Human Gene Module / Chromosome 20 / ADA

ADAadenosine deaminase

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 8
Rare Variants / Common Variants
3 / 3
Aliases
-
Associated Syndromes
-
Chromosome Band
20q13.12
Associated Disorders
-
Relevance to Autism

Several studies have found a genetic association between the ADA gene and autism. Positive associations have been found in Italian and North American population samples.

Molecular Function

The encoded protein catalyzes the hydrolysis of adenosine to inosine.

External Links
Gene CardPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser
Reports related to ADA (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Positive Association Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies Persico AM , et al. (2000) Yes -
2 Primary Autism: evidence of association with adenosine deaminase genetic polymorphism Bottini N , et al. (2001) Yes -
3 Recent Recommendation Partially adenosine deaminase-deficient mice develop pulmonary fibrosis in association with adenosine elevations Chunn JL , et al. (2005) No -
4 Positive Association The G22A polymorphism of the ADA gene and susceptibility to autism spectrum disorders Hettinger JA , et al. (2007) Yes -
5 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
7 Support - Zhou X et al. (2022) Yes -
8 Highly Cited Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity Giblett ER , et al. (1972) No -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.845_845+1del - splice_site_variant De novo - - 35982159 Zhou X et al. (2022)
c.528C>T p.Thr176= synonymous_variant De novo - Simplex 28714951 Lim ET , et al. (2017)
c.370_372del p.Leu124del frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.22G>A p.Asp8Asn missense_variant - - - 11354825 Bottini N , et al. (2001)
c.22G>A p.Asp8Asn missense_variant - - - 11121182 Persico AM , et al. (2000)
c.22G>A p.Asp8Asn missense_variant - - - 17340203 Hettinger JA , et al. (2007)
SFARI Gene score
2

Strong Candidate

There are multiple, but inconsistent, associations of the functional p.Asp8Asn SNP in 3 studies (all fewer than 150 families/cases; Persico et al., 2000 PMID: 11121182; Bottini et al., 2001 PMID: 11354825; Hettinger et al., 2008 PMID: 17340203), which places the gene in category 4. One early report of reduced enzymatic activity in sera from individuals with ASD boosts it to category 3.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

There are multiple, but inconsistent, associations of the functional p.Asp8Asn SNP in 3 studies (all fewer than 150 families/cases; Persico et al., 2000 PMID: 11121182; Bottini et al., 2001 PMID: 11354825; Hettinger et al., 2008 PMID: 17340203), which places the gene in category 4. One early report of reduced enzymatic activity in sera from individuals with ASD boosts it to category 3.

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

There are multiple, but inconsistent, associations of the functional p.Asp8Asn SNP in 3 studies (all fewer than 150 families/cases; Persico et al., 2000 PMID: 11121182; Bottini et al., 2001 PMID: 11354825; Hettinger et al., 2008 PMID: 17340203), which places the gene in category 4. One early report of reduced enzymatic activity in sera from individuals with ASD boosts it to category 3.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2017
3
icon
3

Decreased from 3 to 3

Description

There are multiple, but inconsistent, associations of the functional p.Asp8Asn SNP in 3 studies (all fewer than 150 families/cases; Persico et al., 2000 PMID: 11121182; Bottini et al., 2001 PMID: 11354825; Hettinger et al., 2008 PMID: 17340203), which places the gene in category 4. One early report of reduced enzymatic activity in sera from individuals with ASD boosts it to category 3.

Reports Added
[Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.2017]
7/1/2014
No data
icon
3

Increased from No data to 3

Description

There are multiple, but inconsistent, associations of the functional Asp8Asn SNP in 3 studies (all fewer than 150 families/cases; Persico et al., 2000 PMID: 11121182; Bottini et al., 2001 PMID: 11354825; Hettinger et al., 2008 PMID: 17340203), which places the gene in category 4. One early report of reduced enzymatic activity in sera from individuals with ASD boosts it to category 3.

4/1/2014
No data
icon
3

Increased from No data to 3

Description

There are multiple, but inconsistent, associations of the functional Asp8Asn SNP in 3 studies (all fewer than 150 families/cases; Persico et al., 2000 PMID: 11121182; Bottini et al., 2001 PMID: 11354825; Hettinger et al., 2008 PMID: 17340203), which places the gene in category 4. One early report of reduced enzymatic activity in sera from individuals with ASD boosts it to category 3.

Krishnan Probability Score

Score 0.35869684196302

Ranking 24175/25841 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.
Original Source
ExAC Score

Score 2.8329852798177E-9

Ranking 16428/18225 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
Original Source
Sanders TADA Score

Score 0.93535434410184

Ranking 12851/18665 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).
Original Source
Larsen Cumulative Evidence Score

Score 22.5

Ranking 88/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score -0.28194348412026

Ranking 16923/20870 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.
Original Source
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ACTBL2 actin, beta-like 2 Human Protein Binding 345651 Q562R1
ADORA1 adenosine A1 receptor Golden hamster Protein Binding N/A N/A
ADORA2B adenosine A2b receptor Human Protein Binding 136 P29275
CDX1 caudal type homeobox 1 Mouse DNA Binding 12590 P18111
CDX2 caudal type homeobox 2 Mouse DNA Binding 12591 P43241
DPP4 dipeptidyl-peptidase 4 Human Protein Binding 1803 P27487
EHMT1 G9a Fruit Fly Direct Regulation 30971 Q95RU8
GATA4 GATA binding protein 4 Mouse DNA Binding 14463 Q08369
GRB2 growth factor receptor-bound protein 2 Human Protein Binding 2885 P62993
NFIC nuclear factor I/C Mouse DNA Binding 18029 P70255
PDX1 pancreatic and duodenal homeobox 1 Mouse DNA Binding 18609 P52946
POTEF POTE ankyrin domain family member F Human Protein Binding 728378 A5A3E0
YY1 YY1 transcription factor Mouse DNA Binding 22632 Q00899
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