DRD4: Dopamine Receptor D4
A G protein-coupled receptor implicated in neuropsychiatric disorders and behavioral traits
Gene Information Card
| Symbol | DRD4 |
|---|---|
| Full Name | Dopamine Receptor D4 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 1815 ncbi.nlm.nih.gov/gene/1815 |
| Ensembl ID | ENSG00000159596 |
| UniProt ID | P21917 |
| OMIM ID | 126452 |
| HGNC ID | 3025 |
| Aliases | D4DR, D4R, DRD4.7 |
Description
The DRD4 gene encodes the D4 subtype of the dopamine receptor, a G protein-coupled receptor (GPCR) that inhibits adenylyl cyclase upon dopamine binding. It is highly expressed in the prefrontal cortex, hippocampus, and amygdala, and is involved in neurotransmission, cognition, and reward pathways. Polymorphic variations, particularly a 48-bp VNTR in exon 3, are associated with altered receptor function and have been linked to attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and novelty-seeking behavior.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Attention-Deficit/Hyperactivity Disorder (ADHD) | The 7-repeat allele of the 48-bp VNTR in exon 3 is associated with reduced receptor function and altered dopaminergic signaling in prefrontal cortex, contributing to inattention and hyperactivity. | Multiple case-control and meta-analyses (e.g., Faraone et al., 2005; Li et al., 2006) show significant association. |
| Schizophrenia | DRD4 polymorphisms may modulate dopamine signaling in mesolimbic pathways; some studies report association with negative symptoms and treatment response. | Genetic association studies and pharmacogenetic analyses (e.g., Serretti et al., 2001; Hwang et al., 2012). |
| Novelty Seeking Personality Trait | The 7-repeat allele is linked to higher novelty seeking scores, possibly due to altered D4 receptor density in limbic regions. | Twin and candidate gene studies (e.g., Ebstein et al., 1996; Benjamin et al., 1996). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Prefrontal Cortex | 12.5 | Medium |
| Hippocampus | 8.3 | Low |
| Amygdala | 7.1 | Low |
| Caudate Nucleus | 5.2 | Low |
| Cerebellum | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.0 | Neuronal model |
| SK-N-SH (neuroblastoma) | 12.4 | Neuronal model |
| HEK293 (embryonic kidney) | 0.5 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| 48-bp VNTR (exon 3) | VNTR | Common (allele frequencies vary by population) | Alters receptor length and signaling; 7-repeat allele associated with reduced cAMP inhibition. |
| -521 C/T (rs1800955) | SNP | Common (MAF ~0.4) | Promoter variant affecting transcription; T allele linked to lower DRD4 expression. |
| Val194Gly (rs1800443) | Missense | Rare | May alter receptor conformation and ligand binding. |
Mutation functional classification
Loss of Function (LOF)
The 7-repeat VNTR allele results in a longer third intracellular loop, leading to reduced G protein coupling and blunted cAMP inhibition.
Gain of Function (GOF)
Not well documented; some rare variants may increase receptor sensitivity, but evidence is limited.
Dominant Negative (DN)
Not reported for DRD4.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity (GO:0004930) | • dopamine neurotransmitter receptor activity (GO:0004952) |
| • adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193) | • dopaminergic (GO:0001963) |
| • plasma membrane (GO:0005886) |
Pathways
• Dopamine receptor signaling pathway (KEGG: hsa04728)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
• cAMP signaling pathway (KEGG: hsa04024)
Protein Summary
The dopamine D4 receptor is a 387-amino acid (common variant) GPCR with seven transmembrane domains. It is primarily expressed in the brain, especially in regions involved in cognition and emotion. The receptor couples to Gi/Go proteins, inhibiting adenylyl cyclase and reducing cAMP levels. Its most notable feature is a highly polymorphic 48-bp VNTR in exon 3, which codes for a variable number of proline-rich repeats in the third intracellular loop, affecting receptor function and drug binding. DRD4 is a target for antipsychotic drugs (e.g., clozapine) and is implicated in neuropsychiatric disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DRD4 Knockout HEK293 Cell Line | EDJ-KQ2237 | Human | 1815 | Details Get a Quote |
| DRD4 Knockout HeLa Cell Line | EDJ-KQ53116 | Human | 1815 | Details Get a Quote |
| DRD4 Knockout A-549 Cell Line | EDJ-KQ61589 | Human | 1815 | Details Get a Quote |
| DRD4 Knockout HCT 116 Cell Line | EDJ-KQ70079 | Human | 1815 | Details Get a Quote |
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