Human Gene Module / Chromosome 3 / DRD3

DRD3dopamine receptor D3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 9
Rare Variants / Common Variants
4 / 2
Aliases
DRD3, D3DR,  ETM1,  FET1,  MGC149204,  MGC149205,  DRD3
Associated Syndromes
-
Chromosome Band
3q13.31
Associated Disorders
ADHD
Relevance to Autism

Genetic association has been found between the DRD3 gene and autism in the Dutch and UK populations (de Krom et al., 2009).

Molecular Function

This gene encodes the D3 subtype of dopamine receptor

SFARI Genomic Platforms
Reports related to DRD3 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization Guillin O , et al. (2001) No -
2 Highly Cited Association between schizophrenia and homozygosity at the dopamine D3 receptor gene Crocq MA , et al. (1992) No -
3 Recent Recommendation Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement Dalley JW , et al. (2007) No -
4 Recent Recommendation Dopamine receptor-mediated regulation of neuronal "clock" gene expression Imbesi M , et al. (2008) No -
5 Primary A common variant in DRD3 receptor is associated with autism spectrum disorder de Krom M , et al. (2008) Yes ADHD
6 Support Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy Klassen T , et al. (2011) No -
7 Positive Association DRD3 gene and striatum in autism spectrum disorder Staal WG , et al. (2015) Yes Striatal volume
8 Support - Zhou X et al. (2022) Yes -
9 Highly Cited Dopamine D3 receptor mutant mice exhibit increased behavioral sensitivity to concurrent stimulation of D1 and D2 receptors Xu M , et al. (1997) No -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.477A>G p.Val159%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.150G>A p.Val50%3D synonymous_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.448G>A p.Val150Met missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.987A>G p.Gln329= synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.383+2327C>T - intron_variant - - - 25792691 Staal WG , et al. (2015)
c.383+2327C>T - intron_variant - - - 19058789 de Krom M , et al. (2008)
SFARI Gene score
2

Strong Candidate

A single unreplicated association was reported (de Krom et al., 2009; PMID: 19058789).

Score Delta: Score remained at 2

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
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2

Decreased from 3 to 2

Description

A single unreplicated association was reported (de Krom et al., 2009; PMID: 19058789).

10/1/2019
4
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3

Decreased from 4 to 3

New Scoring Scheme
Description

A single unreplicated association was reported (de Krom et al., 2009; PMID: 19058789).

Reports Added
[New Scoring Scheme]
4/1/2015
4
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4

Decreased from 4 to 4

Description

A single unreplicated association was reported (de Krom et al., 2009; PMID: 19058789).

7/1/2014
No data
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4

Increased from No data to 4

Description

A single unreplicated association was reported (de Krom et al., 2009; PMID: 19058789).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A single unreplicated association was reported (de Krom et al., 2009; PMID: 19058789).

Krishnan Probability Score

Score 0.49589508925368

Ranking 2757/25841 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 0.01029534331533

Ranking 9981/18225 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 0.83031989018829

Ranking 2859/18665 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).
Larsen Cumulative Evidence Score

Score 1

Ranking 420/461 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.
Zhang D Score

Score -0.1237892442442

Ranking 13268/20870 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.
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