Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. This gene encodes a protein that functions as a specific guanine nucleotide exchange factor for RhoA. It also interacts with ephrin A4 in vascular smooth muscle cells. Two alternatively spliced transcripts variants that en... See more...

Aliases for ARHGEF15 Gene

Aliases for ARHGEF15 Gene

  • Rho Guanine Nucleotide Exchange Factor 15 2 3 3 4 5
  • Vsm-RhoGEF 2 3 4
  • Rho Guanine Nucleotide Exchange Factor (GEF) 15 2 3
  • Ephexin-5 3 4
  • Ephexin5 2 3
  • KIAA0915 2 4
  • ARGEF15 2 3
  • E5 3 4
  • Rho Guanine Exchange Factor (GEF) 15 2
  • ARHGEF15 5
  • FLJ13791 2
  • MGC44868 2

External Ids for ARHGEF15 Gene

Previous GeneCards Identifiers for ARHGEF15 Gene

  • GC17P008591
  • GC17P009307
  • GC17P008156
  • GC17P008414
  • GC17P008154
  • GC17P008108
  • GC17P008213

Summaries for ARHGEF15 Gene

Entrez Gene Summary for ARHGEF15 Gene

  • Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. This gene encodes a protein that functions as a specific guanine nucleotide exchange factor for RhoA. It also interacts with ephrin A4 in vascular smooth muscle cells. Two alternatively spliced transcripts variants that encode the same protein have been found for this gene. [provided by RefSeq, Aug 2010]

GeneCards Summary for ARHGEF15 Gene

ARHGEF15 (Rho Guanine Nucleotide Exchange Factor 15) is a Protein Coding gene. Diseases associated with ARHGEF15 include Spastic Ataxia, Charlevoix-Saguenay Type and Early Infantile Epileptic Encephalopathy. 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 ARHGEF5.

UniProtKB/Swiss-Prot Summary for ARHGEF15 Gene

  • Specific GEF for RhoA activation. Does not activate RAC1 or CDC42. Regulates vascular smooth muscle contractility. Negatively regulates excitatory synapse development by suppressing the synapse-promoting activity of EPHB2.

Additional gene information for ARHGEF15 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ARHGEF15 Gene

Genomics for ARHGEF15 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ARHGEF15 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
GH17J008310 Promoter/Enhancer 1.3 EPDnew Ensembl ENCODE 600.7 +1.1 1059 2.6 ZSCAN4 HDAC1 SOX6 NR2F2 ZFHX2 VEZF1 NRF1 GLIS1 ZNF398 KDM1A ARHGEF15 CTC1 SLC25A35 PFAS ENSG00000212206 ENSG00000226871 ODF4
GH17J008309 Enhancer 0.2 Ensembl 600.7 -0.5 -540 0.2 ARHGEF15 RF00017-2271 SLC25A35
GH17J008292 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 5.5 -15.9 -15940 4.6 SP1 GATAD2A PRDM10 REST LEF1 IKZF1 KDM1A POLR2A RCOR2 FOS SLC25A35 lnc-ARHGEF15-1 ATP1B2 VAMP2 NLGN2 CTC1 PFAS ARHGEF15 ENSG00000271029 lnc-SLC25A35-2
GH17J008209 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 4.9 -100.1 -100140 3.4 SP1 CREB1 GATAD2A ATF7 ZNF629 PRDM10 IKZF1 NFKBIZ KDM1A ZNF692 AURKB lnc-AURKB-3 lnc-BORCS6-1 PFAS DVL2 NLGN2 CTC1 ENSG00000265749 CYB5D1 CNTROB
GH17J008288 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 4.7 -21.4 -21403 2.9 SP1 HNRNPL PRDM10 ZNF629 NFKBIZ ZNF692 POLR2A LARP7 ZNF143 ZIC2 RANGRF lnc-CTC1-4 PFAS ARHGEF15 SLC25A35
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ARHGEF15 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ARHGEF15

Top Transcription factor binding sites by QIAGEN in the ARHGEF15 gene promoter:
  • c-Jun
  • C/EBPbeta
  • Chx10
  • NF-kappaB
  • NF-kappaB1
  • Pax-4a
  • RP58
  • SREBP-1a
  • SREBP-1b
  • SREBP-1c

Genomic Locations for ARHGEF15 Gene

Genomic Locations for ARHGEF15 Gene
chr17:8,310,241-8,322,516
(GRCh38/hg38)
Size:
12,276 bases
Orientation:
Plus strand
chr17:8,213,556-8,225,834
(GRCh37/hg19)
Size:
12,279 bases
Orientation:
Plus strand

Genomic View for ARHGEF15 Gene

Genes around ARHGEF15 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ARHGEF15 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ARHGEF15 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ARHGEF15 Gene

Proteins for ARHGEF15 Gene

  • Protein details for ARHGEF15 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O94989-ARHGF_HUMAN
    Recommended name:
    Rho guanine nucleotide exchange factor 15
    Protein Accession:
    O94989
    Secondary Accessions:
    • A8K6G1
    • Q8N449
    • Q9H8B4

    Protein attributes for ARHGEF15 Gene

    Size:
    841 amino acids
    Molecular mass:
    91940 Da
    Quaternary structure:
    • Interacts with EPHB2 (By similarity). Interacts with EPHA4.
    SequenceCaution:
    • Sequence=BAA74938.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

neXtProt entry for ARHGEF15 Gene

Post-translational modifications for ARHGEF15 Gene

  • Phosphorylated on tyrosine residues upon EFNA1 stimulation. EPHB2-dependent phosphorylation at Tyr-353 triggers UBE3A-mediated ubiquitination (By similarity).
  • Ubiquitinated; UBE3A-mediated ubiquitination and degradation by the proteasome promotes EFNB1-dependent synapse formation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for ARHGEF15 Gene

Domains & Families for ARHGEF15 Gene

Gene Families for ARHGEF15 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for ARHGEF15 Gene

InterPro:
Blocks:
  • DH domain
ProtoNet:

Suggested Antigen Peptide Sequences for ARHGEF15 Gene

GenScript: Design optimal peptide antigens:
  • Vsm-RhoGEF (ARHGF_HUMAN)
  • Rho guanine nucleotide exchange factor (GEF) 15, isoform CRA_a (D3DTR7_HUMAN)
  • E5 protein (Q8WXV7_HUMAN)
genes like me logo Genes that share domains with ARHGEF15: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for ARHGEF15 Gene

Function for ARHGEF15 Gene

Molecular function for ARHGEF15 Gene

UniProtKB/Swiss-Prot Function:
Specific GEF for RhoA activation. Does not activate RAC1 or CDC42. Regulates vascular smooth muscle contractility. Negatively regulates excitatory synapse development by suppressing the synapse-promoting activity of EPHB2.

Phenotypes From GWAS Catalog for ARHGEF15 Gene

Gene Ontology (GO) - Molecular Function for ARHGEF15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity IEA --
GO:0005089 Rho guanyl-nucleotide exchange factor activity ISS --
GO:0005096 GTPase activator activity IEA --
GO:0005515 protein binding IPI 12775584
genes like me logo Genes that share ontologies with ARHGEF15: view
genes like me logo Genes that share phenotypes with ARHGEF15: view

Animal Models for ARHGEF15 Gene

MGI Knock Outs for ARHGEF15:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ARHGEF15

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ARHGEF15 Gene

Localization for ARHGEF15 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ARHGEF15 Gene

Cell projection, dendrite. Note=Expressed exclusively in dendrites of the developing hippocampus. {ECO:0000250}.

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 ARHGEF15 gene
Compartment Confidence
nucleus 2
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ARHGEF15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm ISS --
GO:0030425 dendrite ISS --
GO:0042995 cell projection IEA --
genes like me logo Genes that share ontologies with ARHGEF15: view

Pathways & Interactions for ARHGEF15 Gene

PathCards logo

SuperPathways for ARHGEF15 Gene

SuperPathway Contained pathways
1 p75 NTR receptor-mediated signalling
2 GPCR Pathway
.73
.62
.59
.58
3 Signaling by GPCR
4 fMLP Pathway
.39
.31
5 G-AlphaQ Signaling
.47
.47
genes like me logo Genes that share pathways with ARHGEF15: view

Pathways by source for ARHGEF15 Gene

19 Qiagen pathways for ARHGEF15 Gene
  • Breast Cancer Regulation by Stathmin1
  • CXCR4 Pathway
  • G-AlphaI Signaling
  • G-AlphaQ Signaling
  • GPCR Pathway

SIGNOR curated interactions for ARHGEF15 Gene

Activates:

Gene Ontology (GO) - Biological Process for ARHGEF15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0043547 positive regulation of GTPase activity IEA --
GO:0050790 regulation of catalytic activity IDA 12775584
GO:0051496 positive regulation of stress fiber assembly ISS --
GO:0061299 retina vasculature morphogenesis in camera-type eye IEA --
GO:0090630 activation of GTPase activity IBA 21873635
genes like me logo Genes that share ontologies with ARHGEF15: view

Drugs & Compounds for ARHGEF15 Gene

No Compound Related Data Available

Transcripts for ARHGEF15 Gene

mRNA/cDNA for ARHGEF15 Gene

2 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
9 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 ARHGEF15

Alternative Splicing Database (ASD) splice patterns (SP) for ARHGEF15 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4a · 4b ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18
SP1: - - - -
SP2:
SP3: -
SP4:

Relevant External Links for ARHGEF15 Gene

GeneLoc Exon Structure for
ARHGEF15

Expression for ARHGEF15 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ARHGEF15 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ARHGEF15 Gene

This gene is overexpressed in Adipose - Visceral (Omentum) (x5.5) and Adipose - Subcutaneous (x4.8).

Protein differential expression in normal tissues from HIPED for ARHGEF15 Gene

This gene is overexpressed in Placenta (35.5) and Synovial fluid (28.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ARHGEF15 Gene



Protein tissue co-expression partners for ARHGEF15 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ARHGEF15

SOURCE GeneReport for Unigene cluster for ARHGEF15 Gene:

Hs.443109

mRNA Expression by UniProt/SwissProt for ARHGEF15 Gene:

O94989-ARHGF_HUMAN
Tissue specificity: Expressed in the vascular smooth muscle of coronary artery.

Evidence on tissue expression from TISSUES for ARHGEF15 Gene

  • Nervous system(4.4)
  • Lung(4.3)
  • Skin(2.1)
genes like me logo Genes that share expression patterns with ARHGEF15: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ARHGEF15 Gene

Orthologs for ARHGEF15 Gene

This gene was present in the common ancestor of animals.

Orthologs for ARHGEF15 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ARHGEF15 30 31
  • 99.33 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ARHGEF15 30 31
  • 87.28 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ARHGEF15 30 31
  • 86.26 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Arhgef15 30 17 31
  • 84.33 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Arhgef15 30
  • 83 (n)
Oppossum
(Monodelphis domestica)
Mammalia ARHGEF15 31
  • 63 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 37 (a)
ManyToMany
Lizard
(Anolis carolinensis)
Reptilia ARHGEF15 31
  • 38 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii arhgef15 31
  • 42 (a)
OneToMany
ARHGEF15 (2 of 2) 31
  • 29 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta Exn 31
  • 12 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea ephx-1 31
  • 16 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 29 (a)
OneToMany
Species where no ortholog for ARHGEF15 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)
  • Chicken (Gallus gallus)
  • 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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for ARHGEF15 Gene

ENSEMBL:
Gene Tree for ARHGEF15 (if available)
TreeFam:
Gene Tree for ARHGEF15 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ARHGEF15: view image

Paralogs for ARHGEF15 Gene

Paralogs for ARHGEF15 Gene

(4) SIMAP similar genes for ARHGEF15 Gene using alignment to 5 proteins:

  • ARHGF_HUMAN
  • D3DTR7_HUMAN
  • J3KT46_HUMAN
  • J3QQS4_HUMAN
  • J3QS60_HUMAN
genes like me logo Genes that share paralogs with ARHGEF15: view

Variants for ARHGEF15 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ARHGEF15 Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
639089 Uncertain Significance: Early infantile epileptic encephalopathy 8,312,538(+) G/T MISSENSE_VARIANT
639110 Uncertain Significance: Early infantile epileptic encephalopathy 8,320,952(+) G/A MISSENSE_VARIANT
639737 Uncertain Significance: Early infantile epileptic encephalopathy 8,312,107(+) G/A MISSENSE_VARIANT
643626 Uncertain Significance: Early infantile epileptic encephalopathy 8,312,383(+) G/A MISSENSE_VARIANT
644747 Uncertain Significance: Early infantile epileptic encephalopathy 8,315,892(+) C/G MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for ARHGEF15 Gene

Structural Variations from Database of Genomic Variants (DGV) for ARHGEF15 Gene

Variant ID Type Subtype PubMed ID
esv3639881 CNV gain 21293372
esv3639882 CNV gain 21293372
nsv1967 CNV deletion 18451855
nsv457664 CNV gain 19166990
nsv470576 CNV gain 18288195
nsv527633 CNV loss 19592680
nsv574337 CNV gain 21841781
nsv833353 CNV loss 17160897

Variation tolerance for ARHGEF15 Gene

Residual Variation Intolerance Score: 70.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.72; 66.24% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ARHGEF15 Gene

Human Gene Mutation Database (HGMD)
ARHGEF15
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ARHGEF15

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ARHGEF15 Gene

Disorders for ARHGEF15 Gene

MalaCards: The human disease database

(3) MalaCards diseases for ARHGEF15 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
spastic ataxia, charlevoix-saguenay type
  • sacs
early infantile epileptic encephalopathy
  • early infantile epileptic encephalopathy with burst-suppression
angelman syndrome
  • as
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for ARHGEF15

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 ARHGEF15: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ARHGEF15 Gene

Publications for ARHGEF15 Gene

  1. EphA4-mediated Rho activation via Vsm-RhoGEF expressed specifically in vascular smooth muscle cells. (PMID: 12775584) Ogita H … Mochizuki N (Circulation research 2003) 3 4 23
  2. Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PMID: 10048485) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1998) 2 3 4
  3. Mutation of ARHGAP9 in patients with coronary spastic angina. (PMID: 19911011) Takefuji M … Kaibuchi K (Journal of human genetics 2010) 3 41
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4

Products for ARHGEF15 Gene

Sources for ARHGEF15 Gene