DRD5 Gene: Dopamine Receptor D5 - Function, Mutations, and Disease Associations

The DRD5 gene encodes the dopamine receptor D5, a G protein-coupled receptor (GPCR) that belongs to the D1-like dopamine receptor family. It is primarily expressed in the brain, kidney, and peripheral tissues. DRD5 mediates dopaminergic signaling via activation of adenylyl cyclase and cAMP production. It plays roles in cognitive function, blood pressure regulation, and immune modulation. Genetic variants in DRD5 have been associated with schizophrenia, attention-deficit/hyperactivity disorder (ADHD), essential hypertension, and certain cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Dopamine D1 receptor signaling pathway (Reactome R-HSA-389930)

• GPCR downstream signaling (Reactome R-HSA-388396)

• cAMP signaling pathway (KEGG hsa04024)

• Neuroactive ligand-receptor interaction (KEGG hsa04080)

The dopamine D5 receptor (UniProt P21918) is a 477-amino acid GPCR with seven transmembrane domains. It shares high homology with the D1 receptor but has a 10-fold higher affinity for dopamine. D5 is coupled to Gs alpha, stimulating adenylyl cyclase and increasing intracellular cAMP. It is expressed in neurons, renal tubules, and immune cells. The receptor modulates synaptic plasticity, blood pressure via natriuresis, and cytokine release. Post-translational modifications include N-glycosylation and palmitoylation. Structural studies reveal a ligand-binding pocket distinct from D1, enabling selective pharmacology.