Human Gene Module / Chromosome 22 / ADSL

ADSLadenylosuccinate lyase

SFARI Gene Score
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
3 / 9
Rare Variants / Common Variants
10 / 0
Limited Learn More
Associated Syndromes
Chromosome Band
Associated Disorders
Genetic Category
Rare Single Gene Mutation, Syndromic
Relevance to Autism

This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. Rare mutations in the ADSL gene have been found. For example, one study (Sivendran et al., 2004) found an autistic individual with two heterozygous ADSL mutations.

Molecular Function

The encoded protein mediates de novo synthesis of purines and formation of adenosine monophosphate from inosine monophosphate.

SFARI Genomic Platforms
Reports related to ADSL (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited A mutation in adenylosuccinate lyase associated with mental retardation and autistic features Stone RL , et al. (1992) No Autistic features
2 Primary Two novel mutant human adenylosuccinate lyases (ASLs) associated with autism and characterization of the equivalent mutant Bacillus subtilis ASL Sivendran S , et al. (2004) Yes -
3 Recent Recommendation Inhibition of defective adenylosuccinate lyase by HNE: a neurological disease that may be affected by oxidative stress Crif C , et al. (2006) No -
4 Support Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease Karaca E , et al. (2015) No -
5 Support Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice Tumien B , et al. (2017) No Developmental regression
6 Support - Mitani T et al. (2021) No Epilepsy/seizures
7 Support - Chen S et al. (2021) Yes DD, ID
8 Support - Zhou X et al. (2022) Yes -
9 Highly Cited An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids Jaeken J and Van den Berghe G (1984) No Autism, psychomotor delay
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.403-7C>T - splice_region_variant De novo NA - 35982159 Zhou X et al. (2022)
c.340T>C p.Tyr114His missense_variant Unknown - - 29286531 Tumien B , et al. (2017)
c.421C>T p.Arg141Trp missense_variant Unknown - - 29286531 Tumien B , et al. (2017)
c.675G>A p.Met225Ile missense_variant De novo NA Multiplex 35982159 Zhou X et al. (2022)
c.1129C>T p.Leu377%3D synonymous_variant De novo NA Simplex 35982159 Zhou X et al. (2022)
c.1153A>T p.Ile385Phe missense_variant Familial Both parents - 34800434 Chen S et al. (2021)
c.242A>C p.Glu81Ala missense_variant Familial Maternal - 15471876 Sivendran S , et al. (2004)
c.263T>G p.Val88Gly missense_variant Unknown Not maternal - 15471876 Sivendran S , et al. (2004)
c.1277G>A p.Arg426His missense_variant Familial Both parents Multiplex 34582790 Mitani T et al. (2021)
c.1288G>A p.Asp430Asn missense_variant Familial Both parents Multiplex 26539891 Karaca E , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score

High Confidence, Syndromic

Score Delta: Score remained at 1S


High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."


Increased from S to 1

New Scoring Scheme

Autism has been reported in a subset of individuals with adenylosuccinate lyase deficiency.

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.028242921270768

Ranking 25783/25841 scored genes

[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at
ExAC Score

Score 0.0002125753096645

Ranking 12684/18225 scored genes

[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.63254810050384

Ranking 825/18665 scored genes

[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see
Zhang D Score

Score 0.13481264399285

Ranking 5464/20870 scored genes

[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ALOX5 arachidonate 5-lipoxygenase Human Protein Binding 240 P09917
CALCOCO2 calcium binding and coiled-coil domain 2 Human Protein Binding 10241 Q13137
COMTD1 catechol-O-methyltransferase domain containing 1 Human Protein Binding 118881 Q86VU5
DDA1 DET1 and DDB1 associated 1 Human Protein Binding 79016 Q9BW61
GTF2E2 general transcription factor IIE, polypeptide 2, beta 34kDa Human Protein Binding 2961 P29084
GTF2I general transcription factor IIi Human Protein Binding 2969 P78347
KLHL20 kelch-like family member 20 Human Protein Binding 27252 Q9Y2M5
SNRNP27 small nuclear ribonucleoprotein 27kDa (U4/U6.U5) Human Protein Binding 11017 A8K513
TEKT2 Tektin-2 Human Protein Binding 27285 Q9UIF3
TEKT4 Tektin-4 Human Protein Binding 150483 Q8WW24
USP15 ubiquitin specific peptidase 15 Human Protein Binding 9958 Q9Y4E8
USP4 ubiquitin specific peptidase 4 (proto-oncogene) Human Protein Binding 7375 Q13107
USP47 ubiquitin specific peptidase 47 Human Protein Binding 55031 Q96K76
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