ADSL Gene

Name	adenylosuccinate lyase
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Adenylosuccinate lyase (ADSL) is a central enzyme in purine metabolism that catalyzes two non‐sequential reactions in the de novo synthesis of adenosine monophosphate (AMP): it converts succinylaminoimidazolecarboxamide ribotide (SAICAR) to aminoimidazolecarboxamide ribotide (AICAR) and adenylosuccinate (S‐AMP) to AMP (which also participates in the purine nucleotide cycle)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Its proper catalytic function is essential for maintaining cellular nucleotide pools that support energy metabolism, DNA/RNA synthesis, and cell proliferation. Consequently, mutations or dysregulation of ADSL can lead to profound neurometabolic disturbances. In patients, ADSL mutations are associated with a spectrum of clinical phenotypes—from severe neonatal encephalopathy with intractable seizures and psychomotor retardation to milder neurobehavioral impairments including autistic features."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its fundamental role in nucleotide synthesis, recent studies have uncovered oncogenic aspects of ADSL. In triple‐negative breast cancer cells, for instance, ADSL is post‐translationally modified by hydroxylation—specifically at proline 24—a modification that regulates the cellular levels of the oncogenic transcription factor cMYC via modulation of adenosine and fumarate production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In endometrial cancer, upregulation of ADSL has been linked to enhanced cell proliferation, migration, and invasiveness through the regulation of downstream effectors such as KLRC3 by fumarate production, suggesting that aberrant ADSL activity contributes to tumor aggressiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Biochemical and structural studies using model systems have shed light on the consequences of disease-associated mutations. Investigations in bacterial systems—where the Bacillus subtilis ADSL serves as a model for the human enzyme—demonstrate that even conservative substitutions (e.g. at residues corresponding to those found in human patients) can dramatically reduce enzymatic activity and stability without altering substrate affinity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, genetic analyses of affected families have revealed that both coding mutations and regulatory region changes (which reduce mRNA expression) can lead to markedly diminished enzyme activities, correlating with the severity of the clinical phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, evolutionary and structural comparisons have revealed that even subtle, human‐specific amino acid substitutions—located away from the active site—can modulate ADSL’s thermal stability and possibly its interaction with other proteins, without overtly affecting its catalytic kinetics; such findings underscore the enzyme’s sensitivity to conformational changes, which may contribute to neurodevelopmental disorders when perturbed."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ADSL functions as a critical catalyst in purine biosynthesis and nucleotide cycling. Disturbances in its function—either through genetic mutations that impair catalytic efficiency and structural integrity or via altered post‐translational modifications in the context of cancer—underscore its importance in both normal cellular metabolism and disease pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Agnieszka Jurecka, Marie Zikanova, Anna Tylki-Szymanska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical, biochemical and molecular findings in seven Polish patients with adenylosuccinate lyase deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2008.04.013"}], "href": "https://doi.org/10.1016/j.ymgme.2008.04.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18524658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18524658"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Katharina Mouchegh, Marie Zikánová, Georg F Hoffmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lethal fetal and early neonatal presentation of adenylosuccinate lyase deficiency: observation of 6 patients in 4 families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pediatr (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jpeds.2006.09.027"}], "href": "https://doi.org/10.1016/j.jpeds.2006.09.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17188615"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17188615"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "A M Marinaki, M Champion, M A Kurian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenylosuccinate lyase deficiency--first British case."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleosides Nucleotides Nucleic Acids (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1081/NCN-200027494"}], "href": "https://doi.org/10.1081/NCN-200027494"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15571235"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15571235"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Giada Zurlo, Xijuan Liu, Mamoru Takada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-13168-4"}], "href": "https://doi.org/10.1038/s41467-019-13168-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31729379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31729379"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Haengki Park, Kenji Ohshima, Satoshi Nojima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41374-017-0017-0"}], "href": "https://doi.org/10.1038/s41374-017-0017-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29467457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29467457"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sharmila Sivendran, David Patterson, Erin Spiegel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two novel mutant human adenylosuccinate lyases (ASLs) associated with autism and characterization of the equivalent mutant Bacillus subtilis ASL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M409974200"}], "href": "https://doi.org/10.1074/jbc.M409974200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15471876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15471876"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jennifer Brosius Palenchar, Roberta F Colman "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of a mutant Bacillus subtilis adenylosuccinate lyase equivalent to a mutant enzyme found in human adenylosuccinate lyase deficiency: asparagine 276 plays an important structural role."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi020640+"}], "href": "https://doi.org/10.1021/bi020640+"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12590570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12590570"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Claire T Lundy, Heinz Jungbluth, Keith R E Pohl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenylosuccinate lyase deficiency in the United Kingdom pediatric population: first three cases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Neurol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pediatrneurol.2010.06.007"}], "href": "https://doi.org/10.1016/j.pediatrneurol.2010.06.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20933180"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20933180"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "S Marie, V Race, M-C Nassogne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation of a nuclear respiratory factor 2 binding site in the 5' untranslated region of the ADSL gene in three patients with adenylosuccinate lyase deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/341036"}], "href": "https://doi.org/10.1086/341036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12016589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12016589"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Stephen P Ray, Michelle K Deaton, Glenn C Capodagli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and biochemical characterization of human adenylosuccinate lyase (ADSL) and the R303C ADSL deficiency-associated mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi300796y"}], "href": "https://doi.org/10.1021/bi300796y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22812634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22812634"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "A Jurecka, A Tylki-Szymanska, M Zikanova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "D-ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: absence of positive effect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10545-008-0904-z"}], "href": "https://doi.org/10.1007/s10545-008-0904-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18649008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18649008"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Bart Van Laer, Ulrike Kapp, Montserrat Soler-Lopez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular comparison of Neanderthal and Modern Human adenylosuccinate lyase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-36195-5"}], "href": "https://doi.org/10.1038/s41598-018-36195-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30573755"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30573755"}]}]}]}
Synonyms	ASASE, ASL, AMPS
Proteins	PUR8_HUMAN
NCBI Gene ID	158
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ADSL has 7,124 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 121 datasets.

Click the + buttons to view associations for ADSL from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ADSL Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by ADSL gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ADSL gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ADSL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ADSL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ADSL gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ADSL gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ADSL gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ADSL gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ADSL gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ADSL protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ADSL gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ADSL gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ADSL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ADSL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with ADSL gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ADSL gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ADSL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ADSL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ADSL protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ADSL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ADSL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ADSL gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ADSL gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ADSL gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ADSL protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ADSL gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ADSL gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ADSL gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ADSL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ADSL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with ADSL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ADSL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ADSL gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ADSL gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ADSL gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing ADSL from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ADSL gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ADSL gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ADSL gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ADSL gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.