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    ASL argininosuccinate lyase [ Homo sapiens (human) ]

    Gene ID: 435, updated on 14-Nov-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (66075819..66093576)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (67297906..67315665)
    RS_2024_09 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 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. 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
    2. Bacterial expression of mutant argininosuccinate lyase reveals imperfect correlation of in-vitro enzyme activity with clinical phenotype in argininosuccinic aciduria. Engel K, et al. J Inherit Metab Dis, 2012 Jan. PMID 21667091
    3. Argininosuccinate Lyase Deficiency. Adam MP, et al. , 1993. PMID 21290785
    4. Reduced expression of argininosuccinate lyase is closely associated with postresectional survival in hepatocellular carcinoma: an immunohistochemistry study of 61 cases. Yang H, et al. Appl Immunohistochem Mol Morphol, 2012 Dec. PMID 22531684
    5. Distinct interactions of αA-crystallin with homologous substrate proteins, δ-crystallin and argininosuccinate lyase, under thermal stress. Chen YH, et al. Biochimie, 2011 Feb. PMID 20937351

    See all (62) 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)

    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 L-arginine biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in L-arginine biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in ammonia assimilation cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    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_2024_08

    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

    Gene LinkOut

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