title: RAC2 Gene
<div class="infobox infobox-gene"> [@zhang2019]
| Gene Symbol | RAC2 | [@huang2020]Full Name | RAS-Related C3 Botulinum Toxin Substrate 2 |Chromosomal Location | 22q13.1 |NCBI Gene ID | [5879](https://www.ncbi.nlm.nih.gov/gene/5879) |OMIM | [602049](https://www.omim.org/entry/602049) |Ensembl ID | ENSG00000128340 |UniProt ID | [P15153](https://www.uniprot.org/uniprot/P15153) |Associated Diseases | Neutrophil Immunodeficiency Syndrome, Parkinson's Disease, Alzheimer's Disease |
</div>
Overview
flowchart TD
RAC2["RAC2"] -->|"associated with"| Ms["Ms"]
RAC2["RAC2"] -->|"associated with"| Atherosclerosis["Atherosclerosis"]
RAC2["RAC2"] -->|"regulates"| Ms["Ms"]
RAC2["RAC2"] -->|"regulates"| Autism["Autism"]
RAC2["RAC2"] -->|"associated with"| CTSD["CTSD"]
RAC2["RAC2"] -->|"associated with"| MAF["MAF"]
RAC2["RAC2"] -->|"interacts with"| CTSD["CTSD"]
RAC2["RAC2"] -->|"interacts with"| CDK4["CDK4"]
RAC2["RAC2"] -->|"interacts with"| CDKN1A["CDKN1A"]
RAC2["RAC2"] -->|"interacts with"| LCK["LCK"]
RAC2["RAC2"] -->|"associated with"| COL1A1["COL1A1"]
RAC2["RAC2"] -->|"interacts with"| Mapk["Mapk"]
RAC2["RAC2"] -->|"expressed in"| MIRNAS["MIRNAS"]
RAC2["RAC2"] -->|"associated with"| IBSP["IBSP"]
style RAC2 fill:#4fc3f7,stroke:#333,color:#000
...
title: RAC2 Gene
<div class="infobox infobox-gene"> [@zhang2019]
| Gene Symbol | RAC2 | [@huang2020]Full Name | RAS-Related C3 Botulinum Toxin Substrate 2 |Chromosomal Location | 22q13.1 |NCBI Gene ID | [5879](https://www.ncbi.nlm.nih.gov/gene/5879) |OMIM | [602049](https://www.omim.org/entry/602049) |Ensembl ID | ENSG00000128340 |UniProt ID | [P15153](https://www.uniprot.org/uniprot/P15153) |Associated Diseases | Neutrophil Immunodeficiency Syndrome, Parkinson's Disease, Alzheimer's Disease |
</div>
Overview
Mermaid diagram (expand to render)
RAS-Related C3 Botulinum Toxin Substrate 2 (RAC2) is a small GTPase belonging to the Rho family of GTP-binding proteins. Like other Rho GTPases, RAC2 cycles between an active GTP-bound state and an inactive GDP-bound state, functioning as a molecular switch that regulates diverse cellular processes.[@bosco2020] RAC2 is highly expressed in hematopoietic cells but also has significant expression in the nervous system, particularly in [neurons](/entities/neurons) and [microglia](/cell-types/microglia-neuroinflammation). It plays essential roles in actin cytoskeleton dynamics, synaptic plasticity, and immune cell function.[@huang2021]
In the brain, RAC2 is critically involved in regulating dendritic spine morphology and synaptic function. Through its effects on the actin cytoskeleton via the WASF (Wiskott-Aldrich syndrome protein family) complex, RAC2 influences filopodia and lamellipodia formation, which are fundamental to synaptic structure and plasticity.[@huang2021] Additionally, RAC2 regulates microglial chemotaxis and phagocytosis, linking it to neuroinflammatory processes in neurodegenerative diseases.[@marei2021] Dysregulated RAC2 signaling has been implicated in both Alzheimer's disease (AD) and Parkinson's disease (PD), where it contributes to synaptic deficits and chronic neuroinflammation.[@zhang2019][@huang2020]
Function RAC2 is a small GTPase belonging to the Rho family. It cycles between active (GTP-bound) and inactive (GDP-bound) states, acting as a molecular switch for various cellular processes.
Structure
~192 amino acids in length GTPase domain : Binds GTP/GDP and has intrinsic GTPase activityEffector region : Interacts with downstream targetsIsoprenylation site : For membrane localizationNormal Function in the Nervous System
Actin Cytoskeleton
Filopodia formation : Through WASF complexLamellipodia : Membrane ruffling and cell motilityDendritic spine morphology : Regulates synaptic structureSynaptic Function
Postsynaptic density : Regulates spine density and shapeSynaptic plasticity : Involved in [LTP](/mechanisms/long-term-potentiation) and LTD[NMDA receptor](/entities/nmda-receptor) trafficking : Modulates receptor localizationMicroglial Function
Chemotaxis and migration
Phagocytosis
[ROS](/entities/reactive-oxygen-species) production through NADPH oxidase activation
Disease Associations
Parkinson's Disease
RAC2 dysregulation in PD substantia nigra
Contributes to:
Microglial migration dysfunction
Altered phagocytosis
Neuroinflammation[@zhang2019]
Alzheimer's Disease
Altered RAC2 signaling in AD brain
Links to:
Actin cytoskeleton dysfunction
Synaptic spine abnormalities
Microglial pathology[@huang2020]
Neutrophil Immunodeficiency Syndrome
Rare immunodeficiency caused by RAC2 mutations
Defective neutrophil chemotaxis
Expression
Brain Expression
Neurons : High expression, especially in [cortex](/brain-regions/cortex) and [hippocampus](/brain-regions/hippocampus)Microglia : Moderate expression[Astrocytes](/entities/astrocytes) : Lower expressionTherapeutic Targeting
Inhibitors
EHT 1864 : RAC2-specific inhibitorNSC23766 : RAC1/2 inhibitorResearch Status
RAC2 as target is emerging area
Must balance neuronal vs. microglial effects[@marei2021]
See Also
[RAC2 Protein](/proteins/rac2-protein)
[Rho GTPases](/mechanisms/rho-gtpases)
[Actin Cytoskeleton](/mechanisms/actin-cytoskeleton)
[Synaptic Plasticity](/mechanisms/synaptic-plasticity)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[RAC1](/genes/rac1)
[CDC42](/genes/cdc42)
External Links
[NCBI Gene: RAC2](https://www.ncbi.nlm.nih.gov/gene/5879)
[UniProt: P15153](https://www.uniprot.org/uniprot/P15153)
[OMIM: 602049](https://www.omim.org/entry/602049)
[Ensembl: ENSG00000128340](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000128340)
[GeneCards: RAC2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=RAC2)
Brain Atlas Resources
[Allen Human Brain Atlas — RAC2 Expression](https://human.brain-map.org/microarray/search/show?search_term=RAC2): Gene expression data in human brain
[Allen Mouse Brain Atlas — RAC2](https://mouse.brain-map.org/search/show?search_term=RAC2): Mouse brain expression data
[BrainSpan — RAC2 Developmental Transcriptome](https://brainspan.org/lair/list?gene=RAC2): Developmental expression data
References
[Bosco, E.E. et al., RAC2 GTPase: An overview. Small GTPases (2020) (2020)](https://doi.org/10.1080/21541248.2020.1715389)
[Huang et al., RAC2 in neuronal function and dysfunction. Journal of Neuroscience Research (2021) (2021)](https://doi.org/10.1002/jnr.24789)
[Marei et al., Targeting RAC GTPases in CNS disorders. Pharmacology & Therapeutics (2021) (2021)](https://doi.org/10.1016/j.pharmthera.2021.107925)
[Zhang et al., RAC2 in Parkinson's disease neuroinflammation. Brain Pathology (2019) (2019)](https://doi.org/10.1111/bpa.12789)
[Huang et al., RAC2 dysfunction in Alzheimer's disease. Neurobiology of Aging (2020) (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.03.015)
Pathway Diagram The following diagram shows the key molecular relationships involving RAC2 — RAS-Related C3 Botulinum Toxin Substrate 2 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
Show full description