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Symbol ARHGEF6 contributors: mct - updated : 10-01-2017
HGNC name Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6
HGNC id 685
Corresponding disease
MRX46 mental retardation, 46
Location Xq26.3      Physical location : 135.747.713 - 135.863.503
Synonym name
  • PAK-interacting exchange factor alpha
  • rho guanine nucleotide exchange factor 6
  • Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6
  • Rac/Cdc42 guanine exchange factor (GEF) 6
  • Synonym symbol(s) COOL2, COOL-2, ALPHAPIX, KIAA0006, ALPHA-PIX, PIXA
    TYPE functioning gene
    STRUCTURE 116.11 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC392545 X similar to high mobility group protein homolog HMG4 LOC389887 X similar to RIKEN cDNA 1110012O05 CXX1 Xq26 CAAX box 1 DKFZP564B147 Xq26.3 DKFZP564B147 protein LOC159049 Xq26.3 hypothetical LOC159049 FLJ20527 Xq26.3 hypothetical protein FLJ20527 LOC392546 X similar to hypothetical protein FLJ20527 LOC389888 X similar to hypothetical protein FLJ20527 LOC389889 X hypothetical gene supported by BC061642 ZNF75 Xq26 zinc finger protein 75 (D8C6) FLJ23614 Xq26.3 hypothetical protein FLJ23614 LOC392547 X similar to KIAA0445 protein LOC203522 Xq26.3 hypothetical protein LOC203522 LOC392548 X similar to C-ets-2 protein LOC139587 Xq26.3 similar to sarcoma antigen; putative tumor antigen MGC27005 Xq26.3 hypothetical protein MGC27005 SAGE Xq28 hypothetical protein MGC27005 LOC93380 Xq26.3 hypothetical protein LOC93380 SLC9A6 Xq26.3 solute carrier family 9 (sodium/hydrogen exchanger), isoform 6 LOC392549 X similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) LOC139542 Xq26.3 similar to E2F transcription factor 6 isoform a FHL1 Xq26 four and a half LIM domains 1 FLJ12649 Xq26.3 hypothetical protein FLJ12649 GPR112 Xq26.3 G protein-coupled receptor 112 BRS3 Xq26-q28 bombesin-like receptor 3 HTATSF1 Xq26-Xq27 HIV TAT specific factor 1 VGLL1 Xq26.3 vestigial like 1 (Drosophila) TNFSF5 Xq26 tumor necrosis factor (ligand) superfamily, member 5 (hyper-IgM syndrome) ARHGEF6 Xq26 Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 LOC392550 X similar to ribosomal protein L7 LOC392551 X similar to Ras-related protein Rab-28 (Rab-26) RBMX Xq26 RNA binding motif protein, X chromosome LOC389890 X hypothetical gene supported by AF419855; NM_005839 LOC389891 X similar to ENSANGP00000013187 GPR101 Xq25-27.1 G protein-coupled receptor 101 LOC286472 Xq26.3 similar to Ras-related C3 botulinum toxin substrate homolog DJ20J23.1 ZIC3 Xq26.2 Zic family member 3 heterotaxy 1 (odd-paired homolog, Drosophila) LOC389892 X similar to Mothers against decapentaplegic homolog interacting protein (Madh-interacting protein) (Smad anchor for receptor activation) (Receptor activation anchor) (hSARA) (Novel serine protease) (NSP)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 5282 - 776 - 2015 26507661
    21 - 4820 - 622 - 2015 26507661
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
     thymus   highly
    Cardiovascularheart   highly
    Nervousbrain     Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period pregnancy
    Text placenta
  • a N terminal calponin homology domain,(unique to ARHGEF6)
  • a SH3 homology domain
  • a Dbl and a pleckstrin homology (PH) domains
    interspecies homolog to rattus arhgef6
  • cytoplasmic proteins family
  • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,intermed filament
  • lamellipodia
  • is localized to dendritic spines
  • basic FUNCTION
  • activator of Ras-like family of Rho proteins by exchanging bound GDP for GTP
  • putatively involved in axonal outgrowth,control of shape and size of dendrites
  • invoved in integrin-mediated signaling leading to activation of the GTPases RAC1 and/or CDC42
  • ARHGEF6 is localized in dendritic spines where it contributes to regulate spine morphogenesis probably by acting through a downstream activation of PAK3
  • ARHGEF6 and GIT2 are required for neuronal differentiation
  • RELN and the CDC42/RAC1 guanine nucleotide exchange factor ARHGEF6 promote dendritic Golgi translocation in hippocampal neurons
  • is a regulator of thymocyte migration and subsequent arrest that is linked to positive selection
  • recycling regulator ARHGEF6 and the degradation factor CBL closely cooperate in the regulation of EGFR trafficking
  • ARHGEF6 and ARHGEF7, respectively, are guanine nucleotide exchange factors (activators) for the Rho family small GTP-binding protein family members RAC1 and CDC42
  • CELLULAR PROCESS cell life, proliferation/growth
    cell migration & motility
    signaling signal transduction
    a component
    small molecule
  • interacting with PARVB (involved in reorganization of subsarcolemmal cytoskeletal actin by activation of RAC1 through ARHGEF6 and ARHGEF7 in skeletal muscle) (Matsuda 2008)
  • CBL negatively regulates ARHGEF6-mediated cell migration and invasion and the lack of CBL in the C6 and A172 glioma cells is respon
  • phosphorylated state of ARHGEF6 was required to activate first RAC1 and subsequently PYGM
  • interacts with the E3 ubiquitin ligase CBL, an enzyme that attaches ubiquitin to EGFR, thereby labelling this tyrosine kinase receptor for lysosomal degradation
  • function of ARHGEF6 as a strong promoter of EGFR recycling
  • ARHGEF6 is constitutively linked to GIT1, a GAP of Arf family small G proteins, and ARHGEF6 phosphorylation enables binding of the 14-3-3 adaptor protein to the ARHGEF6/GIT1 complex
  • cell & other
    Phosphorylated by PRKCQ (to activate RAC1 and consequently PYGM, PRKCQ phosphorylates ARHGEF6 in T cells)
    corresponding disease(s) MRX46
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    deleted in gastric carcinoma
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • imbalance in activity of different Rho GTPases may underlie altered neuronal connectivity and impaired synaptic function and cognition in Arhgef6 knockout mice