Human Gene Module / Chromosome 11 / DRD2

DRD2Dopamine receptor D2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 7
Rare Variants / Common Variants
7 / 4
Aliases
DRD2, D2DR,  D2R
Associated Syndromes
Tourette syndrome
Chromosome Band
11q23.2
Associated Disorders
-
Relevance to Autism

Case-control and family-based association analysis of the DRD2 gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 253 controls revealed an increased frequency of the rs1800498 TT genotype in affected males compared to the comparison group (p=0.007) (Hettinger et al., 2012). Family-based assocation tests in the same report showed that the rs1800498 T allele was over-transmitted to affected males (p=0.0003) under an additive model.

Molecular Function

This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DRD2 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy Klassen T , et al. (2011) No -
2 Primary DRD2 and PPP1R1B (DARPP-32) polymorphisms independently confer increased risk for autism spectrum disorders and additively predict affected status in male-only affected sib-pair families Hettinger JA , et al. (2012) Yes -
3 Positive Association Language impairment and dyslexia genes influence language skills in children with autism spectrum disorders Eicher JD and Gruen JR (2014) Yes -
4 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
5 Positive Association De Novo Coding Variants Are Strongly Associated with Tourette Disorder Willsey AJ , et al. (2017) No -
6 Positive Association Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection Pardias AF , et al. (2018) No -
7 Support - Zhou X et al. (2022) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.412A>G p.Met138Val missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.448C>T p.Arg150Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1261G>A p.Val421Met missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1079G>A p.Arg360His missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.1228G>A p.Ala410Thr missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.1151G>A;c.1238G>A p.Trp384Ter;p.Trp413Ter stop_gained De novo - Simplex 28472652 Willsey AJ , et al. (2017)
c.152G>A p.Gly51Asp missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
G>A - intergenic_variant - - - 29483656 Pardias AF , et al. (2018)
- T/C 5KB_downstream_variant - - - 25448322 Eicher JD and Gruen JR (2014)
c.286-2730C>T;c.290-2737C>T - intron_variant - - - 22559203 Hettinger JA , et al. (2012)
c.-32+21324G>A;c.-32+21906G>A T/C intron_variant - - - 25448322 Eicher JD and Gruen JR (2014)
SFARI Gene score
2

Strong Candidate

Case-control and family-based association analysis of the DRD2 gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 253 controls revealed an increased frequency of the rs1800498 TT genotype in affected males compared to the comparison group (p=0.007) (Hettinger et al., 2012). Family-based assocation tests in the same report showed that the rs1800498 T allele was over-transmitted to affected males (p=0.0003) under an additive model. Two SNPs in the DRD2 gene showed suggestive evidence for association with performance on the Peabody Picture Vocabulary Test following meta-analysis of AGRE and SSC cohorts (Eicher and Gruen, 2015).

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

Case-control and family-based association analysis of the DRD2 gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 253 controls revealed an increased frequency of the rs1800498 TT genotype in affected males compared to the comparison group (p=0.007) (Hettinger et al., 2012). Family-based assocation tests in the same report showed that the rs1800498 T allele was over-transmitted to affected males (p=0.0003) under an additive model. Two SNPs in the DRD2 gene showed suggestive evidence for association with performance on the Peabody Picture Vocabulary Test following meta-analysis of AGRE and SSC cohorts (Eicher and Gruen, 2015).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Case-control and family-based association analysis of the DRD2 gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 253 controls revealed an increased frequency of the rs1800498 TT genotype in affected males compared to the comparison group (p=0.007) (Hettinger et al., 2012). Family-based assocation tests in the same report showed that the rs1800498 T allele was over-transmitted to affected males (p=0.0003) under an additive model. Two SNPs in the DRD2 gene showed suggestive evidence for association with performance on the Peabody Picture Vocabulary Test following meta-analysis of AGRE and SSC cohorts (Eicher and Gruen, 2015).

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

Case-control and family-based association analysis of the DRD2 gene in a cohort of 112 male-only affected sib-pair ASD families and a comparison cohort of 253 controls revealed an increased frequency of the rs1800498 TT genotype in affected males compared to the comparison group (p=0.007) (Hettinger et al., 2012). Family-based assocation tests in the same report showed that the rs1800498 T allele was over-transmitted to affected males (p=0.0003) under an additive model. Two SNPs in the DRD2 gene showed suggestive evidence for association with performance on the Peabody Picture Vocabulary Test following meta-analysis of AGRE and SSC cohorts (Eicher and Gruen, 2015).

Krishnan Probability Score

Score 0.50059349487112

Ranking 2071/25841 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 0.73326388867118

Ranking 4301/18225 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 0.93296102443011

Ranking 12130/18665 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 381/461 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 -0.13244557397093

Ranking 13572/20870 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
ARR3 arrestin 3, retinal (X-arrestin) Human Protein Binding 407 P36575
Clic6 chloride intracellular channel 6 Rat Protein Binding 304081 Q811Q2
COLEC12 collectin sub-family member 12 Human Protein Binding 81035 Q5KU26
DRD1 dopamine receptor D1 Human Protein Binding 1812 P21728
EPB41L1 erythrocyte membrane protein band 4.1-like 1 Human Protein Binding 2036 B7Z653
EPB41L2 erythrocyte membrane protein band 4.1-like 2 Human Protein Binding 2037 O43491
Gipc1 GIPC PDZ domain containing family, member 1 Rat Protein Binding 83823 Q9Z254
KCNJ6 potassium inwardly-rectifying channel, subfamily J, member 6 Human Protein Binding 3763 P48051
KLF11 Kruppel-like factor 11 Human DNA Binding 8462 B7ZAX4
NCS1 neuronal calcium sensor 1 Human Protein Binding 23413 E9PAY3
Nova1 neuro-oncological ventral antigen 1 Rat Protein Binding 298992 D4AAF8
SLC6A3 solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 Human Protein Binding 6531 Q01959
SSTR5 somatostatin receptor 5 Human Protein Binding 6755 P35346
TAAR1 trace amine-associated receptor 1 Human Protein Binding 134864 Q96RJ0
TRPC1 transient receptor potential cation channel, subfamily C, member 1 Human Protein Binding 7220 P48995
TRPC4 transient receptor potential cation channel, subfamily C, member 4 Human Protein Binding 7223 Q9UBN4
TRPC5 transient receptor potential cation channel, subfamily C, member 5 Human Protein Binding 7224 Q9UL62
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