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Aliases for RAPGEF4 Gene

Aliases for RAPGEF4 Gene

  • Rap Guanine Nucleotide Exchange Factor 4 2 3 5
  • CAMP-Regulated Guanine Nucleotide Exchange Factor II 2 3 4
  • Exchange Protein Directly Activated By CAMP 2 2 3 4
  • RAP Guanine-Nucleotide-Exchange Factor (GEF) 4 2 3
  • Rap Guanine Nucleotide Exchange Factor (GEF) 4 2 3
  • Exchange Factor Directly Activated By CAMP 2 3 4
  • CAMP-GEFII 3 4
  • EPAC 2 3 4
  • CGEF2 3 4
  • EPAC2 3 4
  • Putative Protein Product Of Nbla00496 3
  • Nbla00496 3
  • EPAC 3

External Ids for RAPGEF4 Gene

Previous GeneCards Identifiers for RAPGEF4 Gene

  • GC02P173804
  • GC02P173426
  • GC02P173308
  • GC02P173600
  • GC02P165478

Summaries for RAPGEF4 Gene

GeneCards Summary for RAPGEF4 Gene

RAPGEF4 (Rap Guanine Nucleotide Exchange Factor 4) is a Protein Coding gene. Diseases associated with RAPGEF4 include Lesch-Nyhan Syndrome and Acrodysostosis. Among its related pathways are Phospholipase D signaling pathway and G-protein signaling G-Protein alpha-i signaling cascades. GO annotations related to this gene include guanyl-nucleotide exchange factor activity and Ras GTPase binding. An important paralog of this gene is RAPGEF3.

UniProtKB/Swiss-Prot for RAPGEF4 Gene

  • Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2 (By similarity).

Gene Wiki entry for RAPGEF4 Gene

No data available for Entrez Gene Summary , CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RAPGEF4 Gene

Genomics for RAPGEF4 Gene

Regulatory Elements for RAPGEF4 Gene

Enhancers for RAPGEF4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02G172994 1.1 Ensembl ENCODE 12.4 +260.8 260840 2.4 ELF3 FOXA2 FEZF1 THRB RARA ELK1 SCRT2 FOS CEBPB CEBPA RAPGEF4 GC02P173050 ALDH7A1P2
GH02G172782 1 Ensembl ENCODE 11 +47.8 47848 1.6 CTCF MXI1 SAP130 MAX RAD21 ZBTB40 ZFHX2 GATA3 GATA2 NR2F6 RAPGEF4 RAPGEF4-AS1 GC02P172797
GH02G173002 0.9 ENCODE 10.5 +267.9 267917 1.0 FOXA2 ATF1 FEZF1 ZSCAN9 RARA CREM MIXL1 ZNF263 ZNF398 PPARG RAPGEF4 GC02P173050 ALDH7A1P2
GH02G172984 1.3 Ensembl ENCODE dbSUPER 7.2 +250.1 250082 2.0 TBP PKNOX1 RFX5 ZNF366 SCRT2 FOS CEBPB TSHZ1 ZEB2 HNF4A MAP3K20 RAPGEF4 GC02P173050 ALDH7A1P2
GH02G172654 0.9 Ensembl ENCODE 10.3 -79.4 -79371 2.3 FOXA2 BHLHE40 JUND ELK1 BCL6B FOS NFE2 MAFK NFE2L2 RAPGEF4 RAPGEF4-AS1 PDK1 GC02M172611 ENSG00000199866 GC02M172559
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around RAPGEF4 on UCSC Golden Path with GeneCards custom track

Promoters for RAPGEF4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000126363 526 401 MAZ MXI1 RFX1 RNF2 SUZ12 RBBP5 KLF9 EZH2

Genomic Location for RAPGEF4 Gene

Chromosome:
2
Start:
172,735,274 bp from pter
End:
173,052,893 bp from pter
Size:
317,620 bases
Orientation:
Plus strand

Genomic View for RAPGEF4 Gene

Genes around RAPGEF4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RAPGEF4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RAPGEF4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RAPGEF4 Gene

Proteins for RAPGEF4 Gene

  • Protein details for RAPGEF4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WZA2-RPGF4_HUMAN
    Recommended name:
    Rap guanine nucleotide exchange factor 4
    Protein Accession:
    Q8WZA2
    Secondary Accessions:
    • B2R7R3
    • B7Z283
    • B7Z3T6
    • B7Z912
    • O95636
    • Q8IXK6
    • Q8TAA4

    Protein attributes for RAPGEF4 Gene

    Size:
    1011 amino acids
    Molecular mass:
    115522 Da
    Quaternary structure:
    • Interacts with RIMS1 and RIMS2. Probably part of a complex with RIMS2 and GTP-activated RAB3A (By similarity).

    Alternative splice isoforms for RAPGEF4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RAPGEF4 Gene

Post-translational modifications for RAPGEF4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for RAPGEF4 Gene

Domains & Families for RAPGEF4 Gene

Gene Families for RAPGEF4 Gene

IUPHAR :

Graphical View of Domain Structure for InterPro Entry

Q8WZA2

UniProtKB/Swiss-Prot:

RPGF4_HUMAN :
  • The N-terminal nucleotide phosphate binding region cAMP 1 has a much lower affinity for cAMP as compared to cAMP 2.
Domain:
  • The N-terminal nucleotide phosphate binding region cAMP 1 has a much lower affinity for cAMP as compared to cAMP 2.
  • The DEP domain is involved in membrane localization independent from regulation by cAMP.
genes like me logo Genes that share domains with RAPGEF4: view

Function for RAPGEF4 Gene

Molecular function for RAPGEF4 Gene

UniProtKB/Swiss-Prot Function:
Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2 (By similarity).

Gene Ontology (GO) - Molecular Function for RAPGEF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity TAS,EXP 15334074
GO:0005088 Ras guanyl-nucleotide exchange factor activity ISS --
GO:0005515 protein binding IPI 11438518
GO:0017016 Ras GTPase binding ISS --
GO:0030552 cAMP binding ISS --
genes like me logo Genes that share ontologies with RAPGEF4: view
genes like me logo Genes that share phenotypes with RAPGEF4: view

Animal Models for RAPGEF4 Gene

MGI Knock Outs for RAPGEF4:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RAPGEF4 Gene

Localization for RAPGEF4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RAPGEF4 Gene

Cytoplasm. Membrane; Peripheral membrane protein.

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 RAPGEF4 gene
Compartment Confidence
plasma membrane 5
cytosol 4
nucleus 3
extracellular 2
cytoskeleton 2
endoplasmic reticulum 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for RAPGEF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IEA --
GO:0005886 plasma membrane TAS --
GO:0016020 membrane TAS 10777494
genes like me logo Genes that share ontologies with RAPGEF4: view

Pathways & Interactions for RAPGEF4 Gene

genes like me logo Genes that share pathways with RAPGEF4: view

Gene Ontology (GO) - Biological Process for RAPGEF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006887 exocytosis IEA --
GO:0007186 G-protein coupled receptor signaling pathway TAS 9856955
GO:0007264 small GTPase mediated signal transduction IEA --
GO:0017156 calcium ion regulated exocytosis IEA --
GO:0017157 regulation of exocytosis IEA --
genes like me logo Genes that share ontologies with RAPGEF4: view

No data available for SIGNOR curated interactions for RAPGEF4 Gene

Drugs & Compounds for RAPGEF4 Gene

(9) Drugs for RAPGEF4 Gene - From: ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cyclic amp Experimental Pharma 0
Guanosine diphosphate Experimental Pharma 0
Guanosine monophosphate Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0
HJC 0350 Pharma 0

(4) ApexBio Compounds for RAPGEF4 Gene

Compound Action Cas Number
8-CPT-2Me-cAMP, sodium salt EPAC agonist, selective 634207-53-7
HJC 0350 885434-70-8
MitMAB 1119-97-7
OctMAB 1120-02-1
genes like me logo Genes that share compounds with RAPGEF4: view

Drug Products

Transcripts for RAPGEF4 Gene

Unigene Clusters for RAPGEF4 Gene

Rap guanine nucleotide exchange factor (GEF) 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for RAPGEF4 Gene

No ASD Table

Relevant External Links for RAPGEF4 Gene

GeneLoc Exon Structure for
RAPGEF4
ECgene alternative splicing isoforms for
RAPGEF4

Expression for RAPGEF4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RAPGEF4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RAPGEF4 Gene

This gene is overexpressed in Brain - Hippocampus (x8.8), Brain - Anterior cingulate cortex (BA24) (x7.6), Brain - Amygdala (x7.5), Brain - Cortex (x6.8), and Brain - Frontal Cortex (BA9) (x6.1).

Protein differential expression in normal tissues from HIPED for RAPGEF4 Gene

This gene is overexpressed in Platelet (34.8) and Frontal cortex (19.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for RAPGEF4 Gene



Protein tissue co-expression partners for RAPGEF4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of RAPGEF4 Gene:

RAPGEF4

SOURCE GeneReport for Unigene cluster for RAPGEF4 Gene:

Hs.470646

mRNA Expression by UniProt/SwissProt for RAPGEF4 Gene:

Q8WZA2-RPGF4_HUMAN
Tissue specificity: Predominantly expressed in brain and adrenal gland. Isoform 2 is expressed in liver. Isoform 1 is expressed in liver at very low levels.

Evidence on tissue expression from TISSUES for RAPGEF4 Gene

  • Nervous system(5)
  • Adrenal gland(2.4)
  • Pancreas(2.4)
  • Heart(2.3)
  • Muscle(2.3)
genes like me logo Genes that share expression patterns with RAPGEF4: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for RAPGEF4 Gene

Orthologs for RAPGEF4 Gene

This gene was present in the common ancestor of animals.

Orthologs for RAPGEF4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RAPGEF4 34 35
  • 99.5 (n)
oppossum
(Monodelphis domestica)
Mammalia RAPGEF4 35
  • 95 (a)
OneToOne
cow
(Bos Taurus)
Mammalia RAPGEF4 34 35
  • 94.66 (n)
dog
(Canis familiaris)
Mammalia RAPGEF4 34 35
  • 94.64 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia RAPGEF4 35
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Rapgef4 34 16 35
  • 91.53 (n)
rat
(Rattus norvegicus)
Mammalia Rapgef4 34
  • 87.84 (n)
chicken
(Gallus gallus)
Aves RAPGEF4 34
  • 83.47 (n)
lizard
(Anolis carolinensis)
Reptilia RAPGEF4 35
  • 88 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rapgef4 34
  • 77.5 (n)
zebrafish
(Danio rerio)
Actinopterygii RAPGEF4 (1 of 2) 35
  • 79 (a)
OneToMany
rapgef4 34 35
  • 71.95 (n)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4614 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007307 34
  • 54.99 (n)
fruit fly
(Drosophila melanogaster)
Insecta Epac 34 35
  • 53.54 (n)
worm
(Caenorhabditis elegans)
Secernentea epac-1 34 35
  • 47.32 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 40 (a)
OneToMany
Species where no ortholog for RAPGEF4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • 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)
  • 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 RAPGEF4 Gene

ENSEMBL:
Gene Tree for RAPGEF4 (if available)
TreeFam:
Gene Tree for RAPGEF4 (if available)

Paralogs for RAPGEF4 Gene

genes like me logo Genes that share paralogs with RAPGEF4: view

Variants for RAPGEF4 Gene

Sequence variations from dbSNP and Humsavar for RAPGEF4 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs1000012561 -- 173,030,104(+) CTCTA(A/T)TTTTT intron-variant
rs1000028886 -- 172,852,722(+) TCTTA(A/G)GGGAA intron-variant
rs1000040026 -- 173,035,185(+) AAATA(A/G)CCTCC intron-variant
rs1000040869 -- 172,759,555(+) AGCCG(C/T)TGTGA intron-variant
rs1000041917 -- 172,802,948(+) CTCAT(A/G)TTCAG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RAPGEF4 Gene

Variant ID Type Subtype PubMed ID
esv2668640 CNV deletion 23128226
esv2678314 CNV deletion 23128226
esv2721145 CNV deletion 23290073
esv2721146 CNV deletion 23290073
esv2760591 CNV gain 21179565
esv2762295 CNV loss 21179565
esv3303237 CNV mobile element insertion 20981092
esv3327085 CNV insertion 20981092
esv3357537 CNV insertion 20981092
esv3560555 CNV deletion 23714750
esv3593374 CNV loss 21293372
esv3593375 CNV loss 21293372
esv5188 CNV loss 18987735
nsv471833 CNV novel sequence insertion 20440878
nsv483123 CNV gain 15286789
nsv583665 CNV gain 21841781
nsv834459 CNV gain 17160897

Variation tolerance for RAPGEF4 Gene

Residual Variation Intolerance Score: 10.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.74; 46.84% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for RAPGEF4 Gene

Human Gene Mutation Database (HGMD)
RAPGEF4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RAPGEF4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RAPGEF4 Gene

Disorders for RAPGEF4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for RAPGEF4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
lesch-nyhan syndrome
  • complete hypoxanthine-guanine phosphoribosyltransferase deficiency
acrodysostosis
  • acrodysplasia
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for RAPGEF4

Genetic Association Database (GAD)
RAPGEF4
Human Genome Epidemiology (HuGE) Navigator
RAPGEF4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
RAPGEF4
genes like me logo Genes that share disorders with RAPGEF4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RAPGEF4 Gene

Publications for RAPGEF4 Gene

  1. Characterization of the gene EPAC2: structure, chromosomal localization, tissue expression, and identification of the liver- specific isoform. (PMID: 11707077) Ueno H. … Seino S. (Genomics 2001) 3 4 22 64
  2. Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. (PMID: 10777494) de Rooij J. … Bos J.L. (J. Biol. Chem. 2000) 2 3 4 64
  3. A family of cAMP-binding proteins that directly activate rap1. (PMID: 9856955) Kawasaki H. … Graybiel A.M. (Science 1998) 2 3 4 64
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose J.E. … Uhl G.R. (Mol. Med. 2010) 3 46 64
  5. High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility. (PMID: 19401682) Maestrini E. … Monaco A.P. (Mol. Psychiatry 2010) 3 46 64

Products for RAPGEF4 Gene

Sources for RAPGEF4 Gene

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