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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RGS2
regulator of G protein signaling 2
Chromosome 1 · 1q31.2
NCBI Gene: 5997Ensembl: ENSG00000116741.8HGNC: HGNC:9998UniProt: P41220
167PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
G-protein alpha-subunit bindingplasma membraneGTPase activator activityprotein bindingcataractspondylolisthesistrauma complicationneoplasm
✦AI Summary

RGS2 (regulator of G protein signaling 2) is a negative regulator of G protein-coupled receptor (GPCR) signaling that functions by increasing GTPase activity of G protein alpha subunits, driving them into their inactive GDP-bound form 1. The protein plays critical roles in cardiovascular regulation, with ZFP36-mediated destabilization of RGS2 mRNA leading to increased vascular smooth muscle contraction and elevated blood pressure 2. In immune contexts, RGS2 demonstrates complex regulatory functions. It can inhibit PD-L1 translation when coordinating with lncRNA HITT, thereby enhancing T cell-mediated cytotoxicity 3. However, RGS2 is also highly expressed in exhausted CD8+ T cells and is transcriptionally regulated by BATF2, where it promotes T cell exhaustion and tumor immune evasion by inhibiting CXCL13 secretion 4. Additionally, RGS2 shows differential expression patterns in neuropsychiatric conditions, being up-regulated in Brodmann Area 10 samples from schizophrenia patients 5. The protein's involvement extends to tissue repair functions, as it is among genes upregulated during macrophage activation by plasma extracellular vesicles, promoting anti-inflammatory responses and tissue remodeling 6. These diverse functions establish RGS2 as a crucial regulator across cardiovascular, immune, and neurological systems.

Sources cited
1
RGS2 increases GTPase activity of G protein alpha subunits, driving them into inactive GDP-bound form
PMID: 11063746
2
ZFP36-mediated destabilization of RGS2 mRNA affects vascular smooth muscle contraction and blood pressure
PMID: 39589932
3
RGS2 coordinates with lncRNA HITT to inhibit PD-L1 translation and enhance T cell cytotoxicity
PMID: 37014700
4
RGS2 is highly expressed in exhausted CD8+ T cells and regulated by BATF2, promoting T cell exhaustion
PMID: 40442751
5
RGS2 is up-regulated in Brodmann Area 10 samples from schizophrenia patients
PMID: 36443250
6
RGS2 is upregulated during macrophage activation by plasma extracellular vesicles, promoting tissue repair
PMID: 37272889
Disease Associationsⓘ20
cataractOpen Targets
0.27Weak
spondylolisthesisOpen Targets
0.26Weak
trauma complicationOpen Targets
0.26Weak
neoplasmOpen Targets
0.10Weak
breast cancerOpen Targets
0.10Suggestive
Alzheimer diseaseOpen Targets
0.08Suggestive
polyostotic fibrous dysplasiaOpen Targets
0.08Suggestive
type 2 diabetes mellitusOpen Targets
0.08Suggestive
Hypomaturation amelogenesis imperfectaOpen Targets
0.08Suggestive
Hypoplastic amelogenesis imperfectaOpen Targets
0.07Suggestive
pachyonychia congenitaOpen Targets
0.07Suggestive
ulnar-mammary syndromeOpen Targets
0.07Suggestive
bronchial diseaseOpen Targets
0.07Suggestive
amelogenesis imperfectaOpen Targets
0.06Suggestive
gastric cancerOpen Targets
0.06Suggestive
Huntington diseaseOpen Targets
0.06Suggestive
tooth agenesisOpen Targets
0.06Suggestive
cleft palateOpen Targets
0.05Suggestive
Moyamoya diseaseOpen Targets
0.05Suggestive
Fuchs endothelial corneal dystrophyOpen Targets
0.05Suggestive
Pathogenic Variants1
NM_002923.4(RGS2):c.274+1G>TLikely pathogenic
not provided
★☆☆☆2016
View on ClinVar ↗
Related Genes
PRKG1Protein interaction97%PRKG2Protein interaction91%GNAI3Protein interaction89%PPP1R9BProtein interaction88%GNA11Protein interaction85%GNA15Protein interaction85%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
21%
Lung
20%
Heart
6%
Liver
5%
Brain
4%
Gene Interaction Network
Click a node to explore
RGS2PRKG1PRKG2GNAI3PPP1R9BGNA11GNA15
PROTEIN STRUCTURE
Preparing viewer…
PDB2AF0 · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.10LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.74 [0.51–1.10]
RankingsWhere RGS2 stands among ~20K protein-coding genes
  • #2,675of 20,598
    Most Researched167 · top quartile
  • #4,759of 5,498
    Most Pathogenic Variants1
  • #11,240of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedRGS2
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Genetics of generalized anxiety disorder and related traits.
PMID: 28867940
Dialogues Clin Neurosci · 2017
1.00
2
Extracellular vesicles from human plasma dampen inflammation and promote tissue repair functions in macrophages.
PMID: 37272889
J Extracell Vesicles · 2023
0.90
3
Targeting BATF2-RGS2 axis reduces T-cell exhaustion and restores anti-tumor immunity.
PMID: 40442751
Mol Cancer · 2025
0.80
4
Systematic analysis of the RGS2 degron reveals characteristics of substrate recognition by the F-box protein FBXO44.
PMID: 40992661
J Biol Chem · 2025
0.72
5
Gene expression meta-analysis in patients with schizophrenia reveals up-regulation of RGS2 and RGS16 in Brodmann Area 10.
PMID: 36443250
Eur J Neurosci · 2023
0.70