ARHGEF12 (Rho guanine nucleotide exchange factor (GEF) 12)

2000-04-01   Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC
LOCATION
11q23.3
LOCUSID
ALIAS
LARG,PRO2792
FUSION GENES

DNA/RNA

Transcription

9501 bp mRNA; 4634 bp open reading frame

Proteins

Atlas Image

Description

the gene encodes a guanine nucleotide exchange factor; 1544 amino acids; NH2- PDZ domain, Lsc homology (LH) domain, bipartite nuclear localization signal, Dbl homology (DH) domain, and a pleckstrin homology (PH) domain -COOH

Expression

wide (leukocytes, spleen, prostate, testis, ovary, small intestine, colon, thymus)

Function

PDZ domains are involved in protein-protein interactions in transmembrane signaling pathways; LH domains bind G proteins; nuclear localization signals are implicated in translocation of proteins from the cytoplasm to the nucleus; DH domains are responsible for the nucleotide exchange activity of guanine nucleotide exchange (GEF) toward Rho GTPases, PH domains function in membrane localization; Rho GEF are regulators of GTPases, and have oncogenic properties

Homology

member of the family of Rho GEF factors, like dbl, vav, tiam, and BCR

Implicated in

Entity name
acute non lymphocytic leukemia (AML) with apparently normal cromosomes 11 --> KMT2A- LARG
Note
poorly defined: only 1 case to date, a 38 yr old male patient with occupational exposure; M4-AML; CR; death unrelated to the leukemia
Cytogenetics
the case was 51,XY,+8,+19,+3mar; the interstitial deletion at 11q23 resulting in MLL-LARG fusion cannot be seen at the chromosome level
Hybrid gene
5 MLL fused at exon 6 with the 3 end of almost the entire LARG; LARG is oriented in a 5 to 3direction, like MLL
Fusion protein
excludes the NH2- PDZ domain of LARG, and includes most of LARG, from the Lsc homology (LH) domain to COOH

Bibliography

Pubmed IDLast YearTitleAuthors
106814372000Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with MLL in acute myeloid leukemia.Kourlas PJ et al

Other Information

Locus ID:

NCBI: 23365
MIM: 604763
HGNC: 14193
Ensembl: ENSG00000196914

Variants:

dbSNP: 23365
ClinVar: 23365
TCGA: ENSG00000196914
COSMIC: ARHGEF12

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000196914ENST00000356641Q9NZN5
ENSG00000196914ENST00000397843Q9NZN5
ENSG00000196914ENST00000532993E9PMR6

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
Axon guidanceKEGGko04360
Regulation of actin cytoskeletonKEGGko04810
Axon guidanceKEGGhsa04360
Regulation of actin cytoskeletonKEGGhsa04810
Pathways in cancerKEGGhsa05200
Vascular smooth muscle contractionKEGGhsa04270
Vascular smooth muscle contractionKEGGko04270
TuberculosisKEGGko05152
TuberculosisKEGGhsa05152
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Platelet activationKEGGhsa04611
Signal TransductionREACTOMER-HSA-162582
Signalling by NGFREACTOMER-HSA-166520
p75 NTR receptor-mediated signallingREACTOMER-HSA-193704
Cell death signalling via NRAGE, NRIF and NADEREACTOMER-HSA-204998
NRAGE signals death through JNKREACTOMER-HSA-193648
Signaling by Rho GTPasesREACTOMER-HSA-194315
Rho GTPase cycleREACTOMER-HSA-194840
Signaling by GPCRREACTOMER-HSA-372790
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (12/13) signalling eventsREACTOMER-HSA-416482
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
Semaphorin interactionsREACTOMER-HSA-373755
Sema4D in semaphorin signalingREACTOMER-HSA-400685
Sema4D induced cell migration and growth-cone collapseREACTOMER-HSA-416572

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
165650892006Hyaluronan-CD44 interaction with leukemia-associated RhoGEF and epidermal growth factor receptor promotes Rho/Ras co-activation, phospholipase C epsilon-Ca2+ signaling, and cytoskeleton modification in head and neck squamous cell carcinoma cells.85
121834582002Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF.79
125158662003Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF.69
153315922004Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor.65
121966282002The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG.63
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
117991112002Regulation of G protein-linked guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and LARG by tyrosine phosphorylation: evidence of a role for focal adhesion kinase.52
192736162009Unc5B associates with LARG to mediate the action of repulsive guidance molecule.43
214544922011Mechanistic insights into specificity, activity, and regulatory elements of the regulator of G-protein signaling (RGS)-containing Rho-specific guanine nucleotide exchange factors (GEFs) p115, PDZ-RhoGEF (PRG), and leukemia-associated RhoGEF (LARG).31
256375232015ARHGEF12 influences the risk of glaucoma by increasing intraocular pressure.30

Citation

Jean-Loup Huret

ARHGEF12 (Rho guanine nucleotide exchange factor (GEF) 12)

Atlas Genet Cytogenet Oncol Haematol. 2000-04-01

Online version: http://atlasgeneticsoncology.org/gene/243/arhgef12-(rho-guanine-nucleotide-exchange-factor-(gef)-12)