DRD2
protein-codingdopamine receptor D2, the group of Dopamine receptors|MicroRNA protein coding host genes
Gene summary
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. Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~66.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0020065
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Variants have been implicated in Myoclonic dystonia, though the data are mixed
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to DRD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000795.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 38 | 10 | 49 | ||
| missense | 67 | 5 | 1 | 73 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 68 | 43 | 11 | 122 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000786.1 | 7 | MANE Select | |
| Ensembl | ENSP00000354859.3 | 7 | MANE Select | |
| RefSeq | NP_001427297.1 | 7 | Standard | |
| RefSeq | NP_057658.2 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| drd2b | Danio rerio | Structure: whole organism Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Dopaminergic synapse - Homo sapiens (human)
- Gap junction - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Rap1 signaling pathway - Homo sapiens (human)
- Parkinson,s disease - Homo sapiens (human)
Biological Process
- temperature homeostasis
- response to hypoxia
- negative regulation of protein phosphorylation
- synaptic transmission, dopaminergic
- response to amphetamine
Molecular Function
- dopamine neurotransmitter receptor activity, coupled via Gi/Go
- adrenergic receptor activity
- protein binding
- drug binding
- dopamine binding
Cellular Component
- acrosomal vesicle
- plasma membrane
- integral component of plasma membrane
- postsynaptic density
- lateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000362072
- Coding exons
- 7
- Length
- 66096
- Individuals with no LoFs
- 125745
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125748
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.62 | 162 | 287 | 0.564 | 0.0000192 | 2928 |
| Missense (PolyPhen) | 32 | 93.379 | 0.34269 | 904 | ||
| Synonymous | -0.507 | 125 | 118 | 1.06 | 0.00000876 | 881 |
| Loss of Function | 3.23 | 3 | 17.7 | 0.170 | 0.00000102 | 184 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. {ECO:0000269|PubMed:21645528}.;
Recessive Scores
- pRec
- 0.724
Intolerance Scores
- LoFtool
- 0.305
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 18.06
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.770
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |