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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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RAC3
Rac family small GTPase 3
Chromosome 17 Β· 17q25.3
NCBI Gene: 5881Ensembl: ENSG00000169750.10HGNC: HGNC:9803UniProt: P60763
72PubMed Papers
21Diseases
0Drugs
11Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of cell adhesion mediated by integrinperinuclear region of cytoplasmneuronal cell bodyfilamentous actinneurodevelopmental disorder with structural brain anomalies and dysmorphic faciesIntellectual disabilityAbnormal brain morphologycomplex neurodevelopmental disorder
✦AI Summary

RAC3 is a small GTPase that plays critical roles in cytoskeletal organization, cell migration, and cancer progression. As a member of the Rac family, RAC3 cycles between active GTP-bound and inactive GDP-bound states to regulate cellular responses including actin-based protrusions and cell adhesion 1. Unlike the ubiquitously expressed Rac1, RAC3 has more restricted tissue distribution and appears late in vertebrate evolution, suggesting specialized functions 1. In cancer biology, RAC3 demonstrates oncogenic properties across multiple tumor types. In endometrial cancer, RAC3 overexpression correlates with poor prognosis, promotes cell proliferation and invasion through FASN upregulation, and is associated with DNA hypomethylation 2. Similarly, RAC3 drives breast cancer metastasis by enhancing invasive and motile phenotypes 3, while its silencing in lung cancer inhibits proliferation and induces apoptosis 4. RAC3 also maintains cancer stem cell properties in colorectal cancer through functional relationships with CFTR 5. The protein's expression is negatively correlated with immune cell infiltration in tumors, suggesting potential immunomodulatory effects 2. These findings establish RAC3 as both a critical regulator of cytoskeletal dynamics and a significant oncogenic driver across multiple cancer types.

Sources cited
1
RAC3 is a small GTPase with restricted tissue expression compared to Rac1 and appeared late in vertebrate evolution
PMID: 31514269
2
RAC3 overexpression in endometrial cancer correlates with poor prognosis, promotes proliferation/invasion via FASN, and is associated with DNA hypomethylation and reduced immune infiltration
PMID: 35917927
3
RAC3 activation correlates with metastatic potential and drives invasive/motile phenotypes in breast cancer
PMID: 16280046
4
RAC3 silencing in lung cancer inhibits proliferation and induces apoptosis
PMID: 25854406
5
RAC3 maintains cancer stem cell properties in colorectal cancer through functional relationship with CFTR
PMID: 33616840
Disease Associationsβ“˜21
neurodevelopmental disorder with structural brain anomalies and dysmorphic faciesOpen Targets
0.75Strong
Intellectual disabilityOpen Targets
0.42Moderate
Abnormal brain morphologyOpen Targets
0.42Moderate
complex neurodevelopmental disorderOpen Targets
0.37Weak
Distal shortening of limbsOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
lung adenocarcinomaOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
urinary bladder carcinomaOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
bladder transitional cell carcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
bladder tumorOpen Targets
0.07Suggestive
posterior cortical atrophyOpen Targets
0.04Suggestive
non-small cell lung carcinomaOpen Targets
0.04Suggestive
glioblastoma multiformeOpen Targets
0.04Suggestive
neuroblastomaOpen Targets
0.03Suggestive
atrial fibrillationOpen Targets
0.03Suggestive
Neurodevelopmental disorder with structural brain anomalies and dysmorphic faciesUniProt
Pathogenic Variants11
NM_005052.3(RAC3):c.348G>C (p.Lys116Asn)Pathogenic
RAC3-related disorder|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 116
NM_005052.3(RAC3):c.191A>G (p.Tyr64Cys)Likely pathogenic
Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies
β˜…β˜…β˜†β˜†2021β†’ Residue 64
NM_005052.3(RAC3):c.184G>A (p.Glu62Lys)Pathogenic
not provided|Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies|See cases
β˜…β˜…β˜†β˜†2021β†’ Residue 62
NM_005052.3(RAC3):c.86C>G (p.Pro29Arg)Likely pathogenic
Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies
β˜…β˜†β˜†β˜†2023β†’ Residue 29
NM_005052.3(RAC3):c.276T>A (p.Asn92Lys)Likely pathogenic
Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies
β˜…β˜†β˜†β˜†2022β†’ Residue 92
NM_005052.3(RAC3):c.187G>A (p.Asp63Asn)Likely pathogenic
not provided|Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies
β˜…β˜†β˜†β˜†2020β†’ Residue 63
NM_005052.3(RAC3):c.34G>C (p.Gly12Arg)Likely pathogenic
Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies
β˜…β˜†β˜†β˜†2019β†’ Residue 12
NM_005052.3(RAC3):c.193G>A (p.Asp65Asn)Likely pathogenic
RAC3-related disorder
β˜†β˜†β˜†β˜†2024β†’ Residue 65
NM_005052.3(RAC3):c.86C>T (p.Pro29Leu)Pathogenic
Abnormal brain morphology;Intellectual disability|Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies
β˜†β˜†β˜†β˜†2022β†’ Residue 29
NM_005052.3(RAC3):c.183GGA[1] (p.Glu62del)Pathogenic
Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies
β˜†β˜†β˜†β˜†2022β†’ Residue 62
NM_005052.3(RAC3):c.182A>T (p.Gln61Leu)Pathogenic
Abnormal brain morphology;Intellectual disability|Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies
β˜†β˜†β˜†β˜†2021β†’ Residue 61
View on ClinVar β†—
Related Genes
VAV1Protein interaction98%ABL1Protein interaction98%ABL2Protein interaction98%CTNND1Protein interaction98%CYBAProtein interaction98%DOCK2Protein interaction98%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
55%
Liver
50%
Ovary
13%
Lung
8%
Heart
5%
Gene Interaction Network
Click a node to explore
RAC3VAV1ABL1ABL2CTNND1CYBADOCK2
PROTEIN STRUCTURE
Preparing viewer…
PDB2QME Β· 1.75 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.73LoF Tolerant
pLIβ“˜
0.28Tolerant
Observed/Expected LoF0.42 [0.25–0.73]
RankingsWhere RAC3 stands among ~20K protein-coding genes
  • #6,579of 20,598
    Most Researched72
  • #2,763of 5,498
    Most Pathogenic Variants11
  • #5,628of 17,882
    Most Constrained (LOEUF)0.73
Genes detectedRAC3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
The androgen receptor is a tumor suppressor in estrogen receptor-positive breast cancer.
PMID: 33462444
Nat Med Β· 2021
1.00
2
Hypomethylated gene RAC3 induces cell proliferation and invasion by increasing FASN expression in endometrial cancer.
PMID: 35917927
Int J Biochem Cell Biol Β· 2022
0.90
3
The Rac3 GTPase in Neuronal Development, Neurodevelopmental Disorders, and Cancer.
PMID: 31514269
Cells Β· 2019
0.80
4
Deficiency of Nuclear Receptor Coactivator 3 Aggravates Diabetic Kidney Disease by Impairing Podocyte Autophagy.
PMID: 38483947
Adv Sci (Weinh) Β· 2024
0.70
5
Silencing of Rac3 inhibits proliferation and induces apoptosis of human lung cancer cells.
PMID: 25854406
Asian Pac J Cancer Prev Β· 2015
0.60