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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 Response to elevated platelet cytosolic Ca2+ and Innate Immune System. Gene Ontology (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

Additional gene information 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

GeneHancer (GH) Regulatory Elements for RAPGEF4 Gene

Promoters and enhancers for RAPGEF4 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
GH02I172735 Promoter 1.4 EPDnew Ensembl 550.8 +0.5 527 0.4 MXI1 MAZ RFX1 RNF2 SUZ12 ZNF335 ZFX ZBTB26 EZH2 RAPGEF4-AS1 RAPGEF4 GC02P172713
GH02I172928 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE 550.1 +193.1 193100 1.9 ZBTB21 ZIC2 ZNF664 POLR2A ZSCAN5C PRDM10 ZBTB20 MAZ CEBPB ATF2 RAPGEF4 ALDH7A1P2 GC02P173050
GH02I172857 Promoter/Enhancer 1.3 EPDnew Ensembl ENCODE 550.1 +124.4 124395 4.7 MEIS2 PKNOX1 ZNF10 ZNF384 ZBTB40 PRDM6 POLR2A STAT3 RCOR1 ZBTB17 RAPGEF4 ALDH7A1P2 GC02P172797
GH02I172887 Promoter 0.6 EPDnew 550.1 +152.4 152436 0.1 ZNF189 RAPGEF4 ALDH7A1P2 GC02P172797
GH02I172821 Promoter 0.5 EPDnew 550.2 +86.3 86324 0.1 RAPGEF4 GC02P172797 ALDH7A1P2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around RAPGEF4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the RAPGEF4 gene promoter:

Genomic Locations for RAPGEF4 Gene

Genomic Locations for RAPGEF4 Gene
chr2:172,735,274-173,052,893
(GRCh38/hg38)
Size:
317,620 bases
Orientation:
Plus strand
chr2:173,600,002-173,917,621
(GRCh37/hg19)

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

No Post-translational modifications

No data available for DME Specific Peptides for RAPGEF4 Gene

Domains & Families for RAPGEF4 Gene

Gene Families for RAPGEF4 Gene

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

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).

Phenotypes From GWAS Catalog for RAPGEF4 Gene

Gene Ontology (GO) - Molecular Function for RAPGEF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity EXP,TAS 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

Clone 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
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Focal adhesion sites (2)
See all subcellular structures

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:

Clone 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)
  • Heart(2.4)
  • Muscle(2.4)
  • Pancreas(2.4)
genes like me logo Genes that share expression patterns with RAPGEF4: view

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 33 34
  • 99.5 (n)
oppossum
(Monodelphis domestica)
Mammalia RAPGEF4 34
  • 95 (a)
OneToOne
cow
(Bos Taurus)
Mammalia RAPGEF4 33 34
  • 94.66 (n)
dog
(Canis familiaris)
Mammalia RAPGEF4 33 34
  • 94.64 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia RAPGEF4 34
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Rapgef4 33 16 34
  • 91.53 (n)
rat
(Rattus norvegicus)
Mammalia Rapgef4 33
  • 87.84 (n)
chicken
(Gallus gallus)
Aves RAPGEF4 33
  • 83.47 (n)
lizard
(Anolis carolinensis)
Reptilia RAPGEF4 34
  • 88 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rapgef4 33
  • 77.5 (n)
zebrafish
(Danio rerio)
Actinopterygii RAPGEF4 (1 of 2) 34
  • 79 (a)
OneToMany
rapgef4 33 34
  • 71.95 (n)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4614 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007307 33
  • 54.99 (n)
fruit fly
(Drosophila melanogaster)
Insecta Epac 33 34
  • 53.54 (n)
worm
(Caenorhabditis elegans)
Secernentea epac-1 33 34
  • 47.32 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 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 Variation AA Info Type
rs1000012561 -- 173,030,104(+) A/T intron_variant
rs1000028886 -- 172,852,722(+) G/A genic_upstream_transcript_variant, intron_variant
rs1000040026 -- 173,035,185(+) G/A intron_variant
rs1000040869 -- 172,759,555(+) C/T genic_upstream_transcript_variant, intron_variant
rs1000041917 -- 172,802,948(+) A/G genic_upstream_transcript_variant, intron_variant

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

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

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)

Additional Variant Information 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: HGMD, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
lesch-nyhan syndrome
  • lns
acrodysostosis
  • acrodysplasia
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for RAPGEF4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 58
  2. Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. (PMID: 10777494) de Rooij J … Bos JL (The Journal of biological chemistry 2000) 2 3 4 58
  3. A family of cAMP-binding proteins that directly activate Rap1. (PMID: 9856955) Kawasaki H … Graybiel AM (Science (New York, N.Y.) 1998) 2 3 4 58
  4. 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 44 58
  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 … IMGSAC (Molecular psychiatry 2010) 3 44 58

Products for RAPGEF4 Gene

Sources for RAPGEF4 Gene

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