ADSLadenylosuccinate lyase
Autism Reports / Total Reports
3 / 9Rare Variants / Common Variants
10 / 0Chromosome Band
22q13.1Associated Disorders
ASDGenetic Category
Rare Single Gene Mutation, SyndromicRelevance 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.
External Links
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 | - | - | 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 | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.1129C>T | p.Leu377%3D | synonymous_variant | De novo | - | 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
1S
High Confidence, Syndromic
Score Delta: Score remained at 1S
criteria met
See SFARI Gene'scoring criteriaWe 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."
10/1/2019
S
1
Increased from S to 1
New Scoring Scheme
Description
Autism has been reported in a subset of individuals with adenylosuccinate lyase deficiency.
Reports Added
[New Scoring Scheme]1/1/2016
S
S
Increased from S to S
Description
Autism has been reported in a subset of individuals with adenylosuccinate lyase deficiency.
Reports Added
[Two novel mutant human adenylosuccinate lyases (ASLs) associated with autism and characterization of the equivalent mutant Bacillus subtilis ASL.2004] [A mutation in adenylosuccinate lyase associated with mental retardation and autistic features.1992] [An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids.1984] [Inhibition of defective adenylosuccinate lyase by HNE: a neurological disease that may be affected by oxidative stress.2006] [Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.2015]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:
http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser,
with the ability to view networks of associated ASD risk genes, can be found at
asd.princeton.edu.
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
exac.broadinstitute.org. 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:
ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle
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 www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
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.
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
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 |