DRD2 Gene: Dopamine Receptor D2 - Function, Mutations, and Disease Associations

The DRD2 gene encodes the D2 subtype of the dopamine receptor, a G protein-coupled receptor (GPCR) that inhibits adenylyl cyclase activity. It is predominantly expressed in the brain, particularly in the striatum, and plays a critical role in motor control, reward, cognition, and endocrine function. DRD2 is a primary target for antipsychotic drugs and is implicated in schizophrenia, Parkinson disease, and substance use disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Dopaminergic synapse (KEGG: hsa04728)

• Neuroactive ligand-receptor interaction (KEGG: hsa04080)

• cAMP signaling pathway (KEGG: hsa04024)

• Cocaine addiction (KEGG: hsa05030)

• Alcoholism (KEGG: hsa05034)

The D2 dopamine receptor is a 443-amino acid protein with seven transmembrane domains typical of GPCRs. It exists as two splice variants: D2S (short) and D2L (long), differing in a 29-amino acid insert in the third intracellular loop. D2L is predominantly postsynaptic, while D2S acts as a presynaptic autoreceptor. The receptor couples to Gi/o proteins, inhibiting adenylyl cyclase and modulating ion channels. It is a major target for antipsychotic drugs (e.g., haloperidol, risperidone) and is involved in motor control, reward, and hormone regulation.