Alt. symbols: P115-RHOGEF | SUB1.5 | LBCL2

Approved name: Rho guanine nucleotide exchange factor 1
Alt. names: Rho guanine nucleotide exchange factor (GEF) 1

Location: 19q13.2: 41883173 - 41930150 (+)
Gene type: protein_coding, 27 transcripts.

Scores: LoFtool: 0.217000 | pLI: 0.90949746 | LOEUF: 0.342

HGNC: 681

NCBI: 9138, RefSeq: .0

Ensembl: ENSG00000076928.20

LRG_ | Status: none

OMIM: 601855

Expression | ProteinAtlas

ARHGEF1 encodes a protein predominantly expressed in hematopoietic cells and specific for regulation of the GTPase RhoA, which plays a role in cytoskeletal signaling and PI3K/AKT pathway control. ARHGEF1 is involved in the signaling of GPCRs associated with G-alpha 12/13-containing heterotrimeric G proteins AKA guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits (PMID: 9641915, 9641916). It acts as a GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange factor (GEF) for RhoA GTPase (PMID: 30521495, 8810315, 9641915, 9641916), an activity inhibited by binding to activated GNA12 (PMID: 9641916). It has been reported to mediate angiotensin-2-induced RhoA activation (PMID: 20098430).

Bouafia et al. (2019) reported compound heterozygous ARHGEF1 mutations (c.898 C>T; p.R300*/c.1669-1G>T) in 2 siblings with low IgG levels and impaired vaccine responses, as well as clinical features of recurrent viral and severe sinopulmonary infections and bronchiectasis (PMID: 30521495). One of the sisters also showed low IgM levels, autoimmune cytopenia, and low isohemagglutinin titers. Both had low absolute B cell counts, as well as reduced MZ, memory and switched memory B cell proportions w ith relatively increased transitional B cells, T cell subset abnormalities and circulating immature myeloid cells (a feature not observed in ARHGEF1 LOF mouse models). Patient T and B cells showed low RhoA activity and low cortical F-actin polymerization, leading to impaired regulation of AKT/mTOR signaling and impaired lymphocyte migration with consequently disrupted B cell distribution within GCs. [Load More]