Target intelligence / Profile preview

Mas-related G protein-coupled receptor X4 (MRGPRX4)

Target: MRGPRX4
Molecular classification: G protein-coupled receptor, GPCR, Receptor, Class A (rhodopsin-like) GPCR, Delta subfamily GPCR

Overview

Mas-related G protein-coupled receptor X4 (MRGPRX4) is a Gq-coupled GPCR primarily expressed in small-diameter sensory neurons and skin keratinocytes. It is activated by bile acids and bilirubin, playing a key role in nonhistaminergic itch associated with cholestatic liver diseases. Recent development of selective agonists offers potential for anti-pruritic therapies. RAMP2 interaction reduces receptor signaling.

Other names: GPCRMRGX4SNSR6MAS related GPR family member X4

Mechanism of action

Gq-coupled GPCR activation leading to PLCβ stimulation and increased intracellular calcium levels.

Biological functions

Signal transductionSensory perception of itchPain transmission (proposed)Inflammation (proposed)Wound healing (proposed)Cellular responses via PLCβ and Ca2+ signaling

Disease associations

Cholestatic pruritusItchCancer progression (suggested)Liver diseases

Safety considerations

Off-target activation by some drugs can lead to pruritus or urticarial rash.Limited research on selective agonists/antagonists.

Interacting drugs

Bile acids

3 more in the full profile.

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