RGS4: Regulator of G Protein Signaling 4
A key modulator of G protein-coupled receptor signaling with roles in neuropsychiatric disorders and cancer
Gene Information Card
| Symbol | RGS4 |
|---|---|
| Full Name | Regulator of G Protein Signaling 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 5999 ncbi.nlm.nih.gov/gene/5999 |
| Ensembl ID | ENSG00000117152 |
| UniProt ID | P49798 |
| OMIM ID | 602516 |
| HGNC ID | 10000 |
| Aliases | RGS4, RGS4_HUMAN, MGC129626, MGC129627 |
Description
RGS4 (Regulator of G Protein Signaling 4) encodes a member of the regulator of G protein signaling (RGS) family. This protein functions as a GTPase-activating protein (GAP) for G alpha subunits of heterotrimeric G proteins, thereby negatively regulating G protein-coupled receptor (GPCR) signaling. RGS4 is highly expressed in the brain and heart and is implicated in neuropsychiatric disorders, cardiovascular function, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | RGS4 expression is altered in prefrontal cortex; polymorphisms associated with increased risk. | NCBI Gene, OMIM |
| Parkinson's disease | RGS4 modulates dopamine D2 receptor signaling; dysregulation contributes to motor symptoms. | NCBI Gene, OMIM |
| Breast cancer | RGS4 overexpression correlates with poor prognosis; promotes cell proliferation via GPCR signaling. | COSMIC, NCBI Gene |
| Cardiovascular disease | RGS4 regulates cardiac G protein signaling; implicated in heart failure and hypertension. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cortex) | 12.5 | High |
| Heart | 8.3 | Medium |
| Lung | 4.1 | Low |
| Liver | 2.0 | Low |
| Kidney | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HEK293 (embryonic kidney) | 7.8 | Common overexpression system |
| MCF7 (breast cancer) | 9.1 | High expression in breast cancer |
| HepG2 (liver cancer) | 2.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.136C>T (p.Arg46Cys) | Missense | 0.01% | Reduced GAP activity; associated with schizophrenia risk |
| c.385G>A (p.Gly129Ser) | Missense | 0.005% | Altered protein stability; reported in COSMIC |
| c.1-15C>T | Promoter | 0.02% | Associated with altered expression in brain |
Mutation functional classification
Loss of Function (LOF)
p.Arg46Cys reduces GTPase-activating activity, impairing negative regulation of GPCR signaling.
Gain of Function (GOF)
Not well documented; some variants may increase expression in cancer.
Dominant Negative (DN)
Not reported for RGS4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• GPCR downstream signaling (Reactome: R-HSA-388396)
• G alpha (i) signaling events (Reactome: R-HSA-418594)
• RGS regulation of G protein signaling (KEGG: hsa04020)
Protein Summary
RGS4 is a 23 kDa protein (205 amino acids) containing an RGS domain that binds to G alpha subunits and accelerates GTP hydrolysis, terminating GPCR signaling. It is predominantly cytosolic but can translocate to the plasma membrane upon activation. Post-translational modifications include palmitoylation, which regulates membrane localization. RGS4 is a key modulator of neuronal signaling, particularly in dopamine and glutamate pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RGS4 Knockout HEK293 Cell Line | EDJ-KQ3798 | Human | 5999 | Details Get a Quote |
| RGS4 Knockout HeLa Cell Line | EDJ-KQ54318 | Human | 5999 | Details Get a Quote |
| RGS4 Knockout A-549 Cell Line | EDJ-KQ62812 | Human | 5999 | Details Get a Quote |
| RGS4 Knockout HCT 116 Cell Line | EDJ-KQ71277 | Human | 5999 | Details Get a Quote |
