The protein encoded by this gene is a guanine nucleotide exchange factor that activates the oncogenes HRAS and RAP1A. Defects in this gene have been associated with systemic lupus erythematosus and several cancers. [provided by RefSeq, Mar 2017] See more...

Aliases for RASGRP3 Gene

Aliases for RASGRP3 Gene

  • RAS Guanyl Releasing Protein 3 2 3 5
  • GRP3 2 3 4
  • Calcium- And Diacylglycerol-Regulated Guanine Nucleotide Exchange Factor III 2 3
  • Calcium And DAG-Regulated Guanine Nucleotide Exchange Factor III 3 4
  • RAS Guanyl Releasing Protein 3 (Calcium And DAG-Regulated) 2 3
  • Guanine Nucleotide Exchange Factor For Rap1 3 4
  • Ras Guanyl-Releasing Protein 3 3 4
  • CalDAG-GEFIII 2 3
  • KIAA0846 2 4
  • RASGRP3 5

External Ids for RASGRP3 Gene

Previous GeneCards Identifiers for RASGRP3 Gene

  • GC02P033619
  • GC02P033635
  • GC02P033573
  • GC02P033514
  • GC02P033395
  • GC02P033661

Summaries for RASGRP3 Gene

Entrez Gene Summary for RASGRP3 Gene

  • The protein encoded by this gene is a guanine nucleotide exchange factor that activates the oncogenes HRAS and RAP1A. Defects in this gene have been associated with systemic lupus erythematosus and several cancers. [provided by RefSeq, Mar 2017]

GeneCards Summary for RASGRP3 Gene

RASGRP3 (RAS Guanyl Releasing Protein 3) is a Protein Coding gene. Diseases associated with RASGRP3 include Bleeding Disorder, Platelet-Type, 18 and Systemic Lupus Erythematosus. Among its related pathways are RET signaling and G-protein signaling M-RAS regulation pathway. Gene Ontology (GO) annotations related to this gene include calcium ion binding and GTPase activator activity. An important paralog of this gene is RASGRP1.

UniProtKB/Swiss-Prot Summary for RASGRP3 Gene

Gene Wiki entry for RASGRP3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RASGRP3 Gene

Genomics for RASGRP3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RASGRP3 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J033474 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 275.1 +41.5 41502 6.1 BCLAF1 NCOR1 IKZF1 MYC ZNF600 POLR2A ZNF10 ZIC2 YY1 CTCF RASGRP3 MN297643 LTBP1 TTC27 HSALNG0014115 lnc-LTBP1-1 FAM98A
GH02J033437 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE 250.7 +1.1 1076 2.4 NCOR1 IKZF1 JUND REST TAL1 RUNX1 NFE2 ATF1 FOXM1 MAFK RASGRP3 lnc-LTBP1-1 MN297643 FAM98A
GH02J033405 Promoter/Enhancer 0.5 EPDnew Ensembl 261.7 -30.5 -30523 0.8 RASGRP3 MIR4430 piR-61101-378 LTBP1
GH02J033529 Enhancer 1.1 Ensembl ENCODE dbSUPER 25 +94.2 94205 5.9 BCLAF1 JUND YY1 EBF1 RAD21 ASH2L SPI1 EHMT2 BATF MAFK HSALNG0014116 RASGRP3 HSALNG0014115 FAM98A
GH02J033552 Enhancer 1 Ensembl ENCODE dbSUPER 27.7 +119.9 119877 9.6 ETS1 SPI1 MAX POLR2A FOXA1 ZNF652 HNF4A BHLHE40 EGR1 NFIL3 MK280144-354 RASGRP3 HSALNG0014118 RASGRP3-AS1 HSALNG0014116 FAM98A
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RASGRP3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RASGRP3

Top Transcription factor binding sites by QIAGEN in the RASGRP3 gene promoter:
  • aMEF-2
  • CUTL1
  • MEF-2A
  • NF-kappaB
  • NF-kappaB1
  • Sox5
  • SRF
  • SRF (504 AA)
  • SRY
  • STAT5A

Genomic Locations for RASGRP3 Gene

Latest Assembly
128,427 bases
Plus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
128,384 bases
Plus strand

(GRCh37/hg19 by Ensembl)
128,427 bases
Plus strand

Genomic View for RASGRP3 Gene

Genes around RASGRP3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RASGRP3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RASGRP3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RASGRP3 Gene

Proteins for RASGRP3 Gene

  • Protein details for RASGRP3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Ras guanyl-releasing protein 3
    Protein Accession:
    Secondary Accessions:
    • D6W583
    • O94931
    • Q53SD7

    Protein attributes for RASGRP3 Gene

    690 amino acids
    Molecular mass:
    78332 Da
    Quaternary structure:
    No Data Available
    • Sequence=BAA74869.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for RASGRP3 Gene


neXtProt entry for RASGRP3 Gene

Post-translational modifications for RASGRP3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for RASGRP3 Gene

Domains & Families for RASGRP3 Gene

Gene Families for RASGRP3 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for RASGRP3 Gene

Suggested Antigen Peptide Sequences for RASGRP3 Gene

GenScript: Design optimal peptide antigens:
  • Guanine nucleotide exchange factor for Rap1 (GRP3_HUMAN)
  • RAS guanyl releasing protein 3 (Calcium and DAG-regulated), isoform CRA_b (Q53SD7_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the RASGRP family.
  • Belongs to the RASGRP family.
genes like me logo Genes that share domains with RASGRP3: view

Function for RASGRP3 Gene

Molecular function for RASGRP3 Gene

UniProtKB/Swiss-Prot Function:
Guanine nucleotide exchange factor (GEF) for Ras and Rap1.

Phenotypes From GWAS Catalog for RASGRP3 Gene

Gene Ontology (GO) - Molecular Function for RASGRP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity IEA,TAS --
GO:0005096 GTPase activator activity IEA,IDA 10934204
GO:0005509 calcium ion binding IEA,NAS 10934204
GO:0005515 protein binding IPI 25416956
GO:0019900 kinase binding IEA --
genes like me logo Genes that share ontologies with RASGRP3: view
genes like me logo Genes that share phenotypes with RASGRP3: view

Animal Models for RASGRP3 Gene

MGI Knock Outs for RASGRP3:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RASGRP3

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RASGRP3 Gene

Localization for RASGRP3 Gene

Subcellular locations from

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 RASGRP3 gene
Compartment Confidence
plasma membrane 5
cytosol 3
mitochondrion 2
nucleus 2
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RASGRP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane NAS 10934204
GO:0032045 guanyl-nucleotide exchange factor complex IEA --
GO:0048471 perinuclear region of cytoplasm IEA --
genes like me logo Genes that share ontologies with RASGRP3: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for RASGRP3 Gene

Pathways & Interactions for RASGRP3 Gene

PathCards logo

SuperPathways for RASGRP3 Gene

SuperPathway Contained pathways
1 RET signaling
2 Downstream signaling events of B Cell Receptor (BCR)
3 B cell receptor signaling pathway (KEGG)
4 Ras signaling pathway
5 Developmental Biology
genes like me logo Genes that share pathways with RASGRP3: view

Pathways by source for RASGRP3 Gene

4 GeneGo (Thomson Reuters) pathways for RASGRP3 Gene
  • G-protein signaling M-RAS regulation pathway
  • G-protein signaling TC21 regulation pathway
  • G-protein signaling_H-RAS regulation pathway
  • G-protein signaling_Rap1A regulation pathway
1 Qiagen pathway for RASGRP3 Gene
  • ITK and TCR Signaling
2 Cell Signaling Technology pathways for RASGRP3 Gene

SIGNOR curated interactions for RASGRP3 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for RASGRP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade NAS,TAS --
GO:0007264 small GTPase mediated signal transduction IEA,TAS 10934204
GO:0007265 Ras protein signal transduction IEA --
GO:0035556 intracellular signal transduction IEA --
GO:0043087 regulation of GTPase activity IEA --
genes like me logo Genes that share ontologies with RASGRP3: view

Drugs & Compounds for RASGRP3 Gene

(3) Drugs for RASGRP3 Gene - From: 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

(4) Additional Compounds for RASGRP3 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • 1-Palmitoyl-2-lignoceroyl-sn-glycerol
  • DAG(16:0/24:0)
  • DAG(40:0)
  • DG(16:0/24:0)
  • DG(40:0)
Diglycerides Group B
  • Diglyceride
  • DG(32:4)
  • DG(14:1/18:3)
  • DAG(14:1/18:3)
  • Diacylglycerol(32:4)
Diglycerides Group C
  • (2S)-1-Hydroxy-3-(palmitoyloxy)propan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
  • 1,2-DG 16:0/20:4(omega-6)
  • 1-Hexadecanoyl-2-(5Z,8Z,11Z,14Z)-icosatetraenoyl-sn-glycerol
  • 1-Hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol
  • DAG(16:0/20:4)
91125-76-7, 29541-66-0, 51621-26-2
Diglycerides Group D
  • 1,2-Di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycerol
  • 1,2-Didocosahexaenoyl-sn-glycerol
  • DAG(22:6/22:6)
  • DAG(22:6N3/22:6N3)
  • DAG(22:6OMEGA3/22:6OMEGA3)
genes like me logo Genes that share compounds with RASGRP3: view

Transcripts for RASGRP3 Gene

mRNA/cDNA for RASGRP3 Gene

11 NCBI additional mRNA sequence :
18 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RASGRP3

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for RASGRP3 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11a · 11b · 11c · 11d ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b ^ 18 ^ 19a ·
SP1: - - - - - - - - -
SP2: - - - - -
SP3: - -
SP4: - - - - - - - -
SP5: - - - - -
SP6: - -
SP7: - - - - - - -
SP8: - - -
SP9: -

ExUns: 19b ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25a · 25b · 25c
SP1: -
SP2: -
SP3: -

Relevant External Links for RASGRP3 Gene

GeneLoc Exon Structure for

Expression for RASGRP3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RASGRP3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RASGRP3 Gene

This gene is overexpressed in Brain - Spinal cord (cervical c-1) (x7.7).

Protein differential expression in normal tissues from HIPED for RASGRP3 Gene

This gene is overexpressed in Heart (37.4) and Liver (31.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for RASGRP3 Gene

Protein tissue co-expression partners for RASGRP3 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RASGRP3

SOURCE GeneReport for Unigene cluster for RASGRP3 Gene:


Evidence on tissue expression from TISSUES for RASGRP3 Gene

  • Nervous system(4.3)
  • Heart(2.3)
  • Lymph node(2.2)
genes like me logo Genes that share expression patterns with RASGRP3: view

Primer products for research

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for RASGRP3 Gene

Orthologs for RASGRP3 Gene

This gene was present in the common ancestor of animals.

Orthologs for RASGRP3 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia RASGRP3 29 30
  • 99.71 (n)
(Canis familiaris)
Mammalia RASGRP3 29 30
  • 93.81 (n)
(Bos Taurus)
Mammalia RASGRP3 29 30
  • 93.47 (n)
(Mus musculus)
Mammalia Rasgrp3 29 16 30
  • 89.28 (n)
(Monodelphis domestica)
Mammalia RASGRP3 30
  • 89 (a)
(Ornithorhynchus anatinus)
Mammalia RASGRP3 30
  • 88 (a)
(Rattus norvegicus)
Mammalia Rasgrp3 29
  • 87.87 (n)
(Gallus gallus)
Aves RASGRP3 29 30
  • 80.49 (n)
(Anolis carolinensis)
Reptilia RASGRP3 30
  • 86 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia rasgrp3 29
  • 75 (n)
(Danio rerio)
Actinopterygii rasgrp3 29 30
  • 70.5 (n)
(Caenorhabditis elegans)
Secernentea rgef-1 29 30
  • 50.19 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 42 (a)
Species where no ortholog for RASGRP3 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)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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 RASGRP3 Gene

Gene Tree for RASGRP3 (if available)
Gene Tree for RASGRP3 (if available)
Evolutionary constrained regions (ECRs) for RASGRP3: view image
Alliance of Genome Resources:
Additional Orthologs for RASGRP3

Paralogs for RASGRP3 Gene

(5) SIMAP similar genes for RASGRP3 Gene using alignment to 7 proteins:

  • C9J9C9_HUMAN
  • C9K0P4_HUMAN
  • H7C352_HUMAN
genes like me logo Genes that share paralogs with RASGRP3: view

Variants for RASGRP3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RASGRP3 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs1574485216 Likely Benign: not provided 33,549,712(+) C/T
NM_001139488.2(RASGRP3):c.1503C>T (p.Thr501=)
rs189837410 Benign: not provided 33,522,003(+) C/T
NM_001139488.2(RASGRP3):c.417C>T (p.Ser139=)
rs2124437 Association: Lip and oral cavity carcinoma 33,457,670(+) G/T
rs781152306 Likely Benign: not provided 33,520,009(+) C/T
NM_001139488.2(RASGRP3):c.231C>T (p.Phe77=)
rs13388394 -- p.Thr393Ala

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for RASGRP3 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for RASGRP3 Gene

Variant ID Type Subtype PubMed ID
dgv1885n106 CNV deletion 24896259
dgv444n27 CNV loss 19166990
dgv6755n54 CNV loss 21841781
dgv6756n54 CNV loss 21841781
dgv684e214 CNV loss 21293372
esv2199255 CNV deletion 18987734
esv2462414 CNV deletion 19546169
esv2661374 CNV deletion 23128226
esv2719890 CNV deletion 23290073
esv2762447 CNV gain 21179565
esv28690 CNV gain+loss 19812545
esv3554711 CNV deletion 23714750
esv3583713 CNV loss 25503493
esv3590286 CNV loss 21293372
esv3590288 CNV loss 21293372
esv3590289 CNV loss 21293372
esv3590291 CNV gain 21293372
esv3590295 CNV loss 21293372
esv3891725 CNV gain 25118596
esv4426 CNV loss 18987735
nsv1072406 CNV deletion 25765185
nsv1120122 OTHER inversion 24896259
nsv1123309 CNV deletion 24896259
nsv1127719 CNV deletion 24896259
nsv433177 CNV loss 18776910
nsv435723 CNV deletion 17901297
nsv516338 CNV loss 19592680
nsv517737 CNV loss 19592680
nsv581310 CNV loss 21841781
nsv819369 CNV gain 19587683
nsv820684 CNV deletion 20802225
nsv828775 CNV loss 20364138
nsv955027 CNV deletion 24416366

Variation tolerance for RASGRP3 Gene

Residual Variation Intolerance Score: 36.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.84; 67.16% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RASGRP3 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for
Leiden Open Variation Database (LOVD)

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RASGRP3 Gene

Disorders for RASGRP3 Gene

MalaCards: The human disease database

(2) MalaCards diseases for RASGRP3 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
bleeding disorder, platelet-type, 18
  • bdplt18
systemic lupus erythematosus
  • sle
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for RASGRP3

Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with RASGRP3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RASGRP3 Gene

Publications for RASGRP3 Gene

  1. 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) 2 3 4 22
  2. Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PMID: 10048485) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1998) 2 3 4
  3. 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 40
  4. TNIP1, SLC15A4, ETS1, RasGRP3 and IKZF1 are associated with clinical features of systemic lupus erythematosus in a Chinese Han population. (PMID: 20516000) He CF … Yang S (Lupus 2010) 3 40
  5. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. (PMID: 19838193) Han JW … Zhang XJ (Nature genetics 2009) 3 40

Products for RASGRP3 Gene

Sources for RASGRP3 Gene