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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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RAC1
Rac family small GTPase 1
Chromosome 7 Β· 7p22.1
NCBI Gene: 5879Ensembl: ENSG00000136238.21HGNC: HGNC:9801UniProt: A4D2P0
1,340PubMed Papers
21Diseases
0Drugs
25Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly Studied
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein kinase bindingruffle assemblypositive regulation of neutrophil chemotaxishepatocyte growth factor receptor signaling pathwayintellectual disability, autosomal dominant 48melanomaAbnormality of the skeletal systemcutaneous melanoma
✦AI Summary

RAC1 is a small GTPase that functions as a molecular switch regulating actin cytoskeleton dynamics and cell motility. As a GTP-binding protein, RAC1 cycles between inactive GDP-bound and active GTP-bound states, with its activity modulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins 1. RAC1 controls lamellipodium assembly and focal adhesion dynamics, enabling cell migration and invasion 2. In epithelial tissues, RAC1 regulates cytoskeletal rearrangement critical for physiological cell shedding and barrier integrity; impaired RAC1 function causes cell overcrowding, tight junction redistribution, and epithelial leakage 3. RAC1 mediates exercise-induced muscle protein synthesis and glycogen resynthesis through p38MAPK signaling and NOX2-dependent mechanisms 4. RAC1 promotes smooth muscle contraction and proliferation via actin polymerization 5. Disease relevance is substantial: RAC1(P29S) is the third most common melanoma mutation (4-7% of patients), remaining constitutively GTP-bound and promoting proliferation and migration 6. RAC1 hyperactivation drives prostate cancer progression through VAV2-mediated EGFR signaling, with VAV2 overexpression correlating with poor prognosis 7. RAC1 silencing inhibits epithelial-mesenchymal transition and metastatic potential in gastric cancer 8. Mutations cause intellectual developmental disorder, autosomal dominant 48. RAC1 represents a therapeutic target across multiple cancers and inflammatory conditions.

Sources cited
1
RAC1 isoform B exhibits GTP-binding activity and GTPase-dependent regulation via GEFs and GAPs
PMID: 14625275
2
RAC1 mediates actin cytoskeleton reorganization and cell migration in lung adenocarcinoma through GEF-dependent activation
PMID: 34731623
3
Epithelial RAC1 controls cytoskeleton dynamics, cell mechanics, and cell shedding; impaired RAC1 function causes epithelial leakage and intestinal inflammation
PMID: 35241625
4
Skeletal muscle RAC1 mediates exercise training adaptations through p38MAPK signaling and NOX2-dependent glycogen resynthesis
PMID: 40886619
5
RAC1 promotes smooth muscle contraction and proliferation through actin polymerization
PMID: 40332567
6
RAC1(P29S) is the third most common melanoma mutation (4-7% of patients), remaining constitutively active and promoting cell proliferation and migration
PMID: 25465943
7
VAV2 mediates EGFR-induced Rac1 activation in prostate cancer, driving proliferation and migration with prognostic significance
PMID: 40183768
8
RAC1 silencing inhibits TGF-Ξ²1-induced epithelial-mesenchymal transition and promotes apoptosis in gastric cancer cells
PMID: 37434402
Disease Associationsβ“˜21
intellectual disability, autosomal dominant 48Open Targets
0.76Strong
melanomaOpen Targets
0.54Moderate
Abnormality of the skeletal systemOpen Targets
0.49Moderate
cutaneous melanomaOpen Targets
0.48Moderate
cutaneous LeishmaniasisOpen Targets
0.46Moderate
head and neck squamous cell carcinomaOpen Targets
0.45Moderate
genetic disorderOpen Targets
0.40Moderate
cancerOpen Targets
0.40Weak
neurodegenerative diseaseOpen Targets
0.38Weak
Neurodevelopmental disorderOpen Targets
0.37Weak
Intellectual disabilityOpen Targets
0.37Weak
HIV infectionOpen Targets
0.37Weak
nodular melanomaOpen Targets
0.37Weak
bile duct carcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
developmental disabilityOpen Targets
0.37Weak
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.37Weak
gliomatosis cerebriOpen Targets
0.37Weak
superficial spreading melanomaOpen Targets
0.37Weak
syndromic intellectual disabilityOpen Targets
0.37Weak
Intellectual developmental disorder, autosomal dominant 48UniProt
Pathogenic Variants25
NM_006908.5(RAC1):c.190T>G (p.Tyr64Asp)Pathogenic
Intellectual disability, autosomal dominant 48|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 64
NM_006908.5(RAC1):c.116A>G (p.Asn39Ser)Pathogenic
Intellectual disability, autosomal dominant 48|Global developmental delay|Neurodevelopmental delay|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 39
NM_006908.5(RAC1):c.151G>A (p.Val51Met)Pathogenic
Intellectual disability, autosomal dominant 48|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 51
NM_006908.5(RAC1):c.212C>T (p.Ser71Phe)Pathogenic
Intellectual disability, autosomal dominant 48|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 71
NM_006908.5(RAC1):c.218C>T (p.Pro73Leu)Pathogenic
See cases|not provided|Intellectual disability, autosomal dominant 48
β˜…β˜…β˜†β˜†2022β†’ Residue 73
NM_006908.5(RAC1):c.171T>G (p.Asp57Glu)Likely pathogenic
Intellectual disability, autosomal dominant 48
β˜…β˜†β˜†β˜†2025β†’ Residue 57
NM_006908.5(RAC1):c.178G>A (p.Gly60Arg)Likely pathogenic
Intellectual disability, autosomal dominant 48
β˜…β˜†β˜†β˜†2025β†’ Residue 60
NM_006908.5(RAC1):c.348A>C (p.Lys116Asn)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 116
NM_006908.5(RAC1):c.103A>G (p.Thr35Ala)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 35
NM_006908.5(RAC1):c.94T>C (p.Tyr32His)Pathogenic
Intellectual disability, autosomal dominant 48
β˜…β˜†β˜†β˜†2024β†’ Residue 32
NM_006908.5(RAC1):c.129T>A (p.Asn43Lys)Likely pathogenic
Intellectual disability, autosomal dominant 48
β˜…β˜†β˜†β˜†2024β†’ Residue 43
NM_006908.5(RAC1):c.53G>A (p.Cys18Tyr)Pathogenic
Intellectual disability, autosomal dominant 48|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 18
NM_006908.5(RAC1):c.181C>G (p.Gln61Glu)Pathogenic
Intellectual disability, autosomal dominant 48|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 61
NM_006908.5(RAC1):c.394A>G (p.Lys132Glu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 132
NM_006908.5(RAC1):c.151G>C (p.Val51Leu)Likely pathogenic
Intellectual disability, autosomal dominant 48|Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
β˜…β˜†β˜†β˜†2023β†’ Residue 51
NM_006908.5(RAC1):c.168G>C (p.Trp56Cys)Likely pathogenic
Intellectual disability, autosomal dominant 48
β˜…β˜†β˜†β˜†2023β†’ Residue 56
NM_006908.5(RAC1):c.190T>C (p.Tyr64His)Likely pathogenic
Intellectual disability, autosomal dominant 48
β˜…β˜†β˜†β˜†2022β†’ Residue 64
NM_006908.5(RAC1):c.184G>A (p.Glu62Lys)Pathogenic
Intellectual disability, autosomal dominant 48
β˜…β˜†β˜†β˜†2022β†’ Residue 62
NM_006908.5(RAC1):c.475G>A (p.Ala159Thr)Pathogenic
Intellectual disability, autosomal dominant 48
β˜…β˜†β˜†β˜†2022β†’ Residue 159
NM_006908.5(RAC1):c.191A>G (p.Tyr64Cys)Likely pathogenic
Intellectual disability, autosomal dominant 48
β˜…β˜†β˜†β˜†2022β†’ Residue 64
View on ClinVar β†—
Related Genes
NCF1Protein interaction100%CYFIP1Protein interaction100%ARHGEF7Protein interaction100%PREX1Protein interaction99%ARFIP2Protein interaction99%ELMO1Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Lung
47%
Heart
46%
Bone Marrow
33%
Ovary
33%
Liver
32%
Gene Interaction Network
Click a node to explore
RAC1NCF1CYFIP1ARHGEF7PREX1ARFIP2ELMO1
PROTEIN STRUCTURE
Preparing viewer…
PDB1MH1 Β· 1.38 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.25Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.05 [0.02–0.25]
RankingsWhere RAC1 stands among ~20K protein-coding genes
  • #101of 20,598
    Most Researched1,340 Β· top 1%
  • #1,959of 5,498
    Most Pathogenic Variants25
  • #769of 17,882
    Most Constrained (LOEUF)0.25 Β· top 5%
Genes detectedRAC1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
Epithelial RAC1-dependent cytoskeleton dynamics controls cell mechanics, cell shedding and barrier integrity in intestinal inflammation.
PMID: 35241625
Gut Β· 2023
1.00
2
FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma.
PMID: 34731623
Cell Rep Β· 2021
0.90
3
Small GTPase Rac1: structure, localization, and expression of the human gene.
PMID: 11062023
Biochem Biophys Res Commun Β· 2000
0.86
4
Glioblastoma- derived exosomes (GBM-Exo) regulate microglial M2 polarization via the RAC1/AKT/NRF2 pathway.
PMID: 40019712
J Neurooncol Β· 2025
0.82
5
RAC1 Takes the Lead in Solid Tumors.
PMID: 31027363
Cells Β· 2019
0.80