This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins belonging to the RAS superfamily. The protein encoded by the orthologous gene in rat is localized to the Golgi complex and can redistribute to microtubules. The rat protein stimulates the activity of some Rho GTPases in vitro. Genomic deletions of this g... See more...

Aliases for ARHGAP4 Gene

Aliases for ARHGAP4 Gene

  • Rho GTPase Activating Protein 4 2 3 5
  • Rho-GAP Hematopoietic Protein C1 2 3 4
  • P115 2 3 4
  • Rho-Type GTPase-Activating Protein 4 3 4
  • Rho GTPase-Activating Protein 4 3 4
  • KIAA0131 2 4
  • RhoGAP4 2 3
  • SrGAP4 2 3
  • RGC1 3 4
  • C1 2 3
  • ARHGAP4 5
  • RHOGAP4 4

External Ids for ARHGAP4 Gene

Previous GeneCards Identifiers for ARHGAP4 Gene

  • GC0XM147310
  • GC0XM149627
  • GC0XM150758
  • GC0XM151640
  • GC0XM152693
  • GC0XM152826
  • GC0XM153172
  • GC0XM141824

Summaries for ARHGAP4 Gene

Entrez Gene Summary for ARHGAP4 Gene

  • This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins belonging to the RAS superfamily. The protein encoded by the orthologous gene in rat is localized to the Golgi complex and can redistribute to microtubules. The rat protein stimulates the activity of some Rho GTPases in vitro. Genomic deletions of this gene and a neighboring gene have been found in patients with nephrogenic diabetes insipidus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

GeneCards Summary for ARHGAP4 Gene

ARHGAP4 (Rho GTPase Activating Protein 4) is a Protein Coding gene. Diseases associated with ARHGAP4 include Diabetes Insipidus, Nephrogenic, Autosomal and Diabetes Insipidus. Among its related pathways are Signaling by GPCR and Actin Nucleation by ARP-WASP Complex. Gene Ontology (GO) annotations related to this gene include GTPase activator activity and Rac GTPase binding. An important paralog of this gene is SRGAP3.

UniProtKB/Swiss-Prot Summary for ARHGAP4 Gene

  • Inhibitory effect on stress fiber organization. May down-regulate Rho-like GTPase in hematopoietic cells.

Gene Wiki entry for ARHGAP4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ARHGAP4 Gene

Genomics for ARHGAP4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ARHGAP4 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
GH0XJ153921 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 600.4 +9.0 8994 9.3 ARHGAP35 SP1 HNRNPL PRDM10 IKZF1 CTCF ZNF692 POLR2A BACH1 LARP7 RF00017-8806 ARHGAP4 TMEM187 HCFC1 FLNA EMD SLC10A3 HCFC1-AS1 SNORA70 DKC1
GH0XJ153933 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas 600.7 +0.2 198 2.8 SP1 CREB1 BACH1 LARP7 RBFOX2 POLR2A NR2C1 TRIM22 HDAC1 ELK1 ARHGAP4 NAA10 lnc-ARHGAP4-1 lnc-RENBP-1 TMEM187 ENSG00000261773 ENSG00000260081 RENBP ENSG00000284987
GH0XJ153909 Promoter/Enhancer 0.7 EPDnew Ensembl 600.3 +25.6 25608 0.4 HDGF ZNF687 GLIS2 ENSG00000284987 lnc-L1CAM-1 ARHGAP4
GH0XJ153907 Promoter 0.3 EPDnew 600.3 +27.0 27035 0.1 ENSG00000284987 lnc-L1CAM-1 ARHGAP4 IKBKG AVPR2
GH0XJ153884 Promoter/Enhancer 1.6 EPDnew FANTOM5 Ensembl ENCODE 12.5 +48.9 48894 3 CTCF ZIC2 POLR2A EZH2 KLF9 RAD21 KLF7 GATAD2A ZBTB48 ZBTB26 L1CAM RENBP TMEM187 PDZD4 IDH3G SSR4 SRPK3 PLXNB3 NAA10 ARHGAP4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ARHGAP4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ARHGAP4

Top Transcription factor binding sites by QIAGEN in the ARHGAP4 gene promoter:
  • AML1a
  • AP-1
  • ARP-1
  • E47
  • Elk-1
  • Ik-3
  • NF-1
  • NF-1/L
  • Pax-5
  • Tal-1beta

Genomic Locations for ARHGAP4 Gene

Genomic Locations for ARHGAP4 Gene
chrX:153,907,367-153,934,999
(GRCh38/hg38)
Size:
27,633 bases
Orientation:
Minus strand
chrX:153,172,821-153,200,452
(GRCh37/hg19)
Size:
27,632 bases
Orientation:
Minus strand

Genomic View for ARHGAP4 Gene

Genes around ARHGAP4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ARHGAP4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ARHGAP4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ARHGAP4 Gene

Proteins for ARHGAP4 Gene

  • Protein details for ARHGAP4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P98171-RHG04_HUMAN
    Recommended name:
    Rho GTPase-activating protein 4
    Protein Accession:
    P98171
    Secondary Accessions:
    • Q14144
    • Q86UY3

    Protein attributes for ARHGAP4 Gene

    Size:
    946 amino acids
    Molecular mass:
    105026 Da
    Quaternary structure:
    • Interacts with NCKAP1L.

    Three dimensional structures from OCA and Proteopedia for ARHGAP4 Gene

    Alternative splice isoforms for ARHGAP4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ARHGAP4 Gene

Post-translational modifications for ARHGAP4 Gene

  • Ubiquitination at Lys443
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for ARHGAP4 Gene

Domains & Families for ARHGAP4 Gene

Gene Families for ARHGAP4 Gene

Protein Domains for ARHGAP4 Gene

InterPro:
Blocks:
  • RhoGAP domain
  • SH3 domain signature
  • Cdc15/Fes/CIP4
ProtoNet:

Suggested Antigen Peptide Sequences for ARHGAP4 Gene

GenScript: Design optimal peptide antigens:
  • ARHGAP4 protein (Q6PJ34_HUMAN)
  • p115 (RHG04_HUMAN)
genes like me logo Genes that share domains with ARHGAP4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for ARHGAP4 Gene

Function for ARHGAP4 Gene

Molecular function for ARHGAP4 Gene

UniProtKB/Swiss-Prot Function:
Inhibitory effect on stress fiber organization. May down-regulate Rho-like GTPase in hematopoietic cells.
GENATLAS Biochemistry:
Rho GTPase activating protein 4,155kDa,aplysia related,involved in signal transduction

Phenotypes From GWAS Catalog for ARHGAP4 Gene

Gene Ontology (GO) - Molecular Function for ARHGAP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005070 SH3/SH2 adaptor activity TAS --
GO:0005096 GTPase activator activity IEA --
GO:0005515 protein binding IEA,IPI 16417406
GO:0048365 Rac GTPase binding IBA 21873635
genes like me logo Genes that share ontologies with ARHGAP4: view
genes like me logo Genes that share phenotypes with ARHGAP4: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ARHGAP4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for ARHGAP4 Gene

Localization for ARHGAP4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ARHGAP4 Gene

Cytoplasm. Note=Just below the plasma membrane.

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 ARHGAP4 gene
Compartment Confidence
cytosol 5
nucleus 4
cytoskeleton 3
golgi apparatus 3
plasma membrane 1
extracellular 1
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Focal adhesion sites (2)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ARHGAP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm TAS,IDA --
GO:0005794 Golgi apparatus IEA --
GO:0005829 cytosol TAS --
GO:0005874 microtubule IEA --
GO:0030426 growth cone IEA --
genes like me logo Genes that share ontologies with ARHGAP4: view

Pathways & Interactions for ARHGAP4 Gene

PathCards logo

SuperPathways for ARHGAP4 Gene

SuperPathway Contained pathways
1 G12-G13 in Cellular Signaling
-
2 Actin Nucleation by ARP-WASP Complex
.35
3 RhoGDI Pathway
.33
4 p75 NTR receptor-mediated signalling
5 Signaling by GPCR
genes like me logo Genes that share pathways with ARHGAP4: view

Pathways by source for ARHGAP4 Gene

1 BioSystems pathway for ARHGAP4 Gene
3 Reactome pathways for ARHGAP4 Gene
3 Qiagen pathways for ARHGAP4 Gene
  • G12-G13 in Cellular Signaling
  • RhoA Pathway
  • RhoGDI Pathway
1 GeneTex pathway for ARHGAP4 Gene

SIGNOR curated interactions for ARHGAP4 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for ARHGAP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007010 cytoskeleton organization TAS 8570618
GO:0007165 signal transduction IEA --
GO:0007266 Rho protein signal transduction TAS 8570618
GO:0007399 nervous system development IEA --
GO:0009967 positive regulation of signal transduction IEA --
genes like me logo Genes that share ontologies with ARHGAP4: view

Drugs & Compounds for ARHGAP4 Gene

(1) Drugs for ARHGAP4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for ARHGAP4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ARHGAP4: view

Transcripts for ARHGAP4 Gene

mRNA/cDNA for ARHGAP4 Gene

2 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
24 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 ARHGAP4

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ARHGAP4 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6a · 6b ^ 7a · 7b · 7c ^ 8 ^ 9a · 9b · 9c ^ 10a · 10b · 10c · 10d ^ 11a · 11b ^ 12 ^ 13a · 13b ^
SP1: - - - - - -
SP2: - - - - - - -
SP3: - - - - - - -
SP4: - - - - - - -
SP5:
SP6: - - -
SP7:
SP8:
SP9: - - -
SP10: - - - -
SP11: - - - -
SP12: - -
SP13:
SP14:
SP15:
SP16: -
SP17:
SP18:

ExUns: 14a · 14b ^ 15 ^ 16a · 16b ^ 17 ^ 18a · 18b ^ 19a · 19b ^ 20 ^ 21a · 21b ^ 22 ^ 23a · 23b ^ 24a · 24b ^ 25 ^ 26a · 26b
SP1: - - - -
SP2: - - - -
SP3: - - - - - - -
SP4:
SP5: - - - -
SP6:
SP7: - - -
SP8: -
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:

Relevant External Links for ARHGAP4 Gene

GeneLoc Exon Structure for
ARHGAP4

Expression for ARHGAP4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ARHGAP4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ARHGAP4 Gene

This gene is overexpressed in Whole Blood (x16.4) and Spleen (x7.1).

Protein differential expression in normal tissues from HIPED for ARHGAP4 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (19.3), Lymph node (19.3), and Monocytes (6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ARHGAP4 Gene



Protein tissue co-expression partners for ARHGAP4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ARHGAP4

SOURCE GeneReport for Unigene cluster for ARHGAP4 Gene:

Hs.701324

mRNA Expression by UniProt/SwissProt for ARHGAP4 Gene:

P98171-RHG04_HUMAN
Tissue specificity: Predominantly in hematopoietic cells (spleen, thymus and leukocytes); low levels in placenta, lung and various fetal tissues.

Evidence on tissue expression from TISSUES for ARHGAP4 Gene

  • Bone marrow(4.6)
  • Liver(4.3)
  • Pancreas(4.3)
  • Lymph node(2.7)
  • Spleen(2.7)
  • Nervous system(2.3)
  • Blood(2)
genes like me logo Genes that share expression patterns with ARHGAP4: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ARHGAP4 Gene

Orthologs for ARHGAP4 Gene

This gene was present in the common ancestor of animals.

Orthologs for ARHGAP4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ARHGAP4 30 31
  • 99.66 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ARHGAP4 30 31
  • 87.92 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ARHGAP4 30 31
  • 85.15 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Arhgap4 30
  • 81.34 (n)
Mouse
(Mus musculus)
Mammalia Arhgap4 30 17 31
  • 80.7 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia ARHGAP4 31
  • 66 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia ARHGAP4 31
  • 66 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ARHGAP4 31
  • 57 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia arhgap4 30
  • 57.7 (n)
Zebrafish
(Danio rerio)
Actinopterygii arhgap4b 30 31
  • 56.33 (n)
OneToMany
arhgap4a 31
  • 40 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea F12F6.5 32
  • 32 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 32 (a)
OneToMany
Species where no ortholog for ARHGAP4 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)
  • 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 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 ARHGAP4 Gene

ENSEMBL:
Gene Tree for ARHGAP4 (if available)
TreeFam:
Gene Tree for ARHGAP4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ARHGAP4: view image

Paralogs for ARHGAP4 Gene

Paralogs for ARHGAP4 Gene

(16) SIMAP similar genes for ARHGAP4 Gene using alignment to 14 proteins:

  • RHG04_HUMAN
  • C9J5M2_HUMAN
  • C9JLA8_HUMAN
  • E7EQN5_HUMAN
  • E9PCM6_HUMAN
  • F5GZW3_HUMAN
  • F8WAR0_HUMAN
  • H7C120_HUMAN
  • H7C2Z8_HUMAN
  • H7C3G3_HUMAN
  • H7C3K8_HUMAN
  • Q6PJ34_HUMAN
  • S4R314_HUMAN
  • S4R352_HUMAN
genes like me logo Genes that share paralogs with ARHGAP4: view

Variants for ARHGAP4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ARHGAP4 Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
711791 Benign: not provided 153,910,547(-) C/T SYNONYMOUS_VARIANT
714975 Benign: not provided 153,913,445(-) G/A SYNONYMOUS_VARIANT
715925 Likely Benign: not provided 153,918,932(-) G/A MISSENSE_VARIANT
744647 Likely Benign: not provided 153,921,640(-) G/T SYNONYMOUS_VARIANT
771947 Benign: not provided 153,909,539(-) C/T INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for ARHGAP4 Gene

Structural Variations from Database of Genomic Variants (DGV) for ARHGAP4 Gene

Variant ID Type Subtype PubMed ID
esv33199 CNV gain+loss 17666407
nsv469867 CNV loss 16826518

Variation tolerance for ARHGAP4 Gene

Residual Variation Intolerance Score: 36.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.88; 59.09% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ARHGAP4 Gene

Human Gene Mutation Database (HGMD)
ARHGAP4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ARHGAP4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ARHGAP4 Gene

Disorders for ARHGAP4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for ARHGAP4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
diabetes insipidus, nephrogenic, autosomal
  • diabetes insipidus, nephrogenic, type ii
diabetes insipidus
familial hypocalciuric hypercalcemia
  • fhh
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for ARHGAP4

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 ARHGAP4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ARHGAP4 Gene

Publications for ARHGAP4 Gene

  1. An X chromosome-linked gene encoding a protein with characteristics of a rhoGAP predominantly expressed in hematopoietic cells. (PMID: 8570618) Tribioli C … Pelicci P (Proceedings of the National Academy of Sciences of the United States of America 1996) 2 3 4 23
  2. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  3. Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes. (PMID: 18489790) Fujimoto M … Noguchi E (BMC medical genetics 2008) 3 23
  4. Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis. (PMID: 16417406) Weiner OD … Kirschner MW (PLoS biology 2006) 3 4
  5. FNBP2 gene on human chromosome 1q32.1 encodes ARHGAP family protein with FCH, FBH, RhoGAP and SH3 domains. (PMID: 12736724) Katoh M … Katoh M (International journal of molecular medicine 2003) 3 23

Products for ARHGAP4 Gene

Sources for ARHGAP4 Gene