RAPGEF1
protein-codingRap guanine nucleotide exchange factor 1
Gene summary
This gene encodes a human guanine nucleotide exchange factor. It transduces signals from CRK by binding the SH3 domain of CRK, and activating several members of the Ras family of GTPases. This signaling cascade that may be involved in apoptosis, integrin-mediated signal transduction, and cell transformation. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]
- GRF2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~163.3 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 RAPGEF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001377935.1. 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 | 2 | 2 | 4 | |||
| missense | 119 | 3 | 122 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 127 | 3 | 2 | 132 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001364864.1 | 27 | MANE Select | |
| Ensembl | ENSP00000508246.1 | 27 | MANE Select | |
| RefSeq | NP_001291204.1 | 24 | Standard | |
| RefSeq | NP_001364865.1 | 24 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Focal adhesion - Homo sapiens (human)
- Renal cell carcinoma - Homo sapiens (human)
- Neurotrophin signaling pathway - Homo sapiens (human)
- Rap1 signaling pathway - Homo sapiens (human)
- Insulin signaling pathway - Homo sapiens (human)
Biological Process
- activation of MAPKK activity
- blood vessel development
- signal transduction
- transmembrane receptor protein tyrosine kinase signaling pathway
- positive regulation of neuron projection development
Molecular Function
- guanyl-nucleotide exchange factor activity
- protein binding
- Rap guanyl-nucleotide exchange factor activity
- SH3 domain binding
Cellular Component
- cytoplasm
- early endosome
- cytosol
- phagocytic vesicle membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000372190
- Coding exons
- 24
- Length
- 163305
- Individuals with no LoFs
- 124642
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 124663
- p
- 0.0000842
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.13 | 431 | 657 | 0.656 | 0.0000401 | 7118 |
| Missense (PolyPhen) | 133 | 272.8 | 0.48754 | 2900 | ||
| Synonymous | 0.822 | 267 | 285 | 0.938 | 0.0000197 | 2179 |
| Loss of Function | 6.28 | 7 | 59.1 | 0.118 | 0.00000320 | 654 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.000093 | 0.000093 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. Transduces signals from CRK to activate RAS. Plays a role in the establishment of basal endothelial barrier function. Plays a role in nerve growth factor (NGF)-induced sustained activation of Rap1 and neurite outgrowth. {ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:7806500}.;
Recessive Scores
- pRec
- 0.199
Intolerance Scores
- RVIS EVS
- -1.77
- RVIS percentile EVS
- 2.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.907
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |