Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli working through G protein-coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein has been observed to form a myeloid/lymphoid fusion partner in acute myeloid leukemia. Three transcript variants encodi... See more...

Aliases for ARHGEF12 Gene

Aliases for ARHGEF12 Gene

  • Rho Guanine Nucleotide Exchange Factor 12 2 3 3 4 5
  • Rho Guanine Nucleotide Exchange Factor (GEF) 12 2 3
  • Leukemia-Associated RhoGEF 3 4
  • LARG 3 4
  • Leukemia-Associated Rho Guanine Nucleotide Exchange Factor 3
  • KIAA0382 4
  • PRO2792 3

External Ids for ARHGEF12 Gene

Previous GeneCards Identifiers for ARHGEF12 Gene

  • GC11P122207
  • GC11P121719
  • GC11P120241
  • GC11P119745
  • GC11P119712
  • GC11P116148
  • GC11P120207

Summaries for ARHGEF12 Gene

Entrez Gene Summary for ARHGEF12 Gene

  • Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli working through G protein-coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein has been observed to form a myeloid/lymphoid fusion partner in acute myeloid leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

GeneCards Summary for ARHGEF12 Gene

ARHGEF12 (Rho Guanine Nucleotide Exchange Factor 12) is a Protein Coding gene. Diseases associated with ARHGEF12 include Giant Axonal Neuropathy and Acalculous Cholecystitis. Among its related pathways are Oxytocin signaling pathway and RET signaling. Gene Ontology (GO) annotations related to this gene include GTPase activator activity and G protein-coupled receptor binding. An important paralog of this gene is ARHGEF11.

UniProtKB/Swiss-Prot Summary for ARHGEF12 Gene

  • May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13.

Gene Wiki entry for ARHGEF12 Gene

Additional gene information for ARHGEF12 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ARHGEF12 Gene

Genomics for ARHGEF12 Gene

GeneHancer (GH) Regulatory Elements for ARHGEF12 Gene

Promoters and enhancers for ARHGEF12 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
GH11J120334 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 755.4 +1.9 1939 8.5 GTF3C2 ZNF785 SP1 ZBTB40 CTCF ZBTB6 LCORL FOXA1 RBPJ SMARCE1 ARHGEF12 TLCD5 TECTA ENSG00000274303
GH11J120390 Promoter/Enhancer 1.3 EPDnew Ensembl ENCODE 760.9 +55.2 55195 3.2 RBPJ MIXL1 NFYC HLF ELF3 ZNF644 KAT8 GATAD2A SP1 SOX13 ARHGEF12 TLCD5 TBCEL BMPR1AP2 piR-57461-038 GRIK4
GH11J120385 Promoter 0.6 EPDnew 760.8 +48.9 48906 0.1 MLLT1 POLR2A VEZF1 ARHGEF12 piR-57461-038 GRIK4
GH11J120430 Enhancer 1 FANTOM5 ENCODE 14.8 +95.8 95780 2.8 SMARCE1 CC2D1A DACH1 TEAD4 SP7 ZSCAN21 SMARCA4 ZBTB33 DPF2 IKZF1 ARHGEF12 TLCD5 OAF piR-57461-038 GRIK4
GH11J120371 Enhancer 0.7 Ensembl ENCODE 15.8 +36.0 35969 2.3 CREB1 MIXL1 HLF GATAD2A SAP130 NFIL3 HNF4A PRDM6 FOXA3 ARHGEF12 TLCD5 ENSG00000274303 piR-57461-038
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ARHGEF12 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ARHGEF12 gene promoter:
  • AML1a

Genomic Locations for ARHGEF12 Gene

Genomic Locations for ARHGEF12 Gene
chr11:120,336,406-120,489,937
(GRCh38/hg38)
Size:
153,532 bases
Orientation:
Plus strand
chr11:120,207,618-120,360,645
(GRCh37/hg19)
Size:
153,028 bases
Orientation:
Plus strand

Genomic View for ARHGEF12 Gene

Genes around ARHGEF12 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ARHGEF12 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ARHGEF12 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ARHGEF12 Gene

Proteins for ARHGEF12 Gene

  • Protein details for ARHGEF12 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NZN5-ARHGC_HUMAN
    Recommended name:
    Rho guanine nucleotide exchange factor 12
    Protein Accession:
    Q9NZN5
    Secondary Accessions:
    • O15086
    • Q6P526

    Protein attributes for ARHGEF12 Gene

    Size:
    1544 amino acids
    Molecular mass:
    173232 Da
    Quaternary structure:
    • Interacts with GNA12 and GNA13, probably through the RGS-like domain. Interacts with RHOA, PLXNB1 and PLXNB2. Interacts through its PDZ domain with IGF1R beta subunit. Interacts with GCSAM.
    SequenceCaution:
    • Sequence=AAH63117.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ARHGEF12 Gene

    Alternative splice isoforms for ARHGEF12 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ARHGEF12 Gene

Post-translational modifications for ARHGEF12 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for ARHGEF12 Gene

Domains & Families for ARHGEF12 Gene

Gene Families for ARHGEF12 Gene

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

Suggested Antigen Peptide Sequences for ARHGEF12 Gene

GenScript: Design optimal peptide antigens:
  • Leukemia-associated RhoGEF (ARHGC_HUMAN)
genes like me logo Genes that share domains with ARHGEF12: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for ARHGEF12 Gene

Function for ARHGEF12 Gene

Molecular function for ARHGEF12 Gene

UniProtKB/Swiss-Prot Function:
May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13.

Phenotypes From GWAS Catalog for ARHGEF12 Gene

Gene Ontology (GO) - Molecular Function for ARHGEF12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001664 G protein-coupled receptor binding IDA 15755723
GO:0005085 guanyl-nucleotide exchange factor activity IEA --
GO:0005089 Rho guanyl-nucleotide exchange factor activity IEA --
GO:0005096 GTPase activator activity IEA --
GO:0005515 protein binding IEA,IPI 11724822
genes like me logo Genes that share ontologies with ARHGEF12: view
genes like me logo Genes that share phenotypes with ARHGEF12: view

Animal Models for ARHGEF12 Gene

MGI Knock Outs for ARHGEF12:

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ARHGEF12 Gene

Localization for ARHGEF12 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ARHGEF12 Gene

Cytoplasm. Membrane. Note=Translocated to the membrane upon stimulation. {ECO:0000305}.

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 ARHGEF12 gene
Compartment Confidence
cytosol 5
nucleus 4
plasma membrane 3
extracellular 1
cytoskeleton 1
mitochondrion 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoplasm (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ARHGEF12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA,IEA 15755723
GO:0005829 cytosol TAS --
GO:0016020 membrane IEA --
GO:0070062 extracellular exosome HDA 19056867
genes like me logo Genes that share ontologies with ARHGEF12: view

Pathways & Interactions for ARHGEF12 Gene

PathCards logo

SuperPathways for ARHGEF12 Gene

genes like me logo Genes that share pathways with ARHGEF12: view

SIGNOR curated interactions for ARHGEF12 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for ARHGEF12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007186 G protein-coupled receptor signaling pathway TAS,IEA --
GO:0007266 Rho protein signal transduction IEA --
GO:0035023 regulation of Rho protein signal transduction IEA --
GO:0035556 intracellular signal transduction IEA --
GO:0043065 positive regulation of apoptotic process TAS --
genes like me logo Genes that share ontologies with ARHGEF12: view

Drugs & Compounds for ARHGEF12 Gene

(6) Drugs for ARHGEF12 Gene - From: HMDB and Novoseek

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

(3) Additional Compounds for ARHGEF12 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ARHGEF12: view

Transcripts for ARHGEF12 Gene

mRNA/cDNA for ARHGEF12 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ARHGEF12 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^
SP1: - -
SP2: - - -
SP3:
SP4:

ExUns: 24 ^ 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32 ^ 33 ^ 34 ^ 35 ^ 36 ^ 37 ^ 38 ^ 39
SP1:
SP2:
SP3:
SP4:

Relevant External Links for ARHGEF12 Gene

GeneLoc Exon Structure for
ARHGEF12
ECgene alternative splicing isoforms for
ARHGEF12

Expression for ARHGEF12 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ARHGEF12 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for ARHGEF12 Gene

This gene is overexpressed in Brain (12.8), Pancreas (6.7), and Peripheral blood mononuclear cells (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ARHGEF12 Gene



Protein tissue co-expression partners for ARHGEF12 Gene

NURSA nuclear receptor signaling pathways regulating expression of ARHGEF12 Gene:

ARHGEF12

SOURCE GeneReport for Unigene cluster for ARHGEF12 Gene:

Hs.24598

mRNA Expression by UniProt/SwissProt for ARHGEF12 Gene:

Q9NZN5-ARHGC_HUMAN
Tissue specificity: Ubiquitously expressed. Isoform 2 is found in jejunum and testis.

Evidence on tissue expression from TISSUES for ARHGEF12 Gene

  • Nervous system(4.9)
  • Blood(4.6)
  • Liver(4.6)
  • Thyroid gland(4.3)
  • Kidney(2.9)
  • Heart(2.8)
  • Muscle(2.8)
  • Eye(2.5)
  • Lung(2.3)
  • Intestine(2.1)
genes like me logo Genes that share expression patterns with ARHGEF12: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for ARHGEF12 Gene

Orthologs for ARHGEF12 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ARHGEF12 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ARHGEF12 33 32
  • 99.72 (n)
OneToOne
cow
(Bos Taurus)
Mammalia ARHGEF12 33 32
  • 91.21 (n)
OneToOne
dog
(Canis familiaris)
Mammalia ARHGEF12 33 32
  • 91.21 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Arhgef12 17 33 32
  • 87.82 (n)
rat
(Rattus norvegicus)
Mammalia Arhgef12 32
  • 86.87 (n)
oppossum
(Monodelphis domestica)
Mammalia ARHGEF12 33
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ARHGEF12 33
  • 80 (a)
OneToOne
chicken
(Gallus gallus)
Aves ARHGEF12 33 32
  • 72.99 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ARHGEF12 33
  • 72 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia arhgef12 32
  • 66 (n)
Str.1176 32
African clawed frog
(Xenopus laevis)
Amphibia Larg 32
zebrafish
(Danio rerio)
Actinopterygii arhgef12 32
  • 60.58 (n)
ARHGEF12 (1 of 2) 33
  • 52 (a)
OneToMany
arhgef12b 33
  • 49 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta RhoGEF2 33 34
  • 15 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea F13E6.6 34
  • 37 (a)
rhgf-1 33
  • 26 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ROM1 33
  • 13 (a)
ManyToMany
ROM2 33
  • 13 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 24 (a)
OneToMany
Species where no ortholog for ARHGEF12 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • 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 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 ARHGEF12 Gene

ENSEMBL:
Gene Tree for ARHGEF12 (if available)
TreeFam:
Gene Tree for ARHGEF12 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ARHGEF12: view image

Paralogs for ARHGEF12 Gene

(4) SIMAP similar genes for ARHGEF12 Gene using alignment to 2 proteins:

  • ARHGC_HUMAN
  • E9PMR6_HUMAN
genes like me logo Genes that share paralogs with ARHGEF12: view

Variants for ARHGEF12 Gene

Sequence variations from dbSNP and Humsavar for ARHGEF12 Gene

SNP ID Clin Chr 11 pos Variation AA Info Type
rs1000019660 -- 120,457,412(+) T/G intron_variant
rs1000027167 -- 120,487,635(+) A/G 3_prime_UTR_variant
rs1000030358 -- 120,337,660(+) C/T 5_prime_UTR_variant, genic_upstream_transcript_variant, intron_variant
rs1000033652 -- 120,388,143(+) T/C intron_variant
rs1000037186 -- 120,346,842(+) A/C/G genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for ARHGEF12 Gene

Variant ID Type Subtype PubMed ID
dgv1287n100 CNV loss 25217958
dgv1288n100 CNV loss 25217958
esv2676644 CNV deletion 23128226
esv3627902 CNV loss 21293372
esv6844 CNV gain 19470904
nsv1050935 CNV gain 25217958
nsv1051672 CNV loss 25217958
nsv1051783 CNV gain 25217958
nsv471840 CNV novel sequence insertion 20440878
nsv519 CNV insertion 18451855
nsv520 CNV insertion 18451855
nsv529003 CNV loss 19592680

Variation tolerance for ARHGEF12 Gene

Residual Variation Intolerance Score: 3.12% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.41; 71.24% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ARHGEF12 Gene

Human Gene Mutation Database (HGMD)
ARHGEF12
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ARHGEF12

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ARHGEF12 Gene

Disorders for ARHGEF12 Gene

MalaCards: The human disease database

(3) MalaCards diseases for ARHGEF12 Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
giant axonal neuropathy
  • gan1
acalculous cholecystitis
  • acute acalculous cholecystitis
leukemia
  • leukemias
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

ARHGC_HUMAN
  • Note=A chromosomal aberration involving ARHGEF12 may be a cause of acute leukemia. Translocation t(11;11)(q23;23) with KMT2A/MLL1. {ECO:0000269 PubMed:10681437}.

Additional Disease Information for ARHGEF12

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with ARHGEF12: view

No data available for Genatlas for ARHGEF12 Gene

Publications for ARHGEF12 Gene

  1. Conformational change upon ligand binding and dynamics of the PDZ domain from leukemia-associated Rho guanine nucleotide exchange factor. (PMID: 18411422) Liu J … Shi Y (Protein science : a publication of the Protein Society 2008) 3 4 23 56
  2. Genetic variants in the leukemia-associated Rho guanine nucleotide exchange factor (ARHGEF12) gene are not associated with T2DM and related parameters in Caucasians (KORA study). (PMID: 17766704) Holzapfel C … Illig T (European journal of endocrinology 2007) 3 23 43 56
  3. A functional Tyr1306Cys variant in LARG is associated with increased insulin action in vivo. (PMID: 16644711) Kovacs P … Baier LJ (Diabetes 2006) 3 23 43 56
  4. Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor. (PMID: 15331592) Kristelly R … Tesmer JJ (The Journal of biological chemistry 2004) 3 4 23 56
  5. Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF. (PMID: 12183458) Perrot V … Gutkind JS (The Journal of biological chemistry 2002) 3 4 23 56

Products for ARHGEF12 Gene

Sources for ARHGEF12 Gene