RASGRP1 (RAS Guanyl Releasing Protein 1) is a protein-coding gene located on chromosome 15q14. Alternatively spliced transcript variants encoding different isoforms have been identified.
RASGRP1 Gene
DefinitionThis section has been translated automatically.
General informationThis section has been translated automatically.
The RASGRP1 gene belongs to a family of genes characterized by the presence of a guanine nucleotide exchange factor (GEF) domain of the Ras superfamily. It functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor that specifically activates Ras by exchanging bound GDP for GTP. It activates the Erk/MAP kinase cascade and regulates T cell and B cell development, homeostasis, and differentiation.
Altered expression of the various isoforms of this protein may be a cause of susceptibility to systemic lupus erythematosus (SLE).
PathophysiologyThis section has been translated automatically.
The encoded protein functions as a calcium and diacylglycerol (DAG)-regulated nucleotide exchange factor that specifically activates Ras by exchanging bound GDP for GTP (Roose JP et al. 2005). Activates the Erk/MAP kinase cascade. Regulates T lymphocyte/B lymphocyte development, homeostasis, and differentiation by coupling T lymphocyte/B lymphocyte antigen receptors to Ras (Ebinu JO et al 2000). Regulates NK cell cytotoxicity and ITAM-dependent cytokine production through activation of Ras-mediated ERK and JNK pathways. Acts in mast cell degranulation and cytokine secretion and regulates FcERI-triggered allergic responses. May also play a role in the differentiation of other cell types (Bivona TG et al. 2003).
Clinical pictureThis section has been translated automatically.
Diseases associated with RASGRP1 include:
- immunodeficiency 64
- and
- Autoimmune lymphoproliferative syndrome.
LiteratureThis section has been translated automatically.
- Bivona TG et al. (2003) Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Nature 424(6949):694-698.
- Ebinu JO et al (2000) RasGRP links T-cell receptor signaling to Ras. Blood 95:3199-3203.
- Mao H et al (2018) RASGRP1 mutation in autoimmune lymphoproliferative syndrome-like disease. J. Allergy Clin. Immun. 142: 595-604.
- Platt CD et al. (2017) Combined immunodeficiency with EBV positive B cell lymphoma and epidermodysplasia verruciformis due to a novel homozygous mutation in RASGRP1. (Letter) Clin Immun 183: 142-144.
- Roose JP et al (2005) A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells. Mol Cell Biol 25:4426-4441