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
ARHGEF12
LOCATION
11q23.3
LOCUSID
23365
ALIAS
LARG,PRO2792
FUSION GENES
Show Gene Fusions

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

Article 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
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

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
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
365203652023Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN degradation, and reduces tumorigenicity.1
365203652023Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN degradation, and reduces tumorigenicity.1
352940662022ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak.2
352940662022ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak.2
314671242020ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.14
314671242020ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.14
292793892018RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases.20
292793892018RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases.20
264831572016Mitotic-dependent phosphorylation of leukemia-associated RhoGEF (LARG) by Cdk1.6
273459482016Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation.6
264831572016Mitotic-dependent phosphorylation of leukemia-associated RhoGEF (LARG) by Cdk1.6
273459482016Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation.6
256375232015ARHGEF12 influences the risk of glaucoma by increasing intraocular pressure.52
266272402015Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF.8
256375232015ARHGEF12 influences the risk of glaucoma by increasing intraocular pressure.52

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/meetings/gene-fusions-explorer/js/web-card-gene.js