RAPGEF5
protein-codingRap guanine nucleotide exchange factor 5
Gene summary
Members of the RAS (see HRAS; MIM 190020) subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RAPGEF5, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation (Rebhun et al., 2000 [PubMed 10934204]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~238.9 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 RAPGEF5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012294.5. 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 | 1 | 3 | |||
| missense | 1 | 75 | 3 | 79 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 1 | 83 | 4 | 0 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036426.4 | 26 | MANE Select | |
| Ensembl | ENSP00000499535.1 | 26 | MANE Select | |
| RefSeq | NP_001354529.1 | 16 | Standard | |
| RefSeq | NP_001354530.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Rap1 signaling pathway - Homo sapiens (human)
- Ras signaling pathway - Homo sapiens (human)
- Pathways in clear cell renal cell carcinoma
- Ras Signaling
Biological Process
- small GTPase mediated signal transduction
- nervous system development
Molecular Function
- Ras guanyl-nucleotide exchange factor activity
- Rap guanyl-nucleotide exchange factor activity
- GTP-dependent protein binding
Cellular Component
- nucleus
- nucleoplasm
- nuclear body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000344041
- Coding exons
- 23
- Length
- 238908
- Individuals with no LoFs
- 124626
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 124636
- p
- 0.0000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.64 | 276 | 364 | 0.759 | 0.0000186 | 4799 |
| Missense (PolyPhen) | 94 | 144.4 | 0.65096 | 2003 | ||
| Synonymous | 0.224 | 131 | 134 | 0.975 | 0.00000734 | 1266 |
| Loss of Function | 5.30 | 8 | 47.4 | 0.169 | 0.00000251 | 574 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00020 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000068 | 0.000056 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and MRAS/M-Ras-GTP. Its association with MRAS inhibits Rap1 activation. {ECO:0000269|PubMed:10777494, ECO:0000269|PubMed:10934204}.;
Recessive Scores
- pRec
- 0.0809
Intolerance Scores
- LoFtool
- 0.526
- RVIS EVS
- -0.98
- RVIS percentile EVS
- 8.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.788
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |