Human Gene Module / Chromosome 22 / ADORA2A

ADORA2Aadenosine A2a receptor

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 7
Rare Variants / Common Variants
0 / 2
Aliases
ADORA2A, RDC8,  hA2aR,  ADORA2
Associated Syndromes
-
Chromosome Band
22q11.23
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the ADORA2A gene and autism in a Caucasian sample (Freitag et al., 2010).

Molecular Function

The encoded protein is a receptor subtypes for adenosine

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ADORA2A (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Recent Recommendation Adenosine A2A receptors are essential for long-term potentiation of NMDA-EPSCs at hippocampal mossy fiber synapses Rebola N , et al. (2008) No -
2 Recent Recommendation The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist Jaakola VP , et al. (2008) No -
3 Recent Recommendation FGF acts as a co-transmitter through adenosine A(2A) receptor to regulate synaptic plasticity Flajolet M , et al. (2008) No -
4 Recent Recommendation The A2A adenosine receptor rescues the urea cycle deficiency of Huntington's disease by enhancing the activity of the ubiquitin-proteasome system Chiang MC , et al. (2009) No -
5 Primary Adenosine A(2A) receptor gene (ADORA2A) variants may increase autistic symptoms and anxiety in autism spectrum disorder Freitag CM , et al. (2009) Yes 22q11.2 deletion syndrome
6 Highly Cited Evidence for functionally important adenosine A2a receptors in the rat hippocampus Cunha RA , et al. (1994) No -
7 Highly Cited Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor Ledent C , et al. (1997) No -
Rare Variants  

No rare variants reported.

Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-275+1797C>T;c.-275+1817C>T;c.-274-3588C>T C to T intron_variant - - - 19565319 Freitag CM , et al. (2009)
c.333-527T>C C to T intron_variant - - - 19565319 Freitag CM , et al. (2009)
SFARI Gene score
2

Strong Candidate

There is one published gene-based association study that suggests ADORA2A may be involved in autism. In this study, Freitag and colleagues (2010) genotyped eight SNPs in 98 ASD patients and 234 controls. They found nominal association of 2 SNPS, but the study was not well powered and there has been no independent replication of this finding.

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

There is one published gene-based association study that suggests ADORA2A may be involved in autism. In this study, Freitag and colleagues (2010) genotyped eight SNPs in 98 ASD patients and 234 controls. They found nominal association of 2 SNPS, but the study was not well powered and there has been no independent replication of this finding.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

There is one published gene-based association study that suggests ADORA2A may be involved in autism. In this study, Freitag and colleagues (2010) genotyped eight SNPs in 98 ASD patients and 234 controls. They found nominal association of 2 SNPS, but the study was not well powered and there has been no independent replication of this finding.

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

There is one published gene-based association study that suggests ADORA2A may be involved in autism. In this study, Freitag and colleagues (2010) genotyped eight SNPs in 98 ASD patients and 234 controls. They found nominal association of 2 SNPS, but the study was not well powered and there has been no independent replication of this finding.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

There is one published gene-based association study that suggests ADORA2A may be involved in autism. In this study, Freitag and colleagues (2010) genotyped eight SNPs in 98 ASD patients and 234 controls. They found nominal association of 2 SNPS, but the study was not well powered and there has been no independent replication of this finding.

Krishnan Probability Score

Score 0.45906107556026

Ranking 9605/25841 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 0.33162435622767

Ranking 6337/18225 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 0.93092613106796

Ranking 11560/18665 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 2

Ranking 373/461 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 0.066643801557498

Ranking 6829/20870 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
ACTN1 actinin, alpha 1 Human Protein Binding 87 P12814
ACTN2 actinin alpha 2 Mouse Protein Binding 11472 Q9JI91
ACTN4 actinin alpha 4 Mouse Protein Binding 60595 P57780
CREB1 cAMP responsive element binding protein 1 Rat DNA Binding 81646 P15337
CREBBP CREB binding protein Rat DNA Binding 54244 Q6JHU9
CYTH2 cytohesin 2 Human Protein Binding 9266 Q99418
DRD2 dopamine receptor D2 Human Protein Binding 1813 P14416
GRM5 glutamate receptor, metabotropic 5 Rat Protein Binding 24418 P31424
MECP2 methyl CpG binding protein 2 (Rett syndrome) Human DNA Binding 4204 P51608
mGluR5 glutamate receptor, metabotropic 5 Rat Protein Binding 24418 P31424
ZNF148 zinc finger protein 148 Human DNA Binding 7707 Q9UQR1
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