 Jun. PMID 33846069, Free PMC Article
  2. From genotype to phenotype: Early prediction of disease severity in argininosuccinic aciduria. Zielonka M, et al. Hum Mutat, 2020 May. PMID 31943503, Free PMC Article
  3. Whole-Exome Sequencing Identified a Novel Compound Heterozygous Genotype in ASL in a Chinese Han Patient with Argininosuccinate Lyase Deficiency. Zhao M, et al. Biomed Res Int, 2019. PMID 31183366, Free PMC Article
  4. Argininosuccinate lyase interacts with cyclin A2 in cytoplasm and modulates growth of liver tumor cells. Hung YH, et al. Oncol Rep, 2017 Feb. PMID 28035420, Free PMC Article
  5. Silencing of argininosuccinate lyase inhibits colorectal cancer formation. Huang HL, et al. Oncol Rep, 2017 Jan. PMID 27840980

See all (59) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Argininosuccinate lyase deficiency causes blood-brain barrier disruption via nitric oxide-mediated dysregulation of claudin expression.
    Title: Argininosuccinate lyase deficiency causes blood-brain barrier disruption via nitric oxide-mediated dysregulation of claudin expression.
  2. Variants associated with urea cycle disorders in Japanese patients: Nationwide study and literature review.
    Title: Variants associated with urea cycle disorders in Japanese patients: Nationwide study and literature review.
  3. Biomarkers for liver disease in urea cycle disorders.
    Title: Biomarkers for liver disease in urea cycle disorders.
  4. From genotype to phenotype: Early prediction of disease severity in argininosuccinic aciduria.
    Title: From genotype to phenotype: Early prediction of disease severity in argininosuccinic aciduria.
  5. Clinical and genetic analysis of five Chinese patients with urea cycle disorders.
    Title: Clinical and genetic analysis of five Chinese patients with urea cycle disorders.
  6. Mechanistically, KLF7 transcriptionally activated argininosuccinate lyase (ASL), which was observed highly expressed in glioma tissues. KLF7 potentiates polyamine biosynthesis and glioma cell growth via transcriptionally activates ASL.
    Title: KLF7 promotes polyamine biosynthesis and glioma development through transcriptionally activating ASL.
  7. Compound heterozygous p.Lys69Arg and p.Arg213 * mutations that resulted in reduced ASL enzyme activity were found in a patient with ASLD.
    Title: Whole-Exome Sequencing Identified a Novel Compound Heterozygous Genotype in ASL in a Chinese Han Patient with Argininosuccinate Lyase Deficiency.
  8. The remaining five patients were diagnosed with neonatal intrahepatic cholestasis due to citrin deficiency, and have respectively carried mutations of the SLC25A13 gene including [c.851-854delGTAT+c.851-854delGTAT], [c.851-854delGTAT+IVS6+5G>A], [c.851-854delGTAT+IVS16ins3kb], [c.851-854delGTAT+IVS6-11A>G] and [c.851-854delGTAT+c.1638-1660dup23]
    Title: [Mutational analysis of ASS1, ASL and SLC25A13 genes in six Chinese patients with citrullinemia].
  9. Overexpression of ASL may be a contributing factor in drug resistance for arginine deprivation therapy.
    Title: Argininosuccinate lyase interacts with cyclin A2 in cytoplasm and modulates growth of liver tumor cells.
  10. ASL-targeting shRNA-induced growth inhibition is associated with decreased cyclin A2 expression and Nitric oxide content in colon cancer.
    Title: Silencing of argininosuccinate lyase inhibits colorectal cancer formation.
Submit: New GeneRIF Correction See all GeneRIFs (27)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables argininosuccinate lyase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables argininosuccinate lyase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in ammonia assimilation cycle IEA
Inferred from Electronic Annotation
more info
  
involved_in arginine biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in arginine biosynthetic process via ornithine IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in arginine metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in locomotory behavior IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of nitric oxide biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in post-embryonic development IEA
Inferred from Electronic Annotation
more info
  
involved_in urea cycle IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytoplasm TAS
Traceable Author Statement
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 

General protein information

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Preferred Names
argininosuccinate lyase
Names
argininosuccinase
arginosuccinase
NP_000039.2
NP_001020114.1
NP_001020115.1
NP_001020117.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_009288.1 RefSeqGene

    Range
    5031..22788
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000048.4 → NP_000039.2  argininosuccinate lyase isoform 1

    See identical proteins and their annotated locations for NP_000039.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AC068533, AI469765, BC008195, BX328836
    Consensus CDS
    CCDS5531.1
    UniProtKB/Swiss-Prot
    E7EMI0, E9PE48, P04424, Q6LDS5, Q96HS2
    UniProtKB/TrEMBL
    A0A024RDL8, F8W943
    Related
    ENSP00000307188.9, ENST00000304874.14
    Conserved Domains (2) summary
    cd01359
    Location:27 → 459
    Argininosuccinate_lyase; Argininosuccinate lyase (argininosuccinase, ASAL)
    PLN02646
    Location:1 → 463
    PLN02646; argininosuccinate lyase

  2. NM_001024943.2 → NP_001020114.1  argininosuccinate lyase isoform 1

    See identical proteins and their annotated locations for NP_001020114.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. Variants 1 and 2 encode the longest isoform (1).
    Source sequence(s)
    AC068533, AI469765, BQ949510
    Consensus CDS
    CCDS5531.1
    UniProtKB/Swiss-Prot
    E7EMI0, E9PE48, P04424, Q6LDS5, Q96HS2
    UniProtKB/TrEMBL
    A0A024RDL8, F8W943
    Related
    ENSP00000378741.3, ENST00000395332.8
    Conserved Domains (2) summary
    cd01359
    Location:27 → 459
    Argininosuccinate_lyase; Argininosuccinate lyase (argininosuccinase, ASAL)
    PLN02646
    Location:1 → 463
    PLN02646; argininosuccinate lyase

  3. NM_001024944.2 → NP_001020115.1  argininosuccinate lyase isoform 2

    See identical proteins and their annotated locations for NP_001020115.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate, in-frame exon, compared to variant 1, resulting in a shorter protein (isoform 2).
    Source sequence(s)
    AC068533, AI469765, BQ949510, BU634268
    Consensus CDS
    CCDS47597.1
    UniProtKB/TrEMBL
    F8W943
    Related
    ENSP00000378740.3, ENST00000395331.4
    Conserved Domains (2) summary
    cd01359
    Location:27 → 439
    Argininosuccinate_lyase; Argininosuccinate lyase (argininosuccinase, ASAL)
    PLN02646
    Location:1 → 443
    PLN02646; argininosuccinate lyase

  4. NM_001024946.2 → NP_001020117.1  argininosuccinate lyase isoform 3

    See identical proteins and their annotated locations for NP_001020117.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an alternate, in-frame exon, compared to variant 1, resulting in a shorter protein (isoform 3).
    Source sequence(s)
    AC068533, AI469765, BQ949510
    Consensus CDS
    CCDS47598.1
    UniProtKB/TrEMBL
    A0A0S2Z316, A0A0S2Z3B0
    Related
    ENSP00000370219.4, ENST00000380839.9
    Conserved Domains (2) summary
    cd01359
    Location:27 → 433
    Argininosuccinate_lyase; Argininosuccinate lyase (argininosuccinase, ASAL)
    PLN02646
    Location:1 → 437
    PLN02646; argininosuccinate lyase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    66075819..66093576
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    67297906..67315665
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P04424.4 GenPept UniProtKB/Swiss-Prot:P04424

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