U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

ADSL adenylosuccinate lyase [ Homo sapiens (human) ]

Gene ID: 158, updated on 3-Apr-2024

Summary

Go to the top of the page Help
Official Symbol
ADSLprovided by HGNC
Official Full Name
adenylosuccinate lyaseprovided by HGNC
Primary source
HGNC:HGNC:291
See related
Ensembl:ENSG00000239900 MIM:608222; AllianceGenome:HGNC:291
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
ASL; AMPS; ASASE
Summary
The protein encoded by this gene belongs to the lyase 1 family. It is an essential enzyme involved in purine metabolism, and catalyzes two non-sequential reactions in the de novo purine biosynthetic pathway: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and the conversion of adenylosuccinate (S-AMP) to adenosine monophosphate (AMP). Mutations in this gene are associated with adenylosuccinase deficiency (ADSLD), a disorder marked with psychomotor retardation, epilepsy or autistic features. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]
Expression
Ubiquitous expression in lymph node (RPKM 10.5), testis (RPKM 9.0) and 25 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
22q13.1
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (40346500..40387527)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (40817910..40858924)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (40742504..40783531)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene trinucleotide repeat containing adaptor 6B Neighboring gene ribosomal protein L7 pseudogene 52 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19082 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:40591286-40591820 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:40591821-40592353 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19083 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:40624195-40624696 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:40633809-40634710 Neighboring gene uncharacterized LOC124905121 Neighboring gene MPRA-validated peak4496 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr22:40740204-40740376 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:40742019-40742532 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:40742533-40743046 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:40743047-40743559 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19084 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13770 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13769 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19085 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19086 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13771 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19087 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19088 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:40812395-40812894 Neighboring gene small G protein signaling modulator 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19089 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19090 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19092 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19091 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:40851734-40851957 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19093 Neighboring gene myocardin related transcription factor A Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:40867879-40868537 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:40894439-40894938 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:40906589-40907133 Neighboring gene MRTFA antisense RNA 1 Neighboring gene uncharacterized LOC105373037

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Molecular comparison of Neanderthal and Modern Human adenylosuccinate lyase. Van Laer B, et al. Sci Rep, 2018 Dec 20. PMID 30573755, Free PMC Article
  2. Inherent properties of adenylosuccinate lyase could explain S-Ado/SAICAr ratio due to homozygous R426H and R303C mutations. Ray SP, et al. Biochim Biophys Acta, 2013 Aug. PMID 23714113
  3. Structural and biochemical characterization of human adenylosuccinate lyase (ADSL) and the R303C ADSL deficiency-associated mutation. Ray SP, et al. Biochemistry, 2012 Aug 21. PMID 22812634, Free PMC Article
  4. Adenylosuccinate lyase deficiency in the United Kingdom pediatric population: first three cases. Lundy CT, et al. Pediatr Neurol, 2010 Nov. PMID 20933180
  5. Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations. Chen BC, et al. J Inherit Metab Dis, 2010 Dec. PMID 20177786

See all (97) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Electroclinical features and phenotypic differences in adenylosuccinate lyase deficiency: Long-term follow-up of seven patients from four families and appraisal of the literature.
    Title: Electroclinical features and phenotypic differences in adenylosuccinate lyase deficiency: Long-term follow-up of seven patients from four families and appraisal of the literature.
  2. Adenylosuccinate lyase (ADSL) is an EglN2 hydroxylase substrate in triple negative breast cancer.
    Title: Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer.
  3. ADSL undergoes conformational changes during catalysis which, together with the crystal structure of a hitherto undetermined product bound conformation, explains the molecular origin of disease for several modern human ADSL mutants.
    Title: Molecular comparison of Neanderthal and Modern Human adenylosuccinate lyase.
  4. involved in endometrial cancer aggressiveness by regulating expression of killer cell lectin-like receptor C3
    Title: Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate.
  5. Case Report: Malaysian patient compound heterozygous for two novel ADSL mutations giving rise to adenylosuccinate lyase deficiency.
    Title: Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations.
  6. Missense mutations in the adenylosuccinate lyase is associated with Adenylosuccinate lyase deficiency, an inborn error of purine metabolism characterized by neurological and physiological symptoms.
    Title: Inherent properties of adenylosuccinate lyase could explain S-Ado/SAICAr ratio due to homozygous R426H and R303C mutations.
  7. structural and biochemical characterization data of WT and mutant R303C ADSL by enzyme kinetics, product binding by isothermal titration calorimetry and X-ray crystallography to reveal the effects of the R303C mutation that results in a nonparallel reduction in enzyme activity
    Title: Structural and biochemical characterization of human adenylosuccinate lyase (ADSL) and the R303C ADSL deficiency-associated mutation.
  8. Results proved in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency that various mutations of ADSL destabilize to various degrees purinosome assembly and found that the ability to form purinosomes correlates with clinical phenotypes of individual ADSL patients.
    Title: Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency.
  9. D-ribose administration in Polish patients with adenylosuccinate lyase deficiency was accompanied by neither reduction in seizure frequency nor growth enhancement.
    Title: D-ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: absence of positive effect.
  10. the cases of the only three children diagnosed to date in the United Kingdom with adenylosuccinate lyase deficiency
    Title: Adenylosuccinate lyase deficiency in the United Kingdom pediatric population: first three cases.
Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

Go to the top of the page Help

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Adenylosuccinate lyase deficiency
MedGen: C0268126 OMIM: 103050 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.
EBI GWAS Catalog

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido) succinate lyase (fumarate-forming) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido) succinate lyase (fumarate-forming) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in 'de novo' AMP biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in 'de novo' AMP biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in 'de novo' IMP biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in 'de novo' XMP biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in AMP biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in AMP salvage IEA
Inferred from Electronic Annotation
more info
  
involved_in GMP biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in aerobic respiration IEA
Inferred from Electronic Annotation
more info
  
involved_in purine nucleotide biosynthetic process IC
Inferred by Curator
more info
 PubMed 
involved_in response to hypoxia IEA
Inferred from Electronic Annotation
more info
  
involved_in response to muscle activity IEA
Inferred from Electronic Annotation
more info
  
involved_in response to nutrient IEA
Inferred from Electronic Annotation
more info
  
involved_in response to starvation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

Go to the top of the page Help
Preferred Names
adenylosuccinate lyase
Names
adenylosuccinase
NP_000017.1
NP_001116850.1
NP_001304852.1
NP_001350769.1
NP_001397741.1
NP_001397743.1
NP_001397745.1
XP_016884125.1
XP_047297124.1
XP_054181166.1
XP_054181167.1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_007993.2 RefSeqGene

    Range
    5001..27868
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000026.4 → NP_000017.1  adenylosuccinate lyase isoform a

    See identical proteins and their annotated locations for NP_000017.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript and encodes the longest isoform (a).
    Source sequence(s)
    AF067853, AL022238, BG187609, BP298407
    Consensus CDS
    CCDS14001.1
    UniProtKB/Swiss-Prot
    B0QY76, O75495, P30566, Q5TI34
    UniProtKB/TrEMBL
    Q71UA4, X5D8S6
    Related
    ENSP00000485525.1, ENST00000623063.3
    Conserved Domains (1) summary
    cd03302
    Location:17 → 452
    Adenylsuccinate_lyase_2; Adenylsuccinate lyase (ASL)_subgroup 2

  2. NM_001123378.3 → NP_001116850.1  adenylosuccinate lyase isoform b

    See identical proteins and their annotated locations for NP_001116850.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks the penultimate, in-frame coding exon compared to variant 1. The resulting isoform (b) is shorter, missing an internal protein segment compared to isoform a.
    Source sequence(s)
    AF067854, AL022238, BG187609, BP298407
    Consensus CDS
    CCDS46714.1
    UniProtKB/TrEMBL
    A8K4X6
    Related
    ENSP00000341429.6, ENST00000342312.9
    Conserved Domains (1) summary
    cd03302
    Location:17 → 397
    Adenylsuccinate_lyase_2; Adenylsuccinate lyase (ASL)_subgroup 2

  3. NM_001317923.2 → NP_001304852.1  adenylosuccinate lyase isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate donor splice site at the 5' terminal exon, which results in translation initiation from an in-frame, downstream start codon compared to variant 1. The encoded isoform (c) has a shorter N-terminus compared to isoform a.
    Source sequence(s)
    AF067853, AL022238, BG187609, BP298407, KJ535056
    UniProtKB/TrEMBL
    Q71UA4
    Conserved Domains (1) summary
    cd03302
    Location:1 → 388
    Adenylsuccinate_lyase_2; Adenylsuccinate lyase (ASL)_subgroup 2

  4. NM_001363840.3 → NP_001350769.1  adenylosuccinate lyase isoform d

    Status: REVIEWED

    Source sequence(s)
    AL022238
    Consensus CDS
    CCDS87029.1
    UniProtKB/TrEMBL
    A0A1B0GTJ7, A0A1B0GWJ0
    Related
    ENSP00000490946.1, ENST00000636714.1
    Conserved Domains (1) summary
    cd03302
    Location:17 → 452
    Adenylsuccinate_lyase_2; Adenylsuccinate lyase (ASL)_subgroup 2

  5. NM_001410812.1 → NP_001397741.1  adenylosuccinate lyase isoform e

    Status: REVIEWED

    Source sequence(s)
    AL022238
    Consensus CDS
    CCDS93169.1
    UniProtKB/TrEMBL
    A0A7P0Z472
    Related
    ENSP00000505244.1, ENST00000680978.1

  6. NM_001410814.1 → NP_001397743.1  adenylosuccinate lyase isoform f

    Status: REVIEWED

    Source sequence(s)
    AL022238
    Consensus CDS
    CCDS93171.1
    UniProtKB/TrEMBL
    A0A7P0T8E4
    Related
    ENSP00000505155.1, ENST00000679723.1

  7. NM_001410816.1 → NP_001397745.1  adenylosuccinate lyase isoform g

    Status: REVIEWED

    Source sequence(s)
    AL022238
    Consensus CDS
    CCDS93170.1
    UniProtKB/TrEMBL
    A0A1B0GTG9
    Related
    ENSP00000489696.2, ENST00000637666.2

RNA

  1. NR_134256.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate donor splice site in the 3' region compared to variant 1. It is represented as non-coding because the use of the 5'-most translational start codon renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AF067853, AL022238, BG187609, BP298407, KJ535020

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_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    40346500..40387527
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017028636.2 → XP_016884125.1  adenylosuccinate lyase isoform X1

    UniProtKB/TrEMBL
    A0A1B0GTJ7
    Related
    ENSP00000216194.8, ENST00000216194.11

  2. XM_047441168.1 → XP_047297124.1  adenylosuccinate lyase isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    40817910..40858924
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054325191.1 → XP_054181166.1  adenylosuccinate lyase isoform X1

  2. XM_054325192.1 → XP_054181167.1  adenylosuccinate lyase isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P30566.2 GenPept UniProtKB/Swiss-Prot:P30566

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous