RGS14 Gene - Regulator of G Protein Signaling 14 | Function, Mutations & Disease

RGS14 (Regulator of G Protein Signaling 14) is a protein-coding gene located on chromosome 5q35.3. It encodes a 547-amino acid protein that functions as a GTPase-activating protein (GAP) for Gαi/o subunits, thereby attenuating G protein-coupled receptor (GPCR) signaling. RGS14 also contains a GoLoco motif that binds Gαi-GDP, and two Ras-binding domains (RBDs) that link to Ras/MAPK pathways. The protein is highly expressed in the brain, particularly in hippocampal CA2 neurons, where it regulates synaptic plasticity, spatial learning, and memory. RGS14 has been implicated in cancer, neurological disorders, and cardiovascular function.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• GPCR signaling (RGS family)

• Ras/MAPK signaling

• Gαi/o signaling cascade

• Synaptic plasticity (hippocampal CA2)

RGS14 is a 547-amino acid protein (UniProt O43566) that contains an N-terminal RGS domain (GAP activity for Gαi/o), a central GoLoco motif (binds Gαi-GDP), and two C-terminal Ras-binding domains (RBD1 and RBD2). It localizes to the cytoplasm and nucleus, and in neurons it is enriched at postsynaptic densities. RGS14 integrates GPCR and Ras signaling, modulating synaptic plasticity, long-term potentiation (LTP), and spatial memory. In cancer, altered RGS14 expression or mutation can disrupt these pathways, contributing to tumor progression.