This gene is a member of the small GTPase superfamily and encodes a lipid-anchored, cell membrane protein with five repeats of the RAS-related GTP-binding region. This protein is vital in regulation of growth and cell cycle progression due to its role in the insulin/TOR/S6K signaling pathway. The protein has GTPase activity and shuttles between a GDP-bound form and a GTP-bound ... See more...

Aliases for RHEB Gene

Aliases for RHEB Gene

  • Ras Homolog, MTORC1 Binding 2 3 5
  • Ras Homolog Enriched In Brain 2 2 3
  • Ras Homolog Enriched In Brain 2 4
  • GTP-Binding Protein Rheb 3 4
  • RHEB2 3 4
  • RHEB 5

External Ids for RHEB Gene

Previous HGNC Symbols for RHEB Gene

  • RHEB2

Previous GeneCards Identifiers for RHEB Gene

  • GC07M150478
  • GC07M150555
  • GC07M150554
  • GC07M150600
  • GC07M150794
  • GC07M151163
  • GC07M144974

Summaries for RHEB Gene

Entrez Gene Summary for RHEB Gene

  • This gene is a member of the small GTPase superfamily and encodes a lipid-anchored, cell membrane protein with five repeats of the RAS-related GTP-binding region. This protein is vital in regulation of growth and cell cycle progression due to its role in the insulin/TOR/S6K signaling pathway. The protein has GTPase activity and shuttles between a GDP-bound form and a GTP-bound form, and farnesylation of the protein is required for this activity. Three pseudogenes have been mapped, two on chromosome 10 and one on chromosome 22. [provided by RefSeq, Jul 2008]

CIViC Summary for RHEB Gene

GeneCards Summary for RHEB Gene

RHEB (Ras Homolog, MTORC1 Binding) is a Protein Coding gene. Diseases associated with RHEB include Tuberous Sclerosis and Tuberous Sclerosis 1. Among its related pathways are Translation Translation regulation by Alpha-1 adrenergic receptors and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Gene Ontology (GO) annotations related to this gene include GTP binding and GTPase activity. An important paralog of this gene is RHEBL1.

UniProtKB/Swiss-Prot Summary for RHEB Gene

  • Activates the protein kinase activity of mTORC1, and thereby plays a role in the regulation of apoptosis. Stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. Has low intrinsic GTPase activity.

Gene Wiki entry for RHEB Gene

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

Genomics for RHEB Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RHEB 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 RHEB on the GeneHancer Hub at the UCSC Golden Path

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

Top Transcription factor binding sites by QIAGEN in the RHEB gene promoter:
  • Elk-1
  • GATA-2
  • p53

Genomic Locations for RHEB Gene

Genomic Locations for RHEB Gene
chr7:151,466,012-151,520,120
(GRCh38/hg38)
Size:
54,109 bases
Orientation:
Minus strand
chr7:151,163,098-151,217,206
(GRCh37/hg19)
Size:
54,109 bases
Orientation:
Minus strand

Genomic View for RHEB Gene

Genes around RHEB on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for RHEB Gene

Proteins for RHEB Gene

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

    Protein Symbol:
    Q15382-RHEB_HUMAN
    Recommended name:
    GTP-binding protein Rheb
    Protein Accession:
    Q15382
    Secondary Accessions:
    • B3KWN6
    • D3DX13
    • Q53Y56
    • Q99444

    Protein attributes for RHEB Gene

    Size:
    184 amino acids
    Molecular mass:
    20497 Da
    Quaternary structure:
    • Binds to mTORC1 in a guanyl nucleotide-independent manner. Interacts directly with MTOR, MLST8 and RPTOR. Interacts with TSC2. Interacts (when prenylated) with PDE6D; this promotes release from membranes.
    Miscellaneous:
    • The conserved catalytic Gln-64 found in other Ras-like GTPases seems not to be involved in GTP hydrolysis in RHEB.

    Three dimensional structures from OCA and Proteopedia for RHEB Gene

neXtProt entry for RHEB Gene

Post-translational modifications for RHEB Gene

  • Farnesylation is important for efficiently activating mTORC1-mediated signaling.
  • Phosphorylation by MAPKAPK5 impairs GTP-binding and inactivation.
  • Ubiquitination at Lys109, Lys135, Lys151, and Lys169
  • Modification sites at PhosphoSitePlus

Other Protein References for RHEB Gene

Antibody Products

  • Abcam antibodies for RHEB

Protein Products

  • Abcam proteins for RHEB

No data available for DME Specific Peptides for RHEB Gene

Domains & Families for RHEB Gene

Gene Families for RHEB Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted intracellular proteins

Protein Domains for RHEB Gene

InterPro:
Blocks:
  • Transforming protein P21 RAS signature
  • Ras small GTPase, Ras type
ProtoNet:

Suggested Antigen Peptide Sequences for RHEB Gene

GenScript: Design optimal peptide antigens:
  • Ras homolog enriched in brain (Q6NZ61_HUMAN)
  • Ras homolog enriched in brain (RHEB_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q15382

UniProtKB/Swiss-Prot:

RHEB_HUMAN :
  • Belongs to the small GTPase superfamily. Rheb family.
Family:
  • Belongs to the small GTPase superfamily. Rheb family.
genes like me logo Genes that share domains with RHEB: view

Function for RHEB Gene

Molecular function for RHEB Gene

UniProtKB/Swiss-Prot Function:
Activates the protein kinase activity of mTORC1, and thereby plays a role in the regulation of apoptosis. Stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. Has low intrinsic GTPase activity.
UniProtKB/Swiss-Prot EnzymeRegulation:
Alternates between an inactive form bound to GDP and an active form bound to GTP. Inactivated by TSC1-TSC2 via the GTPase activating protein (GAP) domain of TSC2.

Phenotypes From GWAS Catalog for RHEB Gene

Gene Ontology (GO) - Molecular Function for RHEB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0000287 magnesium ion binding IMP 15728574
GO:0003924 GTPase activity IEA,TAS --
GO:0005515 protein binding IPI 17301792
GO:0005525 GTP binding IEA,ISS --
genes like me logo Genes that share ontologies with RHEB: view
genes like me logo Genes that share phenotypes with RHEB: view

Animal Models for RHEB Gene

MGI Knock Outs for RHEB:
  • Rheb Rheb<tm1.1Yelg>
  • Rheb Rheb<tm1.1Pfw>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

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

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

Localization for RHEB Gene

Subcellular locations from UniProtKB/Swiss-Prot for RHEB Gene

Endomembrane system. Lipid-anchor. Cytoplasmic side. Golgi apparatus membrane. Lipid-anchor. Cytoplasmic side. Cytoplasm, cytosol. Endoplasmic reticulum membrane. Lipid-anchor. Cytoplasmic side.

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

Gene Ontology (GO) - Cellular Components for RHEB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005681 spliceosomal complex IEA --
GO:0005737 cytoplasm IEA --
GO:0005765 lysosomal membrane TAS --
GO:0005783 endoplasmic reticulum IEA --
genes like me logo Genes that share ontologies with RHEB: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for RHEB Gene

Pathways & Interactions for RHEB Gene

PathCards logo

SuperPathways for RHEB Gene

SuperPathway Contained pathways
1 Regulation of lipid metabolism Insulin signaling-generic cascades
.59
.59
.51
.44
.43
.34
2 mTOR signalling
3 RET signaling
4 AMP-activated Protein Kinase (AMPK) Signaling
5 Phospholipase D signaling pathway
genes like me logo Genes that share pathways with RHEB: view

Pathways by source for RHEB Gene

1 Sino Biological pathway for RHEB Gene
12 GeneGo (Thomson Reuters) pathways for RHEB Gene
  • Development CNTF receptor signaling
  • Development Endothelin-1/EDNRA transactivation of EGFR
  • Development Growth hormone signaling via PI3K/AKT and MAPK cascades
  • Development IGF-1 receptor signaling
  • Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis
3 R&D Systems pathways for RHEB Gene
1 Tocris pathway for RHEB Gene
2 Qiagen pathways for RHEB Gene
  • Molecular Mechanisms of Cancer
  • mTOR Pathway
1 Cell Signaling Technology pathway for RHEB Gene
1 GeneTex pathway for RHEB Gene

SIGNOR curated interactions for RHEB Gene

Activates:
Inactivates:
Is inactivated by:

Gene Ontology (GO) - Biological Process for RHEB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007050 cell cycle arrest TAS --
GO:0007165 signal transduction IEA,TAS 8661031
GO:0007264 small GTPase mediated signal transduction IBA 21873635
GO:0016241 regulation of macroautophagy TAS --
GO:0032006 regulation of TOR signaling IEA --
genes like me logo Genes that share ontologies with RHEB: view

Drugs & Compounds for RHEB Gene

(5) Drugs for RHEB Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Guanosine triphosphate Experimental Pharma Target 0
Guanosine diphosphate Experimental Pharma Target 0

(3) Additional Compounds for RHEB Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with RHEB: view

Transcripts for RHEB Gene

mRNA/cDNA for RHEB Gene

1 REFSEQ mRNAs :
13 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 RHEB

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

No ASD Table

Relevant External Links for RHEB Gene

GeneLoc Exon Structure for
RHEB

Expression for RHEB Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for RHEB Gene

This gene is overexpressed in Peripheral blood mononuclear cells (13.1).

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



Protein tissue co-expression partners for RHEB Gene

- Elite partner

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

SOURCE GeneReport for Unigene cluster for RHEB Gene:

Hs.283521

mRNA Expression by UniProt/SwissProt for RHEB Gene:

Q15382-RHEB_HUMAN
Tissue specificity: Ubiquitous. Highest levels observed in skeletal and cardiac muscle.

Evidence on tissue expression from TISSUES for RHEB Gene

  • Nervous system(4.9)
  • Skin(4.7)
  • Muscle(4.6)
  • Lung(3.7)
  • Kidney(3)
  • Liver(2.9)
  • Pancreas(2.9)
  • Blood(2.8)
  • Heart(2.8)
  • Eye(2.8)
  • Intestine(2.8)
  • Spleen(2.3)
  • Thyroid gland(2.3)
  • Bone marrow(2.3)
  • Adrenal gland(2.2)
  • Lymph node(2.2)
  • Stomach(2)
genes like me logo Genes that share expression patterns with RHEB: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for RHEB Gene

Orthologs for RHEB Gene

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

Orthologs for RHEB Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia RHEB 30 31
  • 99.82 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia RHEB 30 31
  • 94.93 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia RHEB 30 31
  • 94.38 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Rheb 30 17 31
  • 92.57 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rheb 30
  • 91.67 (n)
Chicken
(Gallus gallus)
Aves RHEB 30
  • 88.42 (n)
Lizard
(Anolis carolinensis)
Reptilia RHEB 31
  • 84 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia rheb 30
  • 83.7 (n)
Str.2304 30
African clawed frog
(Xenopus laevis)
Amphibia rheb-prov 30
Zebrafish
(Danio rerio)
Actinopterygii rheb 31
  • 86 (a)
OneToOne
zgc:73144 30
  • 79.71 (n)
zgc73144 30
Fruit Fly
(Drosophila melanogaster)
Insecta Rheb 31
  • 64 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea rheb-1 30 31
  • 50.1 (n)
OneToMany
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0A11330g 30
  • 54.12 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes RHB1 30 31 33
  • 51.12 (n)
OneToMany
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes rhb1 30
  • 56.16 (n)
Bread mold
(Neurospora crassa)
Ascomycetes NCU01444 30
  • 55.37 (n)
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.1999 30
Species where no ortholog for RHEB was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Squirt (Ciona savignyi)
  • 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 RHEB Gene

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

Paralogs for RHEB Gene

Pseudogenes.org Pseudogenes for RHEB Gene

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

Variants for RHEB Gene

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

SNP ID Clinical significance and condition Chr 07 pos Variation AA Info Type
rs1057519949 Likely Pathogenic: Renal cell carcinoma, papillary, 1; Transitional cell carcinoma of the bladder; Papillary renal cell carcinoma, sporadic; Malignant neoplasm of body of uterus 151,490,964(-) A/T MISSENSE_VARIANT
rs1057519950 Likely Pathogenic: Renal cell carcinoma, papillary, 1; Transitional cell carcinoma of the bladder; Papillary renal cell carcinoma, sporadic; Malignant neoplasm of body of uterus 151,490,963(-) T/C MISSENSE_VARIANT
rs1554438588 Likely Pathogenic: Hemimegalencephaly 151,490,948(-) T/A MISSENSE_VARIANT
VAR_036310 A colorectal cancer sample p.Glu139Lys

Additional dbSNP identifiers (rs#s) for RHEB Gene

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

Variant ID Type Subtype PubMed ID
dgv3695n106 OTHER inversion 24896259
esv3615481 CNV gain 21293372
esv3615482 CNV loss 21293372
nsv1067934 OTHER inversion 25765185
nsv1122179 CNV deletion 24896259
nsv1126820 CNV deletion 24896259
nsv1151906 OTHER inversion 26484159
nsv471954 CNV novel sequence insertion 20440878
nsv6006 CNV insertion 18451855
nsv818570 CNV gain 17921354
nsv824394 CNV gain 20364138
nsv831189 CNV gain 17160897
nsv970970 CNV duplication 23825009

Variation tolerance for RHEB Gene

Residual Variation Intolerance Score: 50.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.16; 3.68% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RHEB Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for RHEB Gene

MalaCards: The human disease database

(15) MalaCards diseases for RHEB Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
tuberous sclerosis
  • tuberous sclerosis 1
tuberous sclerosis 1
  • ts
kidney angiomyolipoma
  • angiomyolipoma of kidney
subependymal glioma
  • mixed subependymoma-ependymoma
renal cell carcinoma, papillary, 1
  • rccp1
- elite association - COSMIC cancer census association via MalaCards
Search RHEB in MalaCards View complete list of genes associated with diseases

Additional Disease Information for RHEB

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 RHEB: view

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

Publications for RHEB Gene

  1. Rheb binds and regulates the mTOR kinase. (PMID: 15854902) Long X … Avruch J (Current biology : CB 2005) 2 3 4 23
  2. Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1. (PMID: 16098514) Tee AR … Proud CG (FEBS letters 2005) 3 4 23
  3. Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. (PMID: 15340059) Li Y … Guan KL (Molecular and cellular biology 2004) 3 4 23
  4. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. (PMID: 12869586) Inoki K … Guan KL (Genes & development 2003) 3 4 23
  5. Isolation of cDNA and genomic clones of a human Ras-related GTP-binding protein gene and its chromosomal localization to the long arm of chromosome 7, 7q36. (PMID: 8661031) Mizuki N … Inoko H (Genomics 1996) 2 3 4

Products for RHEB Gene

Sources for RHEB Gene