ARHGEF12 (Rho guanine nucleotide exchange factor (GEF) 12)
2000-04-01 Jean-Loup Huret AffiliationGenetics, 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
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
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 ID | Last Year | Title | Authors |
|---|---|---|---|
| 10681437 | 2000 | Identification 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000196914 | ENST00000356641 | Q9NZN5 |
| ENSG00000196914 | ENST00000397843 | Q9NZN5 |
| ENSG00000196914 | ENST00000532993 | E9PMR6 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36520365 | 2023 | Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN degradation, and reduces tumorigenicity. | 1 |
| 36520365 | 2023 | Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN degradation, and reduces tumorigenicity. | 1 |
| 35294066 | 2022 | ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak. | 2 |
| 35294066 | 2022 | ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak. | 2 |
| 31467124 | 2020 | ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients. | 14 |
| 31467124 | 2020 | ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients. | 14 |
| 29279389 | 2018 | RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases. | 20 |
| 29279389 | 2018 | RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases. | 20 |
| 26483157 | 2016 | Mitotic-dependent phosphorylation of leukemia-associated RhoGEF (LARG) by Cdk1. | 6 |
| 27345948 | 2016 | Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation. | 6 |
| 26483157 | 2016 | Mitotic-dependent phosphorylation of leukemia-associated RhoGEF (LARG) by Cdk1. | 6 |
| 27345948 | 2016 | Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation. | 6 |
| 25637523 | 2015 | ARHGEF12 influences the risk of glaucoma by increasing intraocular pressure. | 52 |
| 26627240 | 2015 | Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF. | 8 |
| 25637523 | 2015 | ARHGEF12 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/arhgef12-(rho-guanine-nucleotide-exchange-factor-(gef)-12)
