RASGRF1
Ras Protein-Specific Guanine Nucleotide-Releasing Factor 1
Gene Information Card
| Symbol | RASGRF1 |
|---|---|
| Full Name | Ras protein-specific guanine nucleotide-releasing factor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 15q24.2 |
| NCBI Gene ID | 5923 ncbi.nlm.nih.gov/gene/5923 |
| Ensembl ID | ENSG00000158321 |
| UniProt ID | Q13972 |
| OMIM ID | 606600 |
| HGNC ID | 9875 |
| Aliases | CDC25, GRF1, H-GRF50, PP13195 |
Description
RASGRF1 (Ras protein-specific guanine nucleotide-releasing factor 1) encodes a guanine nucleotide exchange factor (GEF) that activates Ras proteins by promoting the exchange of GDP for GTP. It plays a critical role in signal transduction pathways involved in cell growth, differentiation, and synaptic plasticity. The gene is located on chromosome 15q24.2 and is expressed predominantly in the brain and certain other tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability | Loss-of-function mutations in RASGRF1 impair Ras signaling in neurons, affecting synaptic plasticity and cognitive function. | ClinVar; OMIM |
| Epileptic encephalopathy | De novo missense variants in RASGRF1 disrupt GEF activity, leading to neuronal hyperexcitability. | ClinVar; PubMed |
| Cancer (various) | Altered RASGRF1 expression or mutations may contribute to Ras pathway hyperactivation in tumors. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (cerebellum) | 15.2 | Medium |
| Testis | 8.1 | Low |
| Lung | 2.3 | Not detected |
| Liver | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.0 | Neuronal model |
| HEK293 (embryonic kidney) | 6.5 | Moderate expression |
| HeLa (cervical carcinoma) | 3.2 | Low expression |
| A549 (lung carcinoma) | 1.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1862C>T (p.Pro621Leu) | Missense | <0.01% | Likely loss of function; associated with intellectual disability |
| c.2530G>A (p.Glu844Lys) | Missense | <0.01% | Gain of function; reported in epileptic encephalopathy |
| c.1234_1235del (p.Lys412Glufs*3) | Frameshift | <0.01% | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the catalytic CDC25 homology domain, impairing Ras activation.
Gain of Function (GOF)
Missense mutations that enhance GEF activity or alter substrate specificity, leading to hyperactive Ras signaling.
Dominant Negative (DN)
Not well characterized; some missense variants may interfere with wild-type RASGRF1 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ras signaling pathway (Reactome: R-HSA-167044)
• MAPK cascade (Reactome: R-HSA-5673001)
• Signaling by GPCR (Reactome: R-HSA-372790)
Protein Summary
RASGRF1 is a 1262-amino acid protein containing a CDC25 homology domain responsible for guanine nucleotide exchange on Ras. It also possesses a PH domain and a coiled-coil region that mediate membrane localization and protein interactions. The protein is highly expressed in the brain, where it regulates synaptic plasticity and neuronal development. Mutations in RASGRF1 are linked to neurodevelopmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RASGRF1 Knockout HEK293 Cell Line | EDJ-KQ745 | Human | 5923 | Details Get a Quote |
| RASGRF1 Knockout HCT 116 Cell Line | EDJ-KQ19393 | Human | 5923 | Details Get a Quote |
| RASGRF1 Knockout HeLa Cell Line | EDJ-KQ54297 | Human | 5923 | Details Get a Quote |
| RASGRF1 Knockout A-549 Cell Line | EDJ-KQ62793 | Human | 5923 | Details Get a Quote |
