GPR174 Gene - G Protein-Coupled Receptor 174 | Function, Mutations & Disease

GPR174 is a G protein-coupled receptor encoded by the GPR174 gene located on chromosome Xq21.1. It is a member of the rhodopsin-like GPCR family and is predominantly expressed in immune cells, including T cells, B cells, and natural killer cells. GPR174 has been implicated in the regulation of immune responses, particularly through its interaction with lysophosphatidylserine (LysoPS) as a ligand. It plays a role in T cell migration, cytokine production, and immune checkpoint modulation. Dysregulation of GPR174 is associated with autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, as well as certain cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• GPCR downstream signaling (Reactome: R-HSA-372790)

• Lysophosphatidylserine receptor signaling (Reactome: R-HSA-418594)

GPR174 is a 347-amino acid G protein-coupled receptor with seven transmembrane domains. It is activated by lysophosphatidylserine (LysoPS), a lipid mediator released during inflammation and cell death. Upon activation, GPR174 couples to Gαi/o proteins, leading to inhibition of adenylyl cyclase and modulation of downstream signaling pathways such as MAPK and PI3K/Akt. In immune cells, GPR174 regulates chemotaxis, cytokine secretion, and T cell differentiation. Its expression is enriched in lymphoid tissues and immune cell subsets, suggesting a role in adaptive immunity. Structural studies indicate that the extracellular loops and transmembrane helices are critical for ligand binding and receptor activation.