RABGEF1
protein-codingRAB guanine nucleotide exchange factor 1, the group of VPS9 domain containing
Gene summary
RABGEF1 forms a complex with rabaptin-5 (RABPT5; MIM 603616) that is required for endocytic membrane fusion, and it serves as a specific guanine nucleotide exchange factor (GEF) for RAB5 (RAB5A; MIM 179512) (Horiuchi et al., 1997 [PubMed 9323142]).[supplied by OMIM, Mar 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~129.3 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 RABGEF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014504.3. 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 | 1 | 2 | 3 | |||
| missense | 48 | 1 | 49 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 51 | 3 | 0 | 54 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055319.1 | 8 | MANE Select | |
| Ensembl | ENSP00000284957.4 | 8 | MANE Select | |
| RefSeq | NP_001273989.1 | 5 | Standard | |
| RefSeq | NP_001273990.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rabgef1 | Danio rerio | Structure: pronephric glomerulus Quality: permeability abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of Ras family activation
- Vesicle-mediated transport
- TBC/RABGAPs
- Membrane Trafficking
- Rab regulation of trafficking
Biological Process
- protein targeting to membrane
- endocytosis
Molecular Function
- DNA binding
- protein binding
- zinc ion binding
- Rab guanyl-nucleotide exchange factor activity
- Rab GTPase binding
Cellular Component
- nucleolus
- early endosome
- cytosol
- early endosome membrane
- recycling endosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000284957
- Coding exons
- 8
- Length
- 129301
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125746
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.47 | 210 | 279 | 0.753 | 0.0000158 | 3274 |
| Missense (PolyPhen) | 20 | 64.958 | 0.30789 | 772 | ||
| Synonymous | 0.754 | 91 | 101 | 0.904 | 0.00000596 | 875 |
| Loss of Function | 2.90 | 10 | 25.9 | 0.385 | 0.00000149 | 296 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000072 | 0.000070 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Rab effector protein acting as linker between gamma- adaptin, RAB4A or RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates nucleotide exchange on RAB5A. Can act as a ubiquitin ligase (By similarity). {ECO:0000250, ECO:0000269|PubMed:11452015, ECO:0000269|PubMed:15339665, ECO:0000269|PubMed:9323142}.;
Recessive Scores
- pRec
- 0.0840
Intolerance Scores
- RVIS EVS
- -0.43
- RVIS percentile EVS
- 25.37
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Indispensability pred.
- E
- Indispensability score
- 0.888
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |