The protein encoded by this gene is a Rho-like GTPase that switches between the active (GTP-bound) state and inactive (GDP-bound) state to regulate CDC42 and other genes. This brain-specific protein also acts as an adaptor protein for the recruitment of gephyrin and together these proteins facilitate receceptor recruitement in GABAnergic and glycinergic synapses. Defects in thi... See more...

Aliases for ARHGEF9 Gene

Aliases for ARHGEF9 Gene

  • Cdc42 Guanine Nucleotide Exchange Factor 9 2 3 5
  • Cdc42 Guanine Nucleotide Exchange Factor (GEF) 9 2 3
  • Rac/Cdc42 Guanine Nucleotide Exchange Factor 9 3 4
  • Rho Guanine Nucleotide Exchange Factor 9 3 4
  • PEM-2 Homolog 3 4
  • Collybistin 2 4
  • KIAA0424 2 4
  • PEM-2 2 3
  • HPEM-2 Collybistin 3
  • COLLYBISTIN 3
  • ARHGEF9 5
  • HPEM-2 3
  • ARHDH9 4
  • EIEE8 3
  • PEM2 3

External Ids for ARHGEF9 Gene

Previous GeneCards Identifiers for ARHGEF9 Gene

  • GC0XM059065
  • GC0XM060320
  • GC0XM061088
  • GC0XM061722
  • GC0XM061723
  • GC0XM062637
  • GC0XM062771
  • GC0XM056681

Summaries for ARHGEF9 Gene

Entrez Gene Summary for ARHGEF9 Gene

  • The protein encoded by this gene is a Rho-like GTPase that switches between the active (GTP-bound) state and inactive (GDP-bound) state to regulate CDC42 and other genes. This brain-specific protein also acts as an adaptor protein for the recruitment of gephyrin and together these proteins facilitate receceptor recruitement in GABAnergic and glycinergic synapses. Defects in this gene are the cause of startle disease with epilepsy (STHEE), also known as hyperekplexia with epilepsy, as well as several other types of cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

GeneCards Summary for ARHGEF9 Gene

ARHGEF9 (Cdc42 Guanine Nucleotide Exchange Factor 9) is a Protein Coding gene. Diseases associated with ARHGEF9 include Epileptic Encephalopathy, Early Infantile, 8 and Hyperekplexia. Among its related pathways are Guidance Cues and Growth Cone Motility and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include Rho guanyl-nucleotide exchange factor activity. An important paralog of this gene is SPATA13.

UniProtKB/Swiss-Prot Summary for ARHGEF9 Gene

  • Acts as guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters (By similarity).

Gene Wiki entry for ARHGEF9 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ARHGEF9 Gene

Genomics for ARHGEF9 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ARHGEF9 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
GH0XJ063750 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas 612.1 +56.0 56015 5.9 SP1 CREB1 PRDM10 ZNF512 POLR2A FOS PRDM1 RELA PKNOX1 PATZ1 ARHGEF9 HSALNG0138235 MIR1468 piR-33614-285 SPIN4
GH0XJ063781 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE CraniofacialAtlas 600.3 +25.2 25234 4.5 POLR2A ZNF316 MAFF MAFK MAFG SIN3A TAF1 TBP ARHGEF9 MIR1468 piR-33804-187 SPIN4
GH0XJ063809 Promoter 0.4 EPDnew 600.7 0.0 -11 0.1 RFX5 ARHGEF9 piR-54764-683 AMER1
GH0XJ063761 Enhancer 0.8 Ensembl ENCODE 13.5 +47.5 47473 1.2 CTCF RAD21 IKZF2 TRIM22 EED ARID3A RELB RUNX3 BCLAF1 TCF12 MIR1468 ARHGEF9 BTF3P8 HSALNG0138235 SPIN4
GH0XJ063745 Enhancer 0.6 Ensembl ENCODE 12.3 +63.3 63274 4.8 RUNX3 NFIC SMARCA4 EGR2 MIR1468 ARHGEF9 HSALNG0138235 piR-33614-285 SPIN4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ARHGEF9 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ARHGEF9

Top Transcription factor binding sites by QIAGEN in the ARHGEF9 gene promoter:
  • C/EBPbeta
  • E47
  • LCR-F1
  • Meis-1
  • Meis-1a
  • Meis-1b
  • MyoD
  • PPAR-gamma1
  • PPAR-gamma2
  • Tal-1

Genomic Locations for ARHGEF9 Gene

Genomic Locations for ARHGEF9 Gene
chrX:63,634,967-63,809,274
(GRCh38/hg38)
Size:
174,308 bases
Orientation:
Minus strand
chrX:62,854,847-63,005,426
(GRCh37/hg19)
Size:
150,580 bases
Orientation:
Minus strand

Genomic View for ARHGEF9 Gene

Genes around ARHGEF9 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ARHGEF9 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ARHGEF9 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ARHGEF9 Gene

Proteins for ARHGEF9 Gene

  • Protein details for ARHGEF9 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43307-ARHG9_HUMAN
    Recommended name:
    Rho guanine nucleotide exchange factor 9
    Protein Accession:
    O43307
    Secondary Accessions:
    • A8K1S8
    • B4DHC7
    • F8W7P8
    • Q5JSL6

    Protein attributes for ARHGEF9 Gene

    Size:
    516 amino acids
    Molecular mass:
    60982 Da
    Quaternary structure:
    • Interacts with GPHN.
    SequenceCaution:
    • Sequence=BAA24854.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ARHGEF9 Gene

    Alternative splice isoforms for ARHGEF9 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ARHGEF9 Gene

Post-translational modifications for ARHGEF9 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for ARHGEF9 Gene

Domains & Families for ARHGEF9 Gene

Gene Families for ARHGEF9 Gene

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

Protein Domains for ARHGEF9 Gene

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

Suggested Antigen Peptide Sequences for ARHGEF9 Gene

GenScript: Design optimal peptide antigens:
  • Rac/Cdc42 guanine nucleotide exchange factor 9 (ARHG9_HUMAN)
  • cDNA FLJ59516, highly similar to Homo sapiens Cdc42 guanine nucleotide exchange factor (GEF) 9 (ARHGEF9), mRNA (B1AMR3_HUMAN)
  • cDNA FLJ50145, highly similar to Homo sapiens Cdc42 guanine nucleotide exchange factor (GEF) 9 (ARHGEF9), mRNA (B4DGQ8_HUMAN)
  • cDNA FLJ50765, highly similar to Homo sapiens Cdc42 guanine nucleotide exchange factor (GEF) 9 (ARHGEF9), mRNA (B4DHC7_HUMAN)
genes like me logo Genes that share domains with ARHGEF9: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for ARHGEF9 Gene

Function for ARHGEF9 Gene

Molecular function for ARHGEF9 Gene

UniProtKB/Swiss-Prot Function:
Acts as guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters (By similarity).

Phenotypes From GWAS Catalog for ARHGEF9 Gene

Gene Ontology (GO) - Molecular Function for ARHGEF9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity IEA --
GO:0005515 protein binding IEA --
genes like me logo Genes that share ontologies with ARHGEF9: view
genes like me logo Genes that share phenotypes with ARHGEF9: view

Human Phenotype Ontology for ARHGEF9 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ARHGEF9 Gene

MGI Knock Outs for ARHGEF9:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ARHGEF9

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for ARHGEF9 Gene

Localization for ARHGEF9 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ARHGEF9 Gene

Cytoplasm. Cell junction, synapse, postsynaptic density.

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 ARHGEF9 gene
Compartment Confidence
cytosol 5
plasma membrane 2
cytoskeleton 2
extracellular 1
mitochondrion 1
peroxisome 1
nucleus 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 ARHGEF9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IDA,TAS --
GO:0014069 postsynaptic density ISS --
GO:0030054 cell junction IEA --
GO:0045202 synapse IEA --
genes like me logo Genes that share ontologies with ARHGEF9: view

Pathways & Interactions for ARHGEF9 Gene

genes like me logo Genes that share pathways with ARHGEF9: view

Pathways by source for ARHGEF9 Gene

21 Qiagen pathways for ARHGEF9 Gene
  • Activation of PKC through GPCR
  • Breast Cancer Regulation by Stathmin1
  • CXCR4 Pathway
  • G-AlphaI Signaling
  • G-AlphaQ Signaling

SIGNOR curated interactions for ARHGEF9 Gene

Activates:

Gene Ontology (GO) - Biological Process for ARHGEF9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007186 G protein-coupled receptor signaling pathway TAS --
GO:0043065 positive regulation of apoptotic process TAS --
GO:0051056 regulation of small GTPase mediated signal transduction TAS --
GO:0099150 regulation of postsynaptic specialization assembly IEA --
genes like me logo Genes that share ontologies with ARHGEF9: view

Drugs & Compounds for ARHGEF9 Gene

(3) Drugs for ARHGEF9 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 ARHGEF9: view

Transcripts for ARHGEF9 Gene

mRNA/cDNA for ARHGEF9 Gene

27 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
43 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 ARHGEF9

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ARHGEF9 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b
SP1:
SP2: - -

Relevant External Links for ARHGEF9 Gene

GeneLoc Exon Structure for
ARHGEF9

Expression for ARHGEF9 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ARHGEF9 Gene

Protein differential expression in normal tissues from HIPED for ARHGEF9 Gene

This gene is overexpressed in Blymphocyte (36.3) and Platelet (25.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ARHGEF9 Gene



Protein tissue co-expression partners for ARHGEF9 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ARHGEF9

SOURCE GeneReport for Unigene cluster for ARHGEF9 Gene:

Hs.54697

mRNA Expression by UniProt/SwissProt for ARHGEF9 Gene:

O43307-ARHG9_HUMAN
Tissue specificity: Detected in brain. Detected at low levels in heart.

Evidence on tissue expression from TISSUES for ARHGEF9 Gene

  • Nervous system(4.9)
  • Eye(2.7)
  • Muscle(2.2)
  • Kidney(2.1)
  • Skin(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ARHGEF9 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
Regions:
Head and neck:
  • brain
  • head
General:
  • spinal cord
genes like me logo Genes that share expression patterns with ARHGEF9: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for ARHGEF9 Gene

Orthologs for ARHGEF9 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ARHGEF9 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ARHGEF9 30 31
  • 99.68 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ARHGEF9 30 31
  • 95.2 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia LOC537718 30
  • 94.61 (n)
ARHGEF9 31
  • 91 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia ARHGEF9 31
  • 94 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Arhgef9 30 17 31
  • 93.02 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Arhgef9 30
  • 92.97 (n)
Oppossum
(Monodelphis domestica)
Mammalia ARHGEF9 31
  • 41 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ARHGEF9 30 31
  • 84.15 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 85 (a)
OneToMany
-- 31
  • 81 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia arhgef9 30
  • 80.86 (n)
Zebrafish
(Danio rerio)
Actinopterygii arhgef9a 31
  • 79 (a)
OneToMany
arhgef9b 30 31 31
  • 76.11 (n)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.7470 31
  • 29 (a)
OneToMany
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.3922 30
Species where no ortholog for ARHGEF9 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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 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)
  • Worm (Caenorhabditis elegans)

Evolution for ARHGEF9 Gene

ENSEMBL:
Gene Tree for ARHGEF9 (if available)
TreeFam:
Gene Tree for ARHGEF9 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ARHGEF9: view image

Paralogs for ARHGEF9 Gene

(6) SIMAP similar genes for ARHGEF9 Gene using alignment to 4 proteins:

  • ARHG9_HUMAN
  • B1AMR3_HUMAN
  • B1AMR4_HUMAN
  • B4DGQ8_HUMAN
genes like me logo Genes that share paralogs with ARHGEF9: view

Variants for ARHGEF9 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ARHGEF9 Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
644871 Benign: Early infantile epileptic encephalopathy 8 63,785,117(-) A/G MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT
648941 Likely Pathogenic: Early infantile epileptic encephalopathy 8 63,697,151(-) C/T MISSENSE_VARIANT
653238 Likely Benign: Early infantile epileptic encephalopathy 8 63,638,135(-) C/G MISSENSE_VARIANT,THREE_PRIME_UTR_VARIANT
653302 Uncertain Significance: Early infantile epileptic encephalopathy 8 63,638,167(-) G/A MISSENSE_VARIANT,THREE_PRIME_UTR_VARIANT
654805 Uncertain Significance: Early infantile epileptic encephalopathy 8 63,724,666(-) G/A MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for ARHGEF9 Gene

Structural Variations from Database of Genomic Variants (DGV) for ARHGEF9 Gene

Variant ID Type Subtype PubMed ID
esv1584074 OTHER inversion 17803354
esv3558915 CNV deletion 23714750
esv3574010 CNV loss 25503493
esv3576915 CNV gain 25503493
nsv474047 CNV novel sequence insertion 20440878

Variation tolerance for ARHGEF9 Gene

Residual Variation Intolerance Score: 70.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.42; 9.31% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ARHGEF9 Gene

Human Gene Mutation Database (HGMD)
ARHGEF9
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ARHGEF9

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ARHGEF9 Gene

Disorders for ARHGEF9 Gene

MalaCards: The human disease database

(13) MalaCards diseases for ARHGEF9 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
epileptic encephalopathy, early infantile, 8
  • eiee8
hyperekplexia
  • startle disease, familial
early infantile epileptic encephalopathy
  • early infantile epileptic encephalopathy with burst-suppression
ritscher-schinzel syndrome 2
  • rtsc2
epilepsy
  • epilepsy syndrome
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

ARHG9_HUMAN
  • Epileptic encephalopathy, early infantile, 8 (EIEE8) [MIM:300607]: A disorder characterized by hyperekplexia and early infantile epileptic encephalopathy. Neurologic features include exaggerated startle response, seizures, impaired psychomotor development, and mental retardation. Seizures can be provoked by tactile stimulation or extreme emotion. {ECO:0000269 PubMed:15215304, ECO:0000269 PubMed:22612257, ECO:0000269 PubMed:25678704}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for ARHGEF9

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 ARHGEF9: view

No data available for Genatlas for ARHGEF9 Gene

Publications for ARHGEF9 Gene

  1. The GDP-GTP exchange factor collybistin: an essential determinant of neuronal gephyrin clustering. (PMID: 15215304) Harvey K … Harvey RJ (The Journal of neuroscience : the official journal of the Society for Neuroscience 2004) 3 4 23
  2. Identification and characterization of hPEM-2, a guanine nucleotide exchange factor specific for Cdc42. (PMID: 10559246) Reid T … Collard JG (The Journal of biological chemistry 1999) 2 3 4
  3. Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro. (PMID: 9455477) Ishikawa K … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1997) 2 3 4
  4. Lipid binding defects and perturbed synaptogenic activity of a Collybistin R290H mutant that causes epilepsy and intellectual disability. (PMID: 25678704) Papadopoulos T … Brose N (The Journal of biological chemistry 2015) 3 4
  5. Mutation of ARHGAP9 in patients with coronary spastic angina. (PMID: 19911011) Takefuji M … Kaibuchi K (Journal of human genetics 2010) 3 41

Products for ARHGEF9 Gene

  • Signalway Proteins for ARHGEF9

Sources for ARHGEF9 Gene