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 be... See more...

Aliases for RAPGEF1 Gene

Aliases for RAPGEF1 Gene

  • Rap Guanine Nucleotide Exchange Factor 1 2 3 3 4 5
  • Guanine Nucleotide-Releasing Factor 2 (Specific For Crk Proto-Oncogene) 2 3
  • Rap Guanine Nucleotide Exchange Factor (GEF) 1 2 3
  • CRK SH3-Binding GNRP 3 4
  • GRF2 3 4
  • C3G 2 3
  • Guanine Nucleotide-Releasing Factor 2 4
  • Protein C3G 4
  • RAPGEF1 5

External Ids for RAPGEF1 Gene

Previous HGNC Symbols for RAPGEF1 Gene

  • GRF2

Previous GeneCards Identifiers for RAPGEF1 Gene

  • GC09M129729
  • GC09M131481
  • GC09M133441
  • GC09M134452
  • GC09M103946

Summaries for RAPGEF1 Gene

Entrez Gene Summary for RAPGEF1 Gene

  • 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]

GeneCards Summary for RAPGEF1 Gene

RAPGEF1 (Rap Guanine Nucleotide Exchange Factor 1) is a Protein Coding gene. Diseases associated with RAPGEF1 include Hemolytic Uremic Syndrome, Atypical 1 and Transient Refractive Change. Among its related pathways are Signaling by GPCR and Development HGF signaling pathway. Gene Ontology (GO) annotations related to this gene include SH3 domain binding and Rap guanyl-nucleotide exchange factor activity. An important paralog of this gene is ENSG00000273217.

UniProtKB/Swiss-Prot Summary for RAPGEF1 Gene

  • Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. Transduces signals from CRK to activate RAS. Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1 (PubMed:12432078). 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.

Gene Wiki entry for RAPGEF1 Gene

Additional gene information for RAPGEF1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RAPGEF1 Gene

Genomics for RAPGEF1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RAPGEF1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RAPGEF1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RAPGEF1

Top Transcription factor binding sites by QIAGEN in the RAPGEF1 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • NF-kappaB1

Genomic Locations for RAPGEF1 Gene

Genomic Locations for RAPGEF1 Gene
chr9:131,576,770-131,740,076
(GRCh38/hg38)
Size:
163,307 bases
Orientation:
Minus strand
chr9:134,452,157-134,615,461
(GRCh37/hg19)
Size:
163,305 bases
Orientation:
Minus strand

Genomic View for RAPGEF1 Gene

Genes around RAPGEF1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RAPGEF1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RAPGEF1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RAPGEF1 Gene

Proteins for RAPGEF1 Gene

  • Protein details for RAPGEF1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13905-RPGF1_HUMAN
    Recommended name:
    Rap guanine nucleotide exchange factor 1
    Protein Accession:
    Q13905
    Secondary Accessions:
    • Q5JUE4
    • Q68DL3
    • Q8IV73

    Protein attributes for RAPGEF1 Gene

    Size:
    1077 amino acids
    Molecular mass:
    120548 Da
    Quaternary structure:
    • Interacts with HCK (via SH3-binding sites) (PubMed:14551197). Interacts with CRK (via SH3-binding sites) (PubMed:8662907).

    Three dimensional structures from OCA and Proteopedia for RAPGEF1 Gene

    Alternative splice isoforms for RAPGEF1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RAPGEF1 Gene

Post-translational modifications for RAPGEF1 Gene

  • Phosphorylation at Tyr-504 enhances activity as Rap guanine nucleotide exchange factor.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for RAPGEF1 Gene

Domains & Families for RAPGEF1 Gene

Gene Families for RAPGEF1 Gene

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

Protein Domains for RAPGEF1 Gene

InterPro:
Blocks:
  • Guanine-nucleotide dissociation stimulator CDC25
ProtoNet:

Suggested Antigen Peptide Sequences for RAPGEF1 Gene

GenScript: Design optimal peptide antigens:
  • Guanine nucleotide-releasing factor 2 (A5XEI4_HUMAN)
  • Guanine nucleotide-releasing factor 2 (A5XEI5_HUMAN)
  • Guanine nucleotide-releasing factor 2 (A5XEI6_HUMAN)
  • Guanine nucleotide-releasing factor 2 (A5XEI7_HUMAN)
  • Guanine nucleotide-releasing factor 2 (A5XEI8_HUMAN)
genes like me logo Genes that share domains with RAPGEF1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for RAPGEF1 Gene

Function for RAPGEF1 Gene

Molecular function for RAPGEF1 Gene

UniProtKB/Swiss-Prot Function:
Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. Transduces signals from CRK to activate RAS. Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1 (PubMed:12432078). 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.

Phenotypes From GWAS Catalog for RAPGEF1 Gene

Gene Ontology (GO) - Molecular Function for RAPGEF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity IEA,TAS --
GO:0005515 protein binding IPI 9748234
GO:0017034 Rap guanyl-nucleotide exchange factor activity IMP 21840392
GO:0017124 SH3 domain binding IEA --
genes like me logo Genes that share ontologies with RAPGEF1: view
genes like me logo Genes that share phenotypes with RAPGEF1: view

Animal Models for RAPGEF1 Gene

MGI Knock Outs for RAPGEF1:

Animal Model Products

CRISPR Products

miRNA for RAPGEF1 Gene

miRTarBase miRNAs that target RAPGEF1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RAPGEF1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RAPGEF1 Gene

Localization for RAPGEF1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RAPGEF1 Gene

Early endosome.

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 RAPGEF1 gene
Compartment Confidence
endosome 5
cytosol 5
nucleus 4
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for RAPGEF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 17515907
GO:0005768 endosome IEA --
GO:0005769 early endosome IEA,IDA 17724123
GO:0005829 cytosol TAS --
GO:0030670 phagocytic vesicle membrane IEA --
genes like me logo Genes that share ontologies with RAPGEF1: view

Pathways & Interactions for RAPGEF1 Gene

genes like me logo Genes that share pathways with RAPGEF1: view

Pathways by source for RAPGEF1 Gene

9 GeneGo (Thomson Reuters) pathways for RAPGEF1 Gene
  • Cytoskeleton remodeling FAK signaling
  • Development EPO-induced MAPK pathway
  • Development HGF signaling pathway
  • Development Neurotrophin family signaling
  • Development Thrombopoietin-regulated cell processes
6 Qiagen pathways for RAPGEF1 Gene
  • Epithelial Adherens Junctions
  • HGF Pathway
  • IGF1R Signaling
  • Molecular Mechanisms of Cancer
  • Paxillin Interactions

SIGNOR curated interactions for RAPGEF1 Gene

Is activated by:
Other effect:

Gene Ontology (GO) - Biological Process for RAPGEF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000186 activation of MAPKK activity TAS --
GO:0001568 blood vessel development IEA --
GO:0007165 signal transduction NAS 7512734
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway TAS 7512734
GO:0007264 small GTPase mediated signal transduction IEA --
genes like me logo Genes that share ontologies with RAPGEF1: view

Drugs & Compounds for RAPGEF1 Gene

No Compound Related Data Available

Transcripts for RAPGEF1 Gene

mRNA/cDNA for RAPGEF1 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RAPGEF1

Alternative Splicing Database (ASD) splice patterns (SP) for RAPGEF1 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18a · 18b ^ 19 ^ 20a ·
SP1: - - - - - - -
SP2: - - - - - -
SP3: - - -
SP4: - -
SP5:
SP6:
SP7:
SP8:

ExUns: 20b ^ 21a · 21b · 21c ^ 22 ^ 23a · 23b ^ 24 ^ 25 ^ 26 ^ 27 ^ 28a · 28b
SP1: -
SP2: -
SP3: -
SP4:
SP5:
SP6: -
SP7:
SP8:

Relevant External Links for RAPGEF1 Gene

GeneLoc Exon Structure for
RAPGEF1

Expression for RAPGEF1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RAPGEF1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RAPGEF1 Gene

This gene is overexpressed in Muscle - Skeletal (x4.6).

Protein differential expression in normal tissues from HIPED for RAPGEF1 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (23.3), CD8 Tcells (11.0), and Lymph node (10.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RAPGEF1 Gene



Protein tissue co-expression partners for RAPGEF1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RAPGEF1

SOURCE GeneReport for Unigene cluster for RAPGEF1 Gene:

Hs.127897

mRNA Expression by UniProt/SwissProt for RAPGEF1 Gene:

Q13905-RPGF1_HUMAN
Tissue specificity: Ubiquitously expressed in adult and fetus. Expression is high in adult skeletal muscle and placenta and in fetal brain and heart. Low levels of expression in adult and fetal liver.

Evidence on tissue expression from TISSUES for RAPGEF1 Gene

  • Liver(4.5)
  • Skin(4.5)
  • Spleen(4.5)
  • Nervous system(4)
  • Blood(2.8)
  • Kidney(2.8)
  • Heart(2.7)
  • Muscle(2.6)
  • Intestine(2.6)
  • Lymph node(2.3)
  • Adrenal gland(2.3)
  • Bone marrow(2.3)
  • Stomach(2.2)
  • Pancreas(2.1)
  • Lung(2)
genes like me logo Genes that share expression patterns with RAPGEF1: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for RAPGEF1 Gene

Orthologs for RAPGEF1 Gene

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

Orthologs for RAPGEF1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia RAPGEF1 30 31
  • 99.45 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia RAPGEF1 30 31
  • 90.28 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia RAPGEF1 30 31
  • 89 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rapgef1 30
  • 87.6 (n)
Mouse
(Mus musculus)
Mammalia Rapgef1 30 17 31
  • 87.13 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia RAPGEF1 31
  • 78 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia RAPGEF1 31
  • 76 (a)
OneToOne
Chicken
(Gallus gallus)
Aves RAPGEF1 30 31
  • 80.09 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia RAPGEF1 31
  • 89 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia rapgef1 30
  • 74.26 (n)
Str.2075 30
Zebrafish
(Danio rerio)
Actinopterygii rapgef1a 30 31
  • 69.18 (n)
OneToMany
rapgef1b 31
  • 68 (a)
OneToMany
zgc56372 30
Fruit Fly
(Drosophila melanogaster)
Insecta C3G 31
  • 26 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea Y34B4A.4 31
  • 31 (a)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SDC25 33
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 72 (a)
OneToOne
Species where no ortholog for RAPGEF1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • 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 RAPGEF1 Gene

ENSEMBL:
Gene Tree for RAPGEF1 (if available)
TreeFam:
Gene Tree for RAPGEF1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RAPGEF1: view image

Paralogs for RAPGEF1 Gene

(2) SIMAP similar genes for RAPGEF1 Gene using alignment to 14 proteins:

  • RPGF1_HUMAN
  • A5XEI4_HUMAN
  • A5XEI5_HUMAN
  • A5XEI6_HUMAN
  • A5XEI7_HUMAN
  • A5XEI8_HUMAN
  • A5XEI9_HUMAN
  • A5XEJ0_HUMAN
  • A5XEJ1_HUMAN
  • H0Y4V2_HUMAN
  • H0Y6R4_HUMAN
  • Q5JUE5_HUMAN
  • Q5JUE6_HUMAN
  • Q5JUE9_HUMAN
genes like me logo Genes that share paralogs with RAPGEF1: view

Variants for RAPGEF1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RAPGEF1 Gene

SNP ID Clinical significance and condition Chr 09 pos Variation AA Info Type
710212 Benign: not provided 131,596,338(-) C/T SYNONYMOUS_VARIANT
711399 Benign: not provided 131,629,161(-) C/T SYNONYMOUS_VARIANT
rs869025251 Uncertain Significance: Monoclonal B-Cell Lymphocytosis; not provided 131,621,989(-) T/C MISSENSE_VARIANT
VAR_069375 - p.Arg1012Gln

Additional dbSNP identifiers (rs#s) for RAPGEF1 Gene

Structural Variations from Database of Genomic Variants (DGV) for RAPGEF1 Gene

Variant ID Type Subtype PubMed ID
dgv1512e214 CNV gain 21293372
dgv4529e59 CNV duplication 20981092
esv2671200 CNV deletion 23128226
esv2739122 CNV deletion 23290073
esv2739123 CNV deletion 23290073
esv2739124 CNV deletion 23290073
esv2759718 CNV gain 17122850
esv3307312 CNV mobile element insertion 20981092
esv3621887 CNV loss 21293372
esv3621896 CNV gain 21293372
esv3621898 CNV gain 21293372
nsv518141 CNV gain 19592680
nsv615570 CNV loss 21841781
nsv6738 CNV insertion 18451855
nsv831742 CNV loss 17160897
nsv951792 CNV deletion 24416366

Variation tolerance for RAPGEF1 Gene

Residual Variation Intolerance Score: 5.87% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.86; 34.76% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RAPGEF1 Gene

Human Gene Mutation Database (HGMD)
RAPGEF1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RAPGEF1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RAPGEF1 Gene

Disorders for RAPGEF1 Gene

MalaCards: The human disease database

(3) MalaCards diseases for RAPGEF1 Gene - From: DISEASES

Disorder Aliases PubMed IDs
hemolytic uremic syndrome, atypical 1
  • hemolytic uremic syndrome, atypical, susceptibility to, 1
transient refractive change
macular degeneration, age-related, 1
  • macular degeneration, age-related, 2
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for RAPGEF1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with RAPGEF1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RAPGEF1 Gene

Publications for RAPGEF1 Gene

  1. RAPGEF1 gene variants associated with type 2 diabetes in the Korean population. (PMID: 19297053) Hong KW … Oh B (Diabetes research and clinical practice 2009) 3 23 41
  2. C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins. (PMID: 7512734) Tanaka S … Nagashima K (Proceedings of the National Academy of Sciences of the United States of America 1994) 2 3 4
  3. Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control. (PMID: 21840392) Pannekoek WJ … Bos JL (Cellular signalling 2011) 3 4
  4. Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder. (PMID: 20436929) Bithell A … Williams BP (PloS one 2010) 3 23
  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

Products for RAPGEF1 Gene

Sources for RAPGEF1 Gene