RAPGEF1
Rap guanine nucleotide exchange factor 1
Basic information
Region (hg38): 9:131576770-131740076
Previous symbols: [ "GRF2" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAPGEF1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 65 | 67 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 1 | |||||
| Total | 0 | 0 | 65 | 2 | 3 |
Variants in RAPGEF1
This is a list of pathogenic ClinVar variants found in the RAPGEF1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 9-131578589-G-A | Benign (Feb 25, 2021) | |||
| 9-131579513-C-T | not specified | Uncertain significance (Mar 22, 2023) | ||
| 9-131579625-C-T | not specified | Uncertain significance (May 08, 2024) | ||
| 9-131582623-G-A | not specified | Uncertain significance (Jan 27, 2022) | ||
| 9-131584333-T-C | not specified | Uncertain significance (Feb 28, 2024) | ||
| 9-131584333-T-G | not specified | Uncertain significance (Mar 01, 2023) | ||
| 9-131584579-A-G | Uncertain significance (Jan 01, 2023) | |||
| 9-131584580-T-C | not specified | Uncertain significance (May 25, 2022) | ||
| 9-131587996-A-C | not specified | Uncertain significance (Aug 05, 2024) | ||
| 9-131588024-G-A | not specified | Uncertain significance (Jun 29, 2022) | ||
| 9-131588026-C-A | not specified | Uncertain significance (Feb 28, 2024) | ||
| 9-131588814-C-G | not specified | Uncertain significance (Dec 10, 2024) | ||
| 9-131588814-C-T | not specified | Uncertain significance (Oct 30, 2024) | ||
| 9-131588921-T-C | not specified | Likely benign (Dec 21, 2022) | ||
| 9-131588921-T-G | not specified | Uncertain significance (Jul 08, 2022) | ||
| 9-131588933-C-T | not specified | Uncertain significance (Apr 08, 2024) | ||
| 9-131589945-G-C | not specified | Uncertain significance (Oct 06, 2024) | ||
| 9-131592125-C-G | not specified | Uncertain significance (May 31, 2023) | ||
| 9-131592175-A-C | not specified | Uncertain significance (Nov 01, 2022) | ||
| 9-131596334-T-C | not specified | Uncertain significance (Oct 01, 2024) | ||
| 9-131596338-C-T | Benign (Jul 30, 2018) | |||
| 9-131596360-G-A | not specified | Uncertain significance (Apr 20, 2024) | ||
| 9-131598270-C-T | not specified | Uncertain significance (Jan 19, 2024) | ||
| 9-131598281-G-A | not specified | Uncertain significance (Nov 18, 2023) | ||
| 9-131598297-G-C | not specified | Uncertain significance (Apr 21, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RAPGEF1 | protein_coding | protein_coding | ENST00000372190 | 24 | 163305 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000461 | 124642 | 0 | 21 | 124663 | 0.0000842 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.13 | 431 | 657 | 0.656 | 0.0000401 | 7118 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000130 | 0.000129 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000556 | 0.0000556 |
| Finnish | 0.0000929 | 0.0000928 |
| European (Non-Finnish) | 0.000142 | 0.000142 |
| Middle Eastern | 0.0000556 | 0.0000556 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
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}.;
- Pathway
- 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);Integrin-mediated Cell Adhesion;Androgen Receptor Network in Prostate Cancer;B Cell Receptor Signaling Pathway;IL-3 Signaling Pathway;Focal Adhesion;Signaling of Hepatocyte Growth Factor Receptor;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;MET in type 1 papillary renal cell carcinoma;Insulin Signaling;Interferon type I signaling pathways;Signal Transduction;Signaling by Interleukins;integrin signaling pathway;Cytokine Signaling in Immune system;GPCR Adenosine A2A receptor;Signaling by PDGF;HGF;TCR;Immune System;MET activates RAP1 and RAC1;BCR;GPCR signaling-G alpha s PKA and ERK;Frs2-mediated activation;Prolonged ERK activation events;Signalling to ERKs;Signaling by NTRK1 (TRKA);Integrin;Signaling by NTRKs;Downstream signal transduction;IFN-gamma pathway;EPO signaling pathway;IL5;MET promotes cell motility;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Insulin Pathway;Nectin adhesion pathway;Neurotrophic factor-mediated Trk receptor signaling;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Signaling events mediated by focal adhesion kinase;Reelin signaling pathway;PDGFR-beta signaling pathway;PDGFR-alpha signaling pathway;E-cadherin signaling in the nascent adherens junction;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling
(Consensus)
Recessive Scores
- pRec
- 0.199
Intolerance Scores
- loftool
- rvis_EVS
- -1.77
- rvis_percentile_EVS
- 2.32
Haploinsufficiency Scores
- pHI
- 0.171
- hipred
- Y
- hipred_score
- 0.775
- ghis
- 0.567
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.907
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rapgef1
- Phenotype
- embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- activation of MAPKK activity;blood vessel development;signal transduction;transmembrane receptor protein tyrosine kinase signaling pathway;positive regulation of neuron projection development;cytokine-mediated signaling pathway;Rap protein signal transduction;nerve growth factor signaling pathway;positive regulation of GTPase activity;regulation of JNK cascade;positive regulation of Ras protein signal transduction;negative regulation of Ras protein signal transduction;platelet-derived growth factor receptor signaling pathway;negative regulation of protein kinase B signaling;establishment of endothelial barrier;negative regulation of ERK1 and ERK2 cascade;positive regulation of ERK1 and ERK2 cascade;cellular response to cAMP;negative regulation of canonical Wnt signaling pathway;activation of GTPase activity;cell-cell adhesion;regulation of cell junction assembly;positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis;cellular response to nerve growth factor stimulus;negative regulation of neural precursor cell proliferation
- Cellular component
- cytoplasm;early endosome;cytosol;phagocytic vesicle membrane;protein-containing complex;perinuclear region of cytoplasm
- Molecular function
- guanyl-nucleotide exchange factor activity;protein binding;Rap guanyl-nucleotide exchange factor activity;SH3 domain binding