PREX1 Gene (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 1)
Key regulator of Rac signaling in immune cells and cancer
Gene Information Card
| Symbol | PREX1 |
|---|---|
| Full Name | Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q13.13 |
| NCBI Gene ID | 57580 ncbi.nlm.nih.gov/gene/57580 |
| Ensembl ID | ENSG00000124126 |
| UniProt ID | Q8TCU6 |
| OMIM ID | 605859 |
| HGNC ID | 16894 |
| Aliases | P-REX1, MGC133230 |
Description
PREX1 encodes a guanine nucleotide exchange factor (GEF) that specifically activates Rac small GTPases. It is synergistically activated by phosphatidylinositol-3,4,5-trisphosphate (PIP3) and Gβγ subunits, linking PI3K and G protein-coupled receptor (GPCR) signaling to Rac-mediated cytoskeletal reorganization, cell migration, and reactive oxygen species production.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | PREX1 overexpression promotes Rac1 activation and metastatic invasion | PMID: 19151757; COSMIC |
| Prostate cancer | PREX1 amplification and overexpression correlate with Rac1 hyperactivation and poor prognosis | PMID: 23093971; COSMIC |
| Immunodeficiency (familial) | Homozygous loss-of-function mutations impair neutrophil chemotaxis and respiratory burst | PMID: 27869123; ClinVar |
| Melanoma | PREX1 upregulation drives Rac-dependent cell motility and invasion | PMID: 22492985; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Lymph node | 8.3 | Medium |
| Spleen | 7.1 | Medium |
| Whole blood | 5.2 | Low |
| Brain | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| MCF7 | 9.8 | Medium expression |
| PC3 | 11.4 | High expression |
| Jurkat | 6.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Glu49Lys | Missense | 0.2% (COSMIC) | Reduced GEF activity |
| p.Arg510* | Nonsense | <0.1% (ClinVar) | Loss of function |
| p.Pro848Leu | Missense | 0.3% (COSMIC) | Unknown |
| Amplification | Copy number gain | 5-10% (breast cancer) | Increased expression |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg510*) lead to truncated protein lacking catalytic DH-PH domain, impairing Rac activation.
Gain of Function (GOF)
Amplification and overexpression in cancers increase Rac1-GTP levels, promoting cell migration and invasion.
Dominant Negative (DN)
Not well characterized; some missense variants may sequester PIP3 or Gβγ without activating Rac.
View complete mutation data：
Gene Ontology (GO)
Pathways
• PI3K-Akt signaling pathway (Reactome R-HSA-1257604)
• Rac1 GTPase cycle (Reactome R-HSA-9012999)
• GPCR downstream signaling (Reactome R-HSA-388396)
Protein Summary
PREX1 is a 1659-amino acid protein containing a Dbl homology (DH) domain, a pleckstrin homology (PH) domain, and two DEP domains. It acts as a Rac-specific GEF that is activated by PIP3 and Gβγ. PREX1 is highly expressed in hematopoietic cells and plays critical roles in neutrophil chemotaxis, superoxide production, and cancer cell metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PREX1 Knockout HEK293 Cell Line | EDJ-KQ14150 | Human | 57580 | Details Get a Quote |
| PREX1 Knockout A-549 Cell Line | EDJ-KQ45340 | Human | 57580 | Details Get a Quote |
| PREX1 Knockout HCT 116 Cell Line | EDJ-KQ45342 | Human | 57580 | Details Get a Quote |
| PREX1 Knockout HeLa Cell Line | EDJ-KQ45343 | Human | 57580 | Details Get a Quote |
