PREX1
protein-codingphosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1, the group of Dbl family Rho GEFs|PDZ domain containing|Pleckstrin homology domain containing
Gene summary
The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs). It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. The encoded protein, which is found mainly in the cytoplasm, is activated by phosphatidylinositol-3,4,5-trisphosphate and the beta-gamma subunits of heterotrimeric G proteins. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~203.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PREX1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020820.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 8 | 5 | 16 | ||
| missense | 199 | 10 | 209 | |||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 209 | 18 | 5 | 232 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065871.3 | 40 | MANE Select | |
| Ensembl | ENSP00000361009.3 | 40 | MANE Select | |
| Ensembl | ENSP00000434632.1 | 18 | Standard | |
| Ensembl | ENSP00000481444.1 | 1 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| prex1 | Danio rerio | Structure: GTPase activity Quality: decreased process quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Chemokine signaling pathway - Homo sapiens (human)
- Chemokine signaling pathway
- Signaling by GPCR
- Signal Transduction
Biological Process
- superoxide metabolic process
- G protein-coupled receptor signaling pathway
- actin filament polymerization
- T cell differentiation
- positive regulation of cell migration
Molecular Function
- guanyl-nucleotide exchange factor activity
- Rho guanyl-nucleotide exchange factor activity
- GTPase activator activity
- protein binding
- phospholipid binding
Cellular Component
- cytosol
- plasma membrane
- growth cone
- dendritic shaft
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371941
- Coding exons
- 40
- Length
- 203631
- Individuals with no LoFs
- 125744
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125748
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.69 | 669 | 997 | 0.671 | 0.0000632 | 10897 |
| Missense (PolyPhen) | 162 | 342.73 | 0.47268 | 3652 | ||
| Synonymous | 1.19 | 390 | 421 | 0.926 | 0.0000285 | 3184 |
| Loss of Function | 8.26 | 3 | 85.3 | 0.0352 | 0.00000407 | 1006 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000068 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. May function downstream of heterotrimeric G proteins in neutrophils.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.0897
- RVIS EVS
- 0.07
- RVIS percentile EVS
- 58.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.888
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | Medium |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |