Human Gene Module / Chromosome 5 / DRD1

DRD1Dopamine receptor D1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 4
Rare Variants / Common Variants
0 / 4
Aliases
DRD1, DADR,  DRD1A
Associated Syndromes
-
Chromosome Band
5q35.2
Associated Disorders
-
Relevance to Autism

A DRD1 haplotype was found to be associated with risk for autism spectrum disorders in male-only affected sib-pair families (Hettinger et al., 2008).

Molecular Function

This gene encodes the D1 subtype of the dopamine receptor, the most abundant dopamine receptor in the central nervous system. This G-protein coupled receptor stimulates adenylyl cyclase and activates cyclic AMP-dependent protein kinases. D1 receptors regulate neuronal growth and development, mediate some behavioral responses, and modulate dopamine receptor D2-mediated events

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
Rat
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DRD1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Support for association between ADHD and two candidate genes: NET1 and DRD1 Bobb AJ , et al. (2005) No -
2 Primary A DRD1 haplotype is associated with risk for autism spectrum disorders in male-only affected sib-pair families Hettinger JA , et al. (2008) Yes -
3 Support Associative learning and CA3-CA1 synaptic plasticity are impaired in D1R null, Drd1a-/- mice and in hippocampal siRNA silenced Drd1a mice Ortiz O , et al. (2010) No -
4 Support The role of the dopamine D1 receptor in social cognition: studies using a novel genetic rat model Homberg JR , et al. (2016) No -
Rare Variants  

No rare variants reported.

Common Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-48G>A - 5_prime_UTR_variant - - - 15717291 Bobb AJ , et al. (2005)
c.-684T>C 5'UTR 5_prime_UTR_variant - - - 15717291 Bobb AJ , et al. (2005)
c.-48G>A A/G 5_prime_UTR_variant - - - 18205172 Hettinger JA , et al. (2008)
c.-684T>C C/T 5_prime_UTR_variant - - - 18205172 Hettinger JA , et al. (2008)
SFARI Gene score
2

Strong Candidate

A DRD1 haplotype was found to be associated with risk for autism spectrum disorders in male-only affected sib-pair families (Hettinger et al., 2008). The two DRD1 SNPs that showed association with ASD in Hettinger et al., 2008 had previously been shown to associate with ADHD in Bobb et al., 2005. Associative learning and CA3-CA1 synaptic plasticity were shown to be impaired in three mouse models (D1R null, Drd1a-/- mice and in hippocampal siRNA silenced Drd1a mice) in Ortiz et al., 2010. Homberg et al., 2016 demonstrated that measures of social cognition (social interaction, scent marking, pup ultrasonic vocalizations and sociability) were strongly reduced in Drd1 mutant rats.

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

A DRD1 haplotype was found to be associated with risk for autism spectrum disorders in male-only affected sib-pair families (Hettinger et al., 2008). The two DRD1 SNPs that showed association with ASD in Hettinger et al., 2008 had previously been shown to associate with ADHD in Bobb et al., 2005. Associative learning and CA3-CA1 synaptic plasticity were shown to be impaired in three mouse models (D1R null, Drd1a-/- mice and in hippocampal siRNA silenced Drd1a mice) in Ortiz et al., 2010. Homberg et al., 2016 demonstrated that measures of social cognition (social interaction, scent marking, pup ultrasonic vocalizations and sociability) were strongly reduced in Drd1 mutant rats.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A DRD1 haplotype was found to be associated with risk for autism spectrum disorders in male-only affected sib-pair families (Hettinger et al., 2008). The two DRD1 SNPs that showed association with ASD in Hettinger et al., 2008 had previously been shown to associate with ADHD in Bobb et al., 2005. Associative learning and CA3-CA1 synaptic plasticity were shown to be impaired in three mouse models (D1R null, Drd1a-/- mice and in hippocampal siRNA silenced Drd1a mice) in Ortiz et al., 2010. Homberg et al., 2016 demonstrated that measures of social cognition (social interaction, scent marking, pup ultrasonic vocalizations and sociability) were strongly reduced in Drd1 mutant rats.

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

Increased from to 4

Description

A DRD1 haplotype was found to be associated with risk for autism spectrum disorders in male-only affected sib-pair families (Hettinger et al., 2008). The two DRD1 SNPs that showed association with ASD in Hettinger et al., 2008 had previously been shown to associate with ADHD in Bobb et al., 2005. Associative learning and CA3-CA1 synaptic plasticity were shown to be impaired in three mouse models (D1R null, Drd1a-/- mice and in hippocampal siRNA silenced Drd1a mice) in Ortiz et al., 2010. Homberg et al., 2016 demonstrated that measures of social cognition (social interaction, scent marking, pup ultrasonic vocalizations and sociability) were strongly reduced in Drd1 mutant rats.

Krishnan Probability Score

Score 0.57498613156642

Ranking 662/25841 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 0.89643154992401

Ranking 3253/18225 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 0.92623938531043

Ranking 10390/18665 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 380/461 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 0.40078423923998

Ranking 1449/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
GHSR growth hormone secretagogue receptor Human Protein Binding 2693 Q92847
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