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 sur... See more...

Aliases for RAPGEF5 Gene

Aliases for RAPGEF5 Gene

  • Rap Guanine Nucleotide Exchange Factor 5 2 3 3 4 5
  • Rap Guanine Nucleotide Exchange Factor (GEF) 5 2 3
  • Guanine Nucleotide Exchange Factor For Rap1 3 4
  • M-Ras-Regulated Rap GEF 3 4
  • M-Ras-Regulated GEF 2 3
  • Related To Epac 3 4
  • MR-GEF 3 4
  • GFR 3 4
  • KIAA0277 4
  • REPAC 3
  • MRGEF 4
  • Repac 4

External Ids for RAPGEF5 Gene

Previous GeneCards Identifiers for RAPGEF5 Gene

  • GC07M021903
  • GC07M021931

Summaries for RAPGEF5 Gene

Entrez Gene Summary for RAPGEF5 Gene

  • 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]

GeneCards Summary for RAPGEF5 Gene

RAPGEF5 (Rap Guanine Nucleotide Exchange Factor 5) is a Protein Coding gene. Among its related pathways are Ras signaling pathway and G-protein signaling_Cross-talk between Ras-family GTPases. Gene Ontology (GO) annotations related to this gene include guanyl-nucleotide exchange factor activity and Ras guanyl-nucleotide exchange factor activity. An important paralog of this gene is RAPGEF4.

UniProtKB/Swiss-Prot Summary for RAPGEF5 Gene

  • Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and MRAS/M-Ras-GTP. Its association with MRAS inhibits Rap1 activation.

Gene Wiki entry for RAPGEF5 Gene

Additional gene information for RAPGEF5 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RAPGEF5 Gene

Genomics for RAPGEF5 Gene

GeneHancer (GH) Regulatory Elements for RAPGEF5 Gene

Promoters and enhancers for RAPGEF5 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH07J022355 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 512.2 -0.6 -603 5.1 EP300 FOXK2 POLR2G NCOR1 CTCF ZIC2 POLR2A KDM6A TCF7 FOXA1 RAPGEF5 lnc-STEAP1B-4 lnc-STEAP1B-5 piR-33804-080
GH07J022498 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 500.1 -142.6 -142580 2.1 CTCF REST TOE1 CTBP1 MYC NFRKB TAF9B MXI1 POLR2A KDM5B STEAP1B lnc-RAPGEF5-1 RAPGEF5 piR-32214-615
GH07J022191 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 505.6 +163.9 163866 2.2 EP300 TEAD4 HDAC2 SMC3 MXI1 YY1 POLR2A TCF12 RBM22 SIN3A RAPGEF5 lnc-STEAP1B-6 LOC102724143
GH07J022301 Enhancer 0.9 ENCODE dbSUPER 17.5 +55.0 54981 0.6 HES1 MYC HDAC3 NCOR1 POLR2A IRF1 ZNF592 POLR2H TAL1 ZNF395 RAPGEF5 RNA5SP227 lnc-STEAP1B-5
GH07J022429 Enhancer 1.4 Ensembl ENCODE dbSUPER 11.8 -75.5 -75458 6.8 ZNF217 NCOR1 KDM6A ZBTB11 TCF7 ZNF623 AFF1 TARDBP HES1 ZBTB25 RAPGEF5 NUP42 AK3P3 RPL12P10 piR-43164-061 lnc-IL6-4 STEAP1B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RAPGEF5 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RAPGEF5

Top Transcription factor binding sites by QIAGEN in the RAPGEF5 gene promoter:
  • AP-1
  • AP-4
  • C/EBPalpha
  • CP2
  • MyoD
  • MZF-1
  • NF-1
  • NF-1/L
  • p53
  • S8

Genomic Locations for RAPGEF5 Gene

Genomic Locations for RAPGEF5 Gene
chr7:22,118,236-22,357,154
(GRCh38/hg38)
Size:
238,919 bases
Orientation:
Minus strand
chr7:22,157,856-22,396,763
(GRCh37/hg19)
Size:
238,908 bases
Orientation:
Minus strand

Genomic View for RAPGEF5 Gene

Genes around RAPGEF5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RAPGEF5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RAPGEF5 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RAPGEF5 Gene

Proteins for RAPGEF5 Gene

  • Protein details for RAPGEF5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q92565-RPGF5_HUMAN
    Recommended name:
    Rap guanine nucleotide exchange factor 5
    Protein Accession:
    Q92565
    Secondary Accessions:
    • A4D140
    • Q8IXU5

    Protein attributes for RAPGEF5 Gene

    Size:
    580 amino acids
    Molecular mass:
    67733 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=BAA13406.2; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RAPGEF5 Gene

    Alternative splice isoforms for RAPGEF5 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RAPGEF5 Gene

Post-translational modifications for RAPGEF5 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for RAPGEF5 Gene

Domains & Families for RAPGEF5 Gene

Gene Families for RAPGEF5 Gene

Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for RAPGEF5 Gene

Suggested Antigen Peptide Sequences for RAPGEF5 Gene

GenScript: Design optimal peptide antigens:
  • Related to Epac (RPGF5_HUMAN)
genes like me logo Genes that share domains with RAPGEF5: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for RAPGEF5 Gene

Function for RAPGEF5 Gene

Molecular function for RAPGEF5 Gene

UniProtKB/Swiss-Prot Function:
Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and MRAS/M-Ras-GTP. Its association with MRAS inhibits Rap1 activation.

Phenotypes From GWAS Catalog for RAPGEF5 Gene

Gene Ontology (GO) - Molecular Function for RAPGEF5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005088 Ras guanyl-nucleotide exchange factor activity TAS 10934204
GO:0017034 Rap guanyl-nucleotide exchange factor activity IDA 10486569
GO:0030742 GTP-dependent protein binding IPI 10934204
genes like me logo Genes that share ontologies with RAPGEF5: view
genes like me logo Genes that share phenotypes with RAPGEF5: view

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for RAPGEF5 Gene

Localization for RAPGEF5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RAPGEF5 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RAPGEF5 gene
Compartment Confidence
nucleus 5
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RAPGEF5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005634 nucleus IDA,IEA 10486569
GO:0005654 nucleoplasm IDA --
GO:0016604 nuclear body IDA --
genes like me logo Genes that share ontologies with RAPGEF5: view

Pathways & Interactions for RAPGEF5 Gene

PathCards logo

SuperPathways for RAPGEF5 Gene

SuperPathway Contained pathways
1 Ras signaling pathway
2 Development Angiotensin activation of ERK
.65
3 G-protein signaling Regulation of p38 and JNK signaling mediated by G-proteins
.40
4 G-protein signaling_Cross-talk between Ras-family GTPases
-
5 G-protein signaling_Rap1A regulation pathway
-
genes like me logo Genes that share pathways with RAPGEF5: view

Pathways by source for RAPGEF5 Gene

2 KEGG pathways for RAPGEF5 Gene
5 GeneGo (Thomson Reuters) pathways for RAPGEF5 Gene
  • Development G-Proteins mediated regulation MARK-ERK signaling
  • G-protein signaling G-Protein alpha-12 signaling pathway
  • G-protein signaling_Cross-talk between Ras-family GTPases
  • G-protein signaling_Rap1A regulation pathway
  • G-protein signaling_Rap2B regulation pathway

SIGNOR curated interactions for RAPGEF5 Gene

Activates:

Gene Ontology (GO) - Biological Process for RAPGEF5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007264 small GTPase mediated signal transduction NAS 10486569
GO:0007399 nervous system development NAS 10486569
GO:0035556 intracellular signal transduction IEA --
genes like me logo Genes that share ontologies with RAPGEF5: view

Drugs & Compounds for RAPGEF5 Gene

(4) Drugs for RAPGEF5 Gene - From: PharmGKB and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Guanosine diphosphate Experimental Pharma 0
Guanosine monophosphate Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0
antidepressants Pharma 0
genes like me logo Genes that share compounds with RAPGEF5: view

Transcripts for RAPGEF5 Gene

mRNA/cDNA for RAPGEF5 Gene

5 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for RAPGEF5 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c · 3d ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14a · 14b · 14c ^ 15a · 15b ^ 16 ^ 17a · 17b ^ 18 ^
SP1: - - - -
SP2: - - - - - - - -
SP3:
SP4: - - - - -
SP5:
SP6: -
SP7:

ExUns: 19 ^ 20 ^ 21
SP1: -
SP2: -
SP3:
SP4:
SP5:
SP6:
SP7:

Relevant External Links for RAPGEF5 Gene

GeneLoc Exon Structure for
RAPGEF5

Expression for RAPGEF5 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RAPGEF5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RAPGEF5 Gene

This gene is overexpressed in Brain - Spinal cord (cervical c-1) (x9.2) and Brain - Substantia nigra (x4.5).

Protein differential expression in normal tissues from HIPED for RAPGEF5 Gene

This gene is overexpressed in Adipocyte (20.1), Liver (19.0), Spleen (13.6), and Neutrophil (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RAPGEF5 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RAPGEF5

SOURCE GeneReport for Unigene cluster for RAPGEF5 Gene:

Hs.174768

mRNA Expression by UniProt/SwissProt for RAPGEF5 Gene:

Q92565-RPGF5_HUMAN
Tissue specificity: Widely expressed with highest levels in brain.

Evidence on tissue expression from TISSUES for RAPGEF5 Gene

  • Nervous system(4.8)
genes like me logo Genes that share expression patterns with RAPGEF5: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for RAPGEF5 Gene

Orthologs for RAPGEF5 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for RAPGEF5 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RAPGEF5 31 30
  • 99.68 (n)
OneToOne
dog
(Canis familiaris)
Mammalia RAPGEF5 31 30
  • 92.42 (n)
OneToOne
cow
(Bos Taurus)
Mammalia RAPGEF5 31 30
  • 90.32 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Rapgef5 17 31 30
  • 88.22 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia RAPGEF5 31
  • 84 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia RAPGEF5 31
  • 79 (a)
OneToOne
chicken
(Gallus gallus)
Aves RAPGEF5 31 30
  • 77.87 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RAPGEF5 31
  • 71 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rapgef5 30
  • 75.14 (n)
zebrafish
(Danio rerio)
Actinopterygii rapgef5a 31 30
  • 62.73 (n)
OneToMany
rapgef5b 31
  • 46 (a)
OneToMany
wufk78a01 30
fruit fly
(Drosophila melanogaster)
Insecta Epac 31
  • 25 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea epac-1 31
  • 21 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes BUD5 33
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 27 (a)
OneToMany
Species where no ortholog for RAPGEF5 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for RAPGEF5 Gene

ENSEMBL:
Gene Tree for RAPGEF5 (if available)
TreeFam:
Gene Tree for RAPGEF5 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RAPGEF5: view image

Paralogs for RAPGEF5 Gene

(6) SIMAP similar genes for RAPGEF5 Gene using alignment to 6 proteins:

  • RPGF5_HUMAN
  • A8MQ07_HUMAN
  • C9JBS6_HUMAN
  • C9JHM4_HUMAN
  • E9PGY3_HUMAN
  • F8WD32_HUMAN
genes like me logo Genes that share paralogs with RAPGEF5: view

Variants for RAPGEF5 Gene

Additional dbSNP identifiers (rs#s) for RAPGEF5 Gene

Structural Variations from Database of Genomic Variants (DGV) for RAPGEF5 Gene

Variant ID Type Subtype PubMed ID
esv1239094 CNV deletion 17803354
esv2333221 CNV deletion 18987734
esv2661030 CNV deletion 23128226
esv2665146 CNV deletion 23128226
esv2734118 CNV deletion 23290073
esv2734119 CNV deletion 23290073
esv2734120 CNV deletion 23290073
esv3612511 CNV loss 21293372
esv3612512 CNV loss 21293372
esv3612514 CNV loss 21293372
esv3612515 CNV loss 21293372
esv3612516 CNV loss 21293372
esv4118 CNV loss 18987735
nsv1119109 CNV deletion 24896259
nsv1140750 CNV deletion 24896259
nsv1150347 CNV deletion 26484159
nsv365300 CNV deletion 16902084
nsv606405 CNV loss 21841781
nsv7393 OTHER inversion 18451855
nsv830923 CNV gain 17160897
nsv958423 CNV deletion 24416366

Variation tolerance for RAPGEF5 Gene

Residual Variation Intolerance Score: 56.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.86; 58.90% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RAPGEF5 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
RAPGEF5

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RAPGEF5 Gene

Disorders for RAPGEF5 Gene

Additional Disease Information for RAPGEF5

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for RAPGEF5 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for RAPGEF5 Gene

Publications for RAPGEF5 Gene

  1. Characterization of GFR, a novel guanine nucleotide exchange factor for Rap1. (PMID: 10486569) Ichiba T … Kuraishi Y (FEBS letters 1999) 2 3 4 23 54
  2. Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. (PMID: 10934204) Rebhun JF … Quilliam LA (The Journal of biological chemistry 2000) 3 4 23 54
  3. Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. (PMID: 9039502) Nagase T … Nomura N (DNA research : an international journal for rapid publication of reports on genes and genomes 1996) 2 3 4 54
  4. Genome-wide association scan for survival on dialysis in African-Americans with type 2 diabetes. (PMID: 21546767) Murea M … Freedman BI (American journal of nephrology 2011) 3 41 54
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54

Products for RAPGEF5 Gene

Sources for RAPGEF5 Gene