DRD2

HIGH

Dopamine receptor D2

Chromosome: 11q23.2

Gene Overview

DRD2 encodes the dopamine D2 receptor, a G protein-coupled receptor that inhibits adenylyl cyclase and modulates dopaminergic signaling in striatum, cortex, and limbic regions. DRD2 is the primary target of antipsychotic drugs; allelic variation influences treatment response and side effects. GWAS have implicated DRD2 and nearby ANKK1 (rs1800497) in schizophrenia, addiction, and Parkinson disease. The receptor exists in long (D2L) and short (D2S) splice variants with distinct signaling properties. Expression is highest in striatum, substantia nigra, and pituitary. DRD2 antagonism underlies antipsychotic efficacy but also causes extrapyramidal and metabolic side effects.

Molecular Function

  • dopamine binding
  • G protein-coupled receptor activity
  • adenylyl cyclase inhibition
  • neurotransmitter signaling

Protein class: dopamine receptor

Regulatory Annotation

Promoter activity: Tissue-specific promoters for neuronal vs pituitary expression.

Enhancer associations: Schizophrenia-associated variants affect DRD2 expression in striatal neurons.

Methylation sensitivity: DRD2 promoter methylation correlates with antipsychotic response.

eQTL tissues: brain, striatum

Tissue Expression Context

brainTPM range: 5-25GTEx vv8
pituitaryTPM range: 20-60GTEx vv8

Pathways

Linked Diseases & Exposures

Diseases

Exposures

Mechanistic Hypotheses

Reduced DRD2 signaling in striatum contributes to positive symptoms of schizophrenia; antipsychotics restore dopamine balance via D2 antagonism; genetic variants influence receptor density and drug response.

D2 occupancy by antipsychotics correlates with clinical response; DRD2 polymorphisms affect binding affinity.

HIGH

Confidence Rating

Overall evidence confidence for this gene entry: HIGH

References

  1. 1.Ritchie T, Noble EP (2003). Dopamine D2 receptor gene (DRD2) and its association with striatal dopamine binding. American Journal of Medical Genetics. doi:10.1002/ajmg.b.10019
  2. 2.GTEx Consortium (2020). GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science. doi:10.1126/science.aaz1776
  3. 3.Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature. doi:10.1038/nature13595