Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It may form a complex with G proteins and stimulate Rho-dependent signals. ... See more...

Aliases for ARHGEF6 Gene

Aliases for ARHGEF6 Gene

  • Rac/Cdc42 Guanine Nucleotide Exchange Factor 6 2 3 4 5
  • Rho Guanine Nucleotide Exchange Factor 6 2 3 4
  • Rac/Cdc42 Guanine Nucleotide Exchange Factor (GEF) 6 2 3
  • Rac/Cdc42 Guanine Exchange Factor (GEF) 6 2 3
  • PAK-Interacting Exchange Factor, Alpha 2 3
  • Alpha-PIX 2 3
  • AlphaPIX 2 3
  • KIAA0006 2 4
  • Cool-2 2 3
  • COOL2 3 4
  • PIXA 3 4
  • PAK-Interacting Exchange Factor Alpha 4
  • Mental Retardation, X-Linked 46 2
  • Alpha-Pix 4
  • ARHGEF6 5
  • COOL-2 4
  • MRX46 3
  • Cool2 2
  • ΑPix 2

External Ids for ARHGEF6 Gene

Previous HGNC Symbols for ARHGEF6 Gene

  • MRX46

Previous GeneCards Identifiers for ARHGEF6 Gene

  • GC0XM130319
  • GC0XM132593
  • GC0XM133692
  • GC0XM134453
  • GC0XM135473
  • GC0XM135575
  • GC0XM135747
  • GC0XM125018

Summaries for ARHGEF6 Gene

Entrez Gene Summary for ARHGEF6 Gene

  • Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It may form a complex with G proteins and stimulate Rho-dependent signals. This protein is activated by PI3-kinase. Mutations in this gene can cause X-chromosomal non-specific cognitive disability. [provided by RefSeq, Jul 2008]

GeneCards Summary for ARHGEF6 Gene

ARHGEF6 (Rac/Cdc42 Guanine Nucleotide Exchange Factor 6) is a Protein Coding gene. Diseases associated with ARHGEF6 include Non-Syndromic X-Linked Intellectual Disability and Syndromic X-Linked Intellectual Disability. Among its related pathways are Guidance Cues and Growth Cone Motility and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include GTPase activator activity and Rho guanyl-nucleotide exchange factor activity. An important paralog of this gene is ARHGEF7.

UniProtKB/Swiss-Prot Summary for ARHGEF6 Gene

Gene Wiki entry for ARHGEF6 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ARHGEF6 Gene

Genomics for ARHGEF6 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ARHGEF6 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ136778 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE dbSUPER 610.6 -0.6 -556 6.8 ZHX2 FOXA1 PKNOX1 POLR2A EP300 SP1 HMBOX1 CTBP1 RUNX3 HDAC2 ARHGEF6 ENSG00000234062 LOC100422685 RBMX
GH0XJ136878 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 12.5 -98.9 -98855 4 SP1 CREB1 PRDM10 ZNF629 REST ZNF692 POLR2A FOS DDX20 PRDM1 RBMX SNORD61 lnc-ARHGEF6-4 piR-57133-655 ENSG00000234062 SRRM1P3 ARHGEF6 ENSG00000232611
GH0XJ136764 Promoter/Enhancer 1.8 Ensembl ENCODE CraniofacialAtlas dbSUPER 13.4 +13.7 13740 4.8 HNRNPL PRDM10 ZNF629 ZNF512 LEF1 IKZF1 ZNF692 JUND MTA2 PRDM1 5MWI_A-198 ARHGEF6 ENSG00000234062 piR-38579-044 CD40LG
GH0XJ136744 Enhancer 0.9 ENCODE dbSUPER 11.4 +34.3 34312 3.6 JUND MTA1 HDAC1 ETV6 SOX6 EP300 HMBOX1 CTBP1 HES1 HDAC2 ARHGEF6 lnc-CD40LG-3 piR-38579-044 CD40LG
GH0XJ136884 Enhancer 1.1 Ensembl ENCODE 8.5 -104.7 -104657 3.2 PRDM10 ZNF629 LEF1 IKZF1 ZNF692 ETV6 JUND MTA2 PKNOX1 MTA1 RF00017-8757 ARHGEF6 RBMX RF00017-8758 GPR101
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ARHGEF6 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ARHGEF6

Top Transcription factor binding sites by QIAGEN in the ARHGEF6 gene promoter:
  • C/EBPalpha
  • CHOP-10
  • FOXI1
  • HFH-3
  • HOXA9
  • HOXA9B
  • Meis-1b
  • MRF-2
  • Nkx2-5
  • POU3F2

Genomic Locations for ARHGEF6 Gene

Genomic Locations for ARHGEF6 Gene
chrX:136,665,547-136,780,945
(GRCh38/hg38)
Size:
115,399 bases
Orientation:
Minus strand
chrX:135,747,706-135,864,247
(GRCh37/hg19)
Size:
116,542 bases
Orientation:
Minus strand

Genomic View for ARHGEF6 Gene

Genes around ARHGEF6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ARHGEF6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ARHGEF6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ARHGEF6 Gene

Proteins for ARHGEF6 Gene

  • Protein details for ARHGEF6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q15052-ARHG6_HUMAN
    Recommended name:
    Rho guanine nucleotide exchange factor 6
    Protein Accession:
    Q15052
    Secondary Accessions:
    • A6NMW9
    • A8K6S7
    • B1AL37
    • Q15396
    • Q5JQ66
    • Q7Z3W1
    • Q86XH0

    Protein attributes for ARHGEF6 Gene

    Size:
    776 amino acids
    Molecular mass:
    87499 Da
    Quaternary structure:
    • Interacts with PAK kinases through the SH3 domain. Interacts with GIT1. Component of cytoplasmic complexes, which also contain PXN, GIT1 and PAK1 (By similarity). Interacts with PARVB. Interacts with BIN2. Identified in a complex with BIN2 and GIT2.
    SequenceCaution:
    • Sequence=BAA02796.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ARHGEF6 Gene

    Alternative splice isoforms for ARHGEF6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ARHGEF6 Gene

Post-translational modifications for ARHGEF6 Gene

  • Ubiquitination at Lys682, Lys712, Lys722, and Lys736
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for ARHGEF6 Gene

Domains & Families for ARHGEF6 Gene

Gene Families for ARHGEF6 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for ARHGEF6 Gene

InterPro:
Blocks:
  • SH3 domain signature
  • Pleckstrin-like
  • DH domain
  • Calponin-like actin-binding
ProtoNet:

Suggested Antigen Peptide Sequences for ARHGEF6 Gene

GenScript: Design optimal peptide antigens:
  • Rac/Cdc42 guanine nucleotide exchange factor 6 (ARHG6_HUMAN)
  • cDNA FLJ51737, highly similar to Rho guanine nucleotide exchange factor 6 (B1AL37_HUMAN)
  • cDNA FLJ50776, highly similar to Rho guanine nucleotide exchange factor 6 (B7Z3C7_HUMAN)
genes like me logo Genes that share domains with ARHGEF6: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for ARHGEF6 Gene

Function for ARHGEF6 Gene

Molecular function for ARHGEF6 Gene

UniProtKB/Swiss-Prot Function:
Acts as a RAC1 guanine nucleotide exchange factor (GEF).

Phenotypes From GWAS Catalog for ARHGEF6 Gene

Gene Ontology (GO) - Molecular Function for ARHGEF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity TAS --
GO:0005089 Rho guanyl-nucleotide exchange factor activity NAS 11017088
GO:0005096 GTPase activator activity NAS 9582122
GO:0005515 protein binding IPI 11864573
genes like me logo Genes that share ontologies with ARHGEF6: view
genes like me logo Genes that share phenotypes with ARHGEF6: view

Human Phenotype Ontology for ARHGEF6 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ARHGEF6 Gene

MGI Knock Outs for ARHGEF6:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ARHGEF6

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for ARHGEF6 Gene

Localization for ARHGEF6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ARHGEF6 Gene

Cell projection, lamellipodium.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ARHGEF6 gene
Compartment Confidence
cytosol 5
plasma membrane 2
cytoskeleton 2
nucleus 2
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for ARHGEF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0030027 lamellipodium ISS --
GO:0042995 cell projection IEA --
genes like me logo Genes that share ontologies with ARHGEF6: view

Pathways & Interactions for ARHGEF6 Gene

PathCards logo

SuperPathways for ARHGEF6 Gene

SuperPathway Contained pathways
1 GPCR Pathway
.73
.73
.62
.59
.58
2 p75 NTR receptor-mediated signalling
3 Cell junction organization
4 G-AlphaQ Signaling
.47
.47
.40
5 ERK Signaling
.61
.51
.49
genes like me logo Genes that share pathways with ARHGEF6: view

Pathways by source for ARHGEF6 Gene

2 KEGG pathways for ARHGEF6 Gene
28 Qiagen pathways for ARHGEF6 Gene
  • Activation of PKC through GPCR
  • Agrin Interactions at Neuromuscular Junction
  • Breast Cancer Regulation by Stathmin1
  • CDC42 Pathway
  • CXCR4 Pathway
2 Cell Signaling Technology pathways for ARHGEF6 Gene

Gene Ontology (GO) - Biological Process for ARHGEF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process NAS 11564864
GO:0007186 G protein-coupled receptor signaling pathway TAS --
GO:0007254 JNK cascade NAS 11564864
GO:0030032 lamellipodium assembly ISS --
GO:0043065 positive regulation of apoptotic process TAS --
genes like me logo Genes that share ontologies with ARHGEF6: view

No data available for SIGNOR curated interactions for ARHGEF6 Gene

Drugs & Compounds for ARHGEF6 Gene

(3) Drugs for ARHGEF6 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Guanosine diphosphate Experimental Pharma 0
Guanosine monophosphate Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0
genes like me logo Genes that share compounds with ARHGEF6: view

Transcripts for ARHGEF6 Gene

mRNA/cDNA for ARHGEF6 Gene

2 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ARHGEF6

Alternative Splicing Database (ASD) splice patterns (SP) for ARHGEF6 Gene

No ASD Table

Relevant External Links for ARHGEF6 Gene

GeneLoc Exon Structure for
ARHGEF6

Expression for ARHGEF6 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ARHGEF6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for ARHGEF6 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (18.6) and Lymph node (17.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ARHGEF6 Gene



Protein tissue co-expression partners for ARHGEF6 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ARHGEF6

SOURCE GeneReport for Unigene cluster for ARHGEF6 Gene:

Hs.522795

mRNA Expression by UniProt/SwissProt for ARHGEF6 Gene:

Q15052-ARHG6_HUMAN
Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for ARHGEF6 Gene

  • Nervous system(4.8)
  • Bone marrow(4.3)
  • Liver(4.3)
  • Blood(2.3)
  • Muscle(2.2)
  • Heart(2.2)
  • Spleen(2.2)
  • Lymph node(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ARHGEF6 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • cheek
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • nose
  • outer ear
  • salivary gland
  • skull
  • tooth
Thorax:
  • lung
  • rib
  • rib cage
Pelvis:
  • pelvis
  • testicle
  • urinary bladder
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with ARHGEF6: view

No data available for mRNA differential expression in normal tissues for ARHGEF6 Gene

Orthologs for ARHGEF6 Gene

This gene was present in the common ancestor of animals.

Orthologs for ARHGEF6 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ARHGEF6 30 31
  • 96.5 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ARHGEF6 30 31
  • 92.44 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ARHGEF6 30 31
  • 91.61 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Arhgef6 30
  • 89.06 (n)
Mouse
(Mus musculus)
Mammalia Arhgef6 30 17 31
  • 88.83 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia ARHGEF6 31
  • 81 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia ARHGEF6 31
  • 80 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ARHGEF6 30 31
  • 72.21 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ARHGEF6 31
  • 70 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia arhgef6 30
  • 70.27 (n)
Zebrafish
(Danio rerio)
Actinopterygii LOC558288 30
  • 63.32 (n)
arhgef6 31
  • 61 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta rtGEF 31 32
  • 15 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea pix-1 31
  • 26 (a)
OneToMany
K11E4.4 32
  • 26 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.2909 31
  • 39 (a)
OneToMany
Species where no ortholog for ARHGEF6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for ARHGEF6 Gene

ENSEMBL:
Gene Tree for ARHGEF6 (if available)
TreeFam:
Gene Tree for ARHGEF6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ARHGEF6: view image

Paralogs for ARHGEF6 Gene

(6) SIMAP similar genes for ARHGEF6 Gene using alignment to 2 proteins:

  • ARHG6_HUMAN
  • B7Z3C7_HUMAN
genes like me logo Genes that share paralogs with ARHGEF6: view

Variants for ARHGEF6 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ARHGEF6 Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
697653 Likely Benign: not provided 136,681,946(-) G/A MISSENSE_VARIANT
702565 Benign: not provided 136,708,742(-) G/A SYNONYMOUS_VARIANT
722167 Likely Benign: not provided 136,732,177(-) G/GA INTRON_VARIANT
769329 Likely Benign: not provided 136,668,145(-) G/T MISSENSE_VARIANT
771624 Benign: not provided 136,679,646(-) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for ARHGEF6 Gene

Structural Variations from Database of Genomic Variants (DGV) for ARHGEF6 Gene

Variant ID Type Subtype PubMed ID
nsv7109 CNV insertion 18451855

Variation tolerance for ARHGEF6 Gene

Residual Variation Intolerance Score: 21% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.12; 38.69% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ARHGEF6 Gene

Human Gene Mutation Database (HGMD)
ARHGEF6
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ARHGEF6

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ARHGEF6 Gene

Disorders for ARHGEF6 Gene

MalaCards: The human disease database

(3) MalaCards diseases for ARHGEF6 Gene - From: Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
non-syndromic x-linked intellectual disability
  • non-specific x-linked mental retardation
syndromic x-linked intellectual disability
  • x-linked syndromic intellectual disability
deafness, autosomal recessive 104
  • dfnb104
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for ARHGEF6

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with ARHGEF6: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ARHGEF6 Gene

Publications for ARHGEF6 Gene

  1. Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for Rho GTPases, in patients with X-linked mental retardation. (PMID: 11017088) Kutsche K … Gal A (Nature genetics 2000) 3 4 23
  2. Mutation of ARHGAP9 in patients with coronary spastic angina. (PMID: 19911011) Takefuji M … Kaibuchi K (Journal of human genetics 2010) 3 41
  3. PAK4 and alphaPIX determine podosome size and number in macrophages through localized actin regulation. (PMID: 16897755) Gringel A … Linder S (Journal of cellular physiology 2006) 3 23
  4. Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, alpha-PIX and sorcin. (PMID: 16320026) Yokota T … Tsunoda T (Acta neuropathologica 2006) 3 23
  5. The DNA sequence of the human X chromosome. (PMID: 15772651) Ross MT … Bentley DR (Nature 2005) 3 4

Products for ARHGEF6 Gene

Sources for ARHGEF6 Gene