RASGRF1
protein-codingRas protein specific guanine nucleotide releasing factor 1, the group of Pleckstrin homology domain containing|Dbl family Rho GEFs
Gene summary
The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) similar to the Saccharomyces cerevisiae CDC25 gene product. Functional analysis has demonstrated that this protein stimulates the dissociation of GDP from RAS protein. The studies of the similar gene in mouse suggested that the Ras-GEF activity of this protein in brain can be activated by Ca2+ influx, muscarinic receptors, and G protein beta-gamma subunit. Mouse studies also indicated that the Ras-GEF signaling pathway mediated by this protein may be important for long-term memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Mar 2009]
- GRF1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~130.9 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 RASGRF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001145648.3. 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 | 12 | 8 | 20 | |||
| missense | 131 | 4 | 1 | 136 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 137 | 16 | 9 | 162 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001139120.1 | 27 | MANE Select | |
| Ensembl | ENSP00000452781.2 | 27 | MANE Select | |
| RefSeq | NP_002882.3 | 28 | Standard | |
| RefSeq | NP_722522.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Focal adhesion - Homo sapiens (human)
- Ras signaling pathway - Homo sapiens (human)
- MAPK signaling pathway - Homo sapiens (human)
- TFs Regulate miRNAs related to cardiac hypertrophy
- Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
Biological Process
- MAPK cascade
- signal transduction
- small GTPase mediated signal transduction
- long-term memory
- cell population proliferation
Molecular Function
- guanyl-nucleotide exchange factor activity
- Ras guanyl-nucleotide exchange factor activity
- Rho guanyl-nucleotide exchange factor activity
- glutamate receptor binding
Cellular Component
- cytosol
- plasma membrane
- growth cone
- neuron projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000419573
- Coding exons
- 28
- Length
- 130827
- Individuals with no LoFs
- 125678
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 70
- Defined
- 125748
- p
- 0.000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.21 | 446 | 776 | 0.575 | 0.0000482 | 8406 |
| Missense (PolyPhen) | 111 | 259.31 | 0.42807 | 2671 | ||
| Synonymous | 0.823 | 312 | 331 | 0.942 | 0.0000223 | 2437 |
| Loss of Function | 6.58 | 7 | 63.6 | 0.110 | 0.00000307 | 743 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00045 | 0.00044 | rare |
| South Asian | 0.000037 | 0.000033 | rare |
| Other | 0.00098 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Promotes the exchange of Ras-bound GDP by GTP. {ECO:0000269|PubMed:11389730}.;
Recessive Scores
- pRec
- 0.167
Intolerance Scores
- LoFtool
- 0.170
- RVIS EVS
- -1.41
- RVIS percentile EVS
- 4.14
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.746
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |