GRK5 Gene - G Protein-Coupled Receptor Kinase 5 | Function, Mutations & Disease

GRK5 encodes a member of the G protein-coupled receptor kinase (GRK) subfamily of the Ser/Thr protein kinases. This kinase phosphorylates agonist-occupied G protein-coupled receptors (GPCRs), leading to receptor desensitization and internalization. GRK5 is widely expressed and plays critical roles in cardiac function, neuronal signaling, and immune regulation. Polymorphisms in GRK5 have been associated with altered cardiovascular risk and Alzheimer's disease susceptibility.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

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

• Beta-adrenergic receptor signaling (KEGG hsa04024)

• Class A/1 (Rhodopsin-like receptors) (Reactome R-HSA-373076)

GRK5 is a 590-amino acid serine/threonine kinase with an N-terminal regulator of G protein signaling (RGS) domain, a central kinase domain, and a C-terminal lipid-binding domain. It phosphorylates agonist-activated GPCRs, promoting arrestin binding and receptor desensitization. GRK5 is membrane-associated via palmitoylation and plays a key role in cardiac β-adrenergic receptor regulation, neuronal GPCR signaling, and immune cell chemotaxis. Altered expression or activity contributes to heart failure, hypertension, and Alzheimer's disease.