Human Gene ARHGEF12 (ENST00000397843.7_6) from GENCODE V47lift37
  Description: Rho guanine nucleotide exchange factor 12, transcript variant 1 (from RefSeq NM_015313.3)
Gencode Transcript: ENST00000397843.7_6
Gencode Gene: ENSG00000196914.9_8
Transcript (Including UTRs)
   Position: hg19 chr11:120,207,122-120,360,646 Size: 153,525 Total Exon Count: 41 Strand: +
Coding Region
   Position: hg19 chr11:120,207,953-120,355,786 Size: 147,834 Coding Exon Count: 41 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:120,207,122-120,360,646)mRNA (may differ from genome)Protein (1544 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGeneCardsHGNC
MalacardsMGIOMIMPubMedReactomeUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ARHGC_HUMAN
DESCRIPTION: RecName: Full=Rho guanine nucleotide exchange factor 12; AltName: Full=Leukemia-associated RhoGEF;
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.
SUBUNIT: 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.
SUBCELLULAR LOCATION: Cytoplasm (Probable). Membrane (Probable). Note=Translocated to the membrane upon stimulation (Probable).
TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 2 is found in jejunum and testis.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
DISEASE: Note=A chromosomal aberration involving ARHGEF12 may be a cause of acute leukemia. Translocation t(11;11)(q23;23) with MLL.
SIMILARITY: Contains 1 DH (DBL-homology) domain.
SIMILARITY: Contains 1 PDZ (DHR) domain.
SIMILARITY: Contains 1 PH domain.
SIMILARITY: Contains 1 RGSL (RGS-like) domain.
SEQUENCE CAUTION: Sequence=AAH63117.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/LARGID243.html";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: ARHGEF12
Diseases sorted by gene-association score: leukemia, acute myeloid* (19), shwachman-diamond syndrome (13), acalculous cholecystitis (6), giant axonal neuropathy (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 30.58 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 869.30 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -393.10831-0.473 Picture PostScript Text
3' UTR -1313.904860-0.270 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000219 - DH-domain
IPR001331 - GDS_CDC24_CS
IPR001478 - PDZ
IPR011993 - PH_like_dom
IPR001849 - Pleckstrin_homology
IPR015212 - Regulat_G_prot_signal-like
IPR016137 - Regulat_G_prot_signal_superfam
IPR015721 - RhoGEF-like

Pfam Domains:
PF00595 - PDZ domain
PF00621 - RhoGEF domain
PF09128 - Regulator of G protein signalling-like domain
PF17820 - PDZ domain
PF17838 - PH domain

SCOP Domains:
48065 - DBL homology domain (DH-domain)
48097 - Regulator of G-protein signaling, RGS
50156 - PDZ domain-like
50729 - PH domain-like
55486 - Metalloproteases ("zincins"), catalytic domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1TXD - X-ray MuPIT 1X86 - X-ray MuPIT 2OMJ - NMR MuPIT 2OS6 - NMR MuPIT


ModBase Predicted Comparative 3D Structure on Q9NZN5
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologGenome BrowserNo ortholog
Gene DetailsGene Details  Gene Details 
Gene SorterGene Sorter  Gene Sorter 
 RGDEnsembl WormBase 
    Protein Sequence 
    Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001664 G-protein coupled receptor binding
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005089 Rho guanyl-nucleotide exchange factor activity
GO:0005096 GTPase activator activity
GO:0005515 protein binding

Biological Process:
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007266 Rho protein signal transduction
GO:0035023 regulation of Rho protein signal transduction
GO:0035556 intracellular signal transduction
GO:0043065 positive regulation of apoptotic process
GO:0043547 positive regulation of GTPase activity
GO:0051056 regulation of small GTPase mediated signal transduction

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016020 membrane
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  BX648515 - Homo sapiens mRNA; cDNA DKFZp686O2372 (from clone DKFZp686O2372).
AK304316 - Homo sapiens cDNA FLJ60405 partial cds, highly similar to Rho guanine nucleotide exchange factor 12.
LF213950 - JP 2014500723-A/21453: Polycomb-Associated Non-Coding RNAs.
LF384540 - JP 2014500723-A/192043: Polycomb-Associated Non-Coding RNAs.
LP895814 - Sequence 678 from Patent EP3253886.
BC152900 - Synthetic construct Homo sapiens clone IMAGE:100016177, MGC:184137 Rho guanine nucleotide exchange factor (GEF) 12 (ARHGEF12) mRNA, encodes complete protein.
AF180681 - Homo sapiens guanine nucleotide exchange factor (LARG) mRNA, complete cds.
AB527392 - Synthetic construct DNA, clone: pF1KA0382, Homo sapiens ARHGEF12 gene for Rho guanine nucleotide exchange factor (GEF) 12, without stop codon, in Flexi system.
BX647785 - Homo sapiens mRNA; cDNA DKFZp686O2486 (from clone DKFZp686O2486).
AK294803 - Homo sapiens cDNA FLJ51627 complete cds, highly similar to Rho guanine nucleotide exchange factor 12.
AB002380 - Homo sapiens KIAA0382 mRNA for KIAA0382 protein.
MA449527 - JP 2018138019-A/21453: Polycomb-Associated Non-Coding RNAs.
MA620117 - JP 2018138019-A/192043: Polycomb-Associated Non-Coding RNAs.
BC063117 - Homo sapiens Rho guanine nucleotide exchange factor (GEF) 12, mRNA (cDNA clone IMAGE:30353240), partial cds.
AL137456 - Homo sapiens mRNA; cDNA DKFZp564O0772 (from clone DKFZp564O0772).
AF119898 - Homo sapiens PRO2792 mRNA, complete cds.
JD112710 - Sequence 93734 from Patent EP1572962.
JD459342 - Sequence 440366 from Patent EP1572962.
JD144858 - Sequence 125882 from Patent EP1572962.
JD064143 - Sequence 45167 from Patent EP1572962.
JD046843 - Sequence 27867 from Patent EP1572962.
JD344491 - Sequence 325515 from Patent EP1572962.
JD498905 - Sequence 479929 from Patent EP1572962.
JD065597 - Sequence 46621 from Patent EP1572962.
JD178305 - Sequence 159329 from Patent EP1572962.
JD467950 - Sequence 448974 from Patent EP1572962.
JD338290 - Sequence 319314 from Patent EP1572962.
JD487017 - Sequence 468041 from Patent EP1572962.
JD277565 - Sequence 258589 from Patent EP1572962.
JD355919 - Sequence 336943 from Patent EP1572962.
JD344966 - Sequence 325990 from Patent EP1572962.
JD495059 - Sequence 476083 from Patent EP1572962.
JD132960 - Sequence 113984 from Patent EP1572962.
JD060350 - Sequence 41374 from Patent EP1572962.
JD224078 - Sequence 205102 from Patent EP1572962.
JD509995 - Sequence 491019 from Patent EP1572962.
JD303714 - Sequence 284738 from Patent EP1572962.
JD363525 - Sequence 344549 from Patent EP1572962.
BC031784 - Homo sapiens Rho guanine nucleotide exchange factor (GEF) 12, mRNA (cDNA clone IMAGE:4538083), with apparent retained intron.
JD137759 - Sequence 118783 from Patent EP1572962.
JD126972 - Sequence 107996 from Patent EP1572962.
JD554431 - Sequence 535455 from Patent EP1572962.
JD080805 - Sequence 61829 from Patent EP1572962.
JD347864 - Sequence 328888 from Patent EP1572962.
JD224069 - Sequence 205093 from Patent EP1572962.
JD454426 - Sequence 435450 from Patent EP1572962.
JD110467 - Sequence 91491 from Patent EP1572962.
JD203362 - Sequence 184386 from Patent EP1572962.
JD172836 - Sequence 153860 from Patent EP1572962.
JD042302 - Sequence 23326 from Patent EP1572962.
JD553820 - Sequence 534844 from Patent EP1572962.
JD506892 - Sequence 487916 from Patent EP1572962.
JD557227 - Sequence 538251 from Patent EP1572962.
JD492932 - Sequence 473956 from Patent EP1572962.
JD492779 - Sequence 473803 from Patent EP1572962.
JD241417 - Sequence 222441 from Patent EP1572962.
JD226045 - Sequence 207069 from Patent EP1572962.
JD082396 - Sequence 63420 from Patent EP1572962.
JD288192 - Sequence 269216 from Patent EP1572962.
JD515862 - Sequence 496886 from Patent EP1572962.
JD080973 - Sequence 61997 from Patent EP1572962.
JD083645 - Sequence 64669 from Patent EP1572962.
JD370954 - Sequence 351978 from Patent EP1572962.
JD226280 - Sequence 207304 from Patent EP1572962.
JD304488 - Sequence 285512 from Patent EP1572962.
JD431906 - Sequence 412930 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9NZN5 (Reactome details) participates in the following event(s):

R-HSA-398184 LARG activation by G alpha 12/13
R-HSA-398185 LARG binds plexin B1
R-HSA-416594 LARG and PDZ-RhoGEF binds to Plexin-B1
R-HSA-194913 GEFs activate Rho GTPase:GDP
R-HSA-419166 GEFs activate RhoA,B,C
R-HSA-205039 p75NTR indirectly activates RAC and Cdc42 via a guanyl-nucleotide exchange factor
R-HSA-416588 Activation of Rho by LARG and PDZ-RhoGEF
R-HSA-416482 G alpha (12/13) signalling events
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse
R-HSA-388396 GPCR downstream signalling
R-HSA-194840 Rho GTPase cycle
R-HSA-193648 NRAGE signals death through JNK
R-HSA-400685 Sema4D in semaphorin signaling
R-HSA-372790 Signaling by GPCR
R-HSA-194315 Signaling by Rho GTPases
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE
R-HSA-373755 Semaphorin interactions
R-HSA-162582 Signal Transduction
R-HSA-193704 p75 NTR receptor-mediated signalling
R-HSA-422475 Axon guidance
R-HSA-73887 Death Receptor Signalling
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: ARHGC_HUMAN, ENST00000397843.1, ENST00000397843.2, ENST00000397843.3, ENST00000397843.4, ENST00000397843.5, ENST00000397843.6, KIAA0382, LARG, NM_015313, O15086, Q6P526, Q9NZN5, uc318zie.1, uc318zie.2
UCSC ID: ENST00000397843.7_6
RefSeq Accession: NM_015313.3
Protein: Q9NZN5 (aka ARHGC_HUMAN or ARHC_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.