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RB1 (retinoblastoma)

Written1999-09Dietmar R Lohmann
Institut fuer Humangenetik, Hufelandstr. 55, D-45122 Essen, Germany

(Note : for Links provided by Atlas : click)

Identity

Other nameshuman retinoblastoma suspectibility gene
HGNC (Hugo) RB1
LocusID (NCBI) 5925
Atlas_Id 90
Location 13q14.2  [Link to chromosome band 13q14]
Location_base_pair Starts at 48877883 and ends at 49056026 bp from pter ( according to hg19-Feb_2009)  [Mapping RB1.png]
Fusion genes
(updated 2016)
BBX (3q13.12) / RB1 (13q14.2)FNDC3A (13q14.2) / RB1 (13q14.2)ITM2B (13q14.2) / RB1 (13q14.2)
RB1 (13q14.2) / C14orf166 (14q22.1)RB1 (13q14.2) / CNIH3 (1q42.12)RB1 (13q14.2) / ITM2B (13q14.2)
RB1 (13q14.2) / KCNRG (13q14.2)RB1 (13q14.2) / MED4 (13q14.2)RB1 (13q14.2) / MICAL1 (6q21)
RB1 (13q14.2) / RB1 (13q14.2)RB1 (13q14.2) / TMEM65 (8q24.13)RCBTB2 (13q14.2) / RB1 (13q14.2)
SH3PXD2A (10q24.33) / RB1 (13q14.2)VWA8 (13q14.11) / RB1 (13q14.2)

DNA/RNA

 
  c-RB1 at 13q14 in normal cells: PAC 825K22 (top) and PAC 971H14 (bottom) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Description 27 exons spanning 180 kb
Transcription 4.7 kb mRNA, 2.7 kb open reading frame, 2 kb 3-UTR

Protein

Description 928aa nuclear phosphoprotein; 110 kDa; pRB is phosphorylated by members of the cyclin-dependent kinase (cdk) system prior to the entry into S-phase; hypophosphorylated pRB binds to members of the E2F family of transcription factors; binding to E2F is mediated by by two domains within pRB (pocket domains)
Expression ubiquitous
Localisation nucleus
Function cell cycle regulation, differentiation
Homology pRB, p107, and p130 constitute a small family of nuclear proteins with significant sequence similarity in two discontinuous areas (pockets domains); conditional on the phosphorylation status, these pocket proteins can bind transforming proteins of DNA tumor viruses as well as nuclear proteins

Mutations

Germinal germline mutations in the RB1 gene are causative for hereditary predisposition to retinoblastoma; the spectrum of predisposing mutations includes large deletions (about 20%), single base substitutions (about 50%) and small length mutations (about 30%); most mutations are associated with almost complete penetrance: some rare alleles show incomplete penetrace and reduced expressivity (low penetrance retinoblastoma)
Somatic in retinoblastomas, both RB1 alleles are mutated; in addtion to the mutational spectrum of germinal mutations, retinoblastomas can show loss of heterozygosity and hypermethylation at the CpG-island associated with the 5'-end of the RB1 gene

Implicated in

Note
Entity Retinoblastoma
Disease hereditary predisposition to retinoblastoma formation in carrieres of a germinal mutation
somatic inactivation of both RB1 alleles can result in sporadic unilateral retinobalstoma
  
Entity Sarcomas
Disease carriers of a germinal RB1gene mutation are predisposed to soft tissue sarcomas and osteogenic sarcomas
somatic inactivation of both RB1 alleles observed in some sarcomas
  
Entity various cancers
Disease RB1 gene mutations have been observed in several tumor entities. In lung cancer there is a notable high frequency of RB1 gene mutations although no increased incidence of these tumors has been observed in carriers of a germinal RB1 gene mutation.
  

Bibliography

The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F.
Hiebert SW, Chellappan SP, Horowitz JM, Nevins JR
Genes & development. 1992 ; 6 (2) : 177-185.
PMID 1531329
 
The retinoblastoma protein is phosphorylated on multiple sites by human cdc2.
Lees JA, Buchkovich KJ, Marshak DR, Anderson CW, Harlow E
The EMBO journal. 1991 ; 10 (13) : 4279-4290.
PMID 1756735
 
Genomic organization of the human retinoblastoma gene.
T'Ang A, Wu KJ, Hashimoto T, Liu WY, Takahashi R, Shi XH, Mihara K, Zhang FH, Chen YY, Du C
Oncogene. 1989 ; 4 (4) : 401-407.
PMID 2717184
 
RB kinases and RB-binding proteins: new points of view.
Taya Y
Trends in biochemical sciences. 1997 ; 22 (1) : 14-17.
PMID 9020586
 
Complete genomic sequence of the human retinoblastoma susceptibility gene.
Toguchida J, McGee TL, Paterson JC, Eagle JR, Tucker S, Yandell DW, Dryja TP
Genomics. 1993 ; 17 (3) : 535-543.
PMID 7902321
 
The retinoblastoma protein and cell cycle control.
Weinberg RA
Cell. 1995 ; 81 (3) : 323-330.
PMID 7736585
 

Citation

This paper should be referenced as such :
Lohmann, DR
RB1 (retinoblastoma)
Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):137-138.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RB1ID90.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 12 ]
  Chronic myelogenous leukaemia (CML)
del(13q) in ALL
del(13q) in myeloid malignancies
del (13q)
del(13q) in multiple myeloma
del(13q) in non-Hodgkin's lymphoma
Multiple myeloma
Plasma cell leukemia (PCL)
Small lymphocytic lymphoma
t(5;7)(q35;q21) TLX3/CDK6
t(2;7)(p11;q21) IGK/CDK6;t(7;14)(q21;q32) IGH/CDK6;t(7;22)(q21;q11) IGL/CDK6
+13,+13 or tetrasomy 13

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 27 ]
  Nervous system: Astrocytic tumors
Bladder: Urothelial carcinomas
Bone: Chondrosarcoma
Bone: Conventional Osteosarcoma
Eye tumors: an overview
Head and Neck: Squamous cell carcinoma: an overview
Head and Neck: Epidermoid carcinoma
Liver: Hepatocellular carcinoma
Head and Neck: Laryngeal tumors: an overview
Head and Neck: Laryngeal squamous cell carcinoma
Lung: Non-small cell carcinoma
Lung: small cell cancer
Testis: Germ cell tumors
Head and Neck: Oral squamous cell carcinoma
Bone: Osteosarcoma
Ovarian tumours : an overview
Ovary: Choriocarcinoma
Nervous system: Peripheral nerve sheath tumors
Neuro-Endocrine/Endocrine System: Pituitary adenomas
Head and neck: Retinoblastoma
Eye: Retinoma
Soft Tissues: Rhabdomyosarcoma
Skin: Melanoma
Soft tissue tumors: an overview
Squamous cell cancer
Lung: Translocations in Small Cell Carcinoma
Lung: Translocations in Squamous Cell Carcinoma
Eye: Posterior uveal melanoma

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Retinoblastoma

External links

Nomenclature
HGNC (Hugo)RB1   9884
Cards
AtlasRB1ID90
Entrez_Gene (NCBI)RB1  5925  retinoblastoma 1
AliasesOSRC; PPP1R130; RB; p105-Rb; 
pRb; pp110
GeneCards (Weizmann)RB1
Ensembl hg19 (Hinxton)ENSG00000139687 [Gene_View]  chr13:48877883-49056026 [Contig_View]  RB1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000139687 [Gene_View]  chr13:48877883-49056026 [Contig_View]  RB1 [Vega]
ICGC DataPortalENSG00000139687
TCGA cBioPortalRB1
AceView (NCBI)RB1
Genatlas (Paris)RB1
WikiGenes5925
SOURCE (Princeton)RB1
Genomic and cartography
GoldenPath hg19 (UCSC)RB1  -     chr13:48877883-49056026 +  13q14.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)RB1  -     13q14.2   [Description]    (hg38-Dec_2013)
EnsemblRB1 - 13q14.2 [CytoView hg19]  RB1 - 13q14.2 [CytoView hg38]
Mapping of homologs : NCBIRB1 [Mapview hg19]  RB1 [Mapview hg38]
OMIM109800   180200   182280   259500   614041   
Gene and transcription
Genbank (Entrez)AB208788 AF043224 AK291258 AK299179 AK300284
RefSeq transcript (Entrez)NM_000321
RefSeq genomic (Entrez)NC_000013 NC_018924 NG_009009 NT_024524 NW_004929388
Consensus coding sequences : CCDS (NCBI)RB1
Cluster EST : UnigeneHs.408528 [ NCBI ]
CGAP (NCI)Hs.408528
Alternative Splicing GalleryENSG00000139687
Gene ExpressionRB1 [ NCBI-GEO ]   RB1 [ EBI - ARRAY_EXPRESS ]   RB1 [ SEEK ]   RB1 [ MEM ]
Gene Expression Viewer (FireBrowse)RB1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5925
GTEX Portal (Tissue expression)RB1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP06400 (Uniprot)
NextProtP06400  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP06400
Splice isoforms : SwissVarP06400 (Swissvar)
PhosPhoSitePlusP06400
Domains : Interpro (EBI)Cyclin-like    RB1    RB_A    RB_B    RB_C    RB_fam    RB_N   
Domain families : Pfam (Sanger)DUF3452 (PF11934)    RB_A (PF01858)    RB_B (PF01857)    Rb_C (PF08934)   
Domain families : Pfam (NCBI)pfam11934    pfam01858    pfam01857    pfam08934   
Domain families : Smart (EMBL)CYCLIN (SM00385)  
DMDM Disease mutations5925
Blocks (Seattle)RB1
PDB (SRS)1AD6    1GH6    1GUX    1H25    1N4M    1O9K    1PJM    2AZE    2QDJ    2R7G    3N5U    3POM    4CRI    4ELJ    4ELL   
PDB (PDBSum)1AD6    1GH6    1GUX    1H25    1N4M    1O9K    1PJM    2AZE    2QDJ    2R7G    3N5U    3POM    4CRI    4ELJ    4ELL   
PDB (IMB)1AD6    1GH6    1GUX    1H25    1N4M    1O9K    1PJM    2AZE    2QDJ    2R7G    3N5U    3POM    4CRI    4ELJ    4ELL   
PDB (RSDB)1AD6    1GH6    1GUX    1H25    1N4M    1O9K    1PJM    2AZE    2QDJ    2R7G    3N5U    3POM    4CRI    4ELJ    4ELL   
Structural Biology KnowledgeBase1AD6    1GH6    1GUX    1H25    1N4M    1O9K    1PJM    2AZE    2QDJ    2R7G    3N5U    3POM    4CRI    4ELJ    4ELL   
SCOP (Structural Classification of Proteins)1AD6    1GH6    1GUX    1H25    1N4M    1O9K    1PJM    2AZE    2QDJ    2R7G    3N5U    3POM    4CRI    4ELJ    4ELL   
CATH (Classification of proteins structures)1AD6    1GH6    1GUX    1H25    1N4M    1O9K    1PJM    2AZE    2QDJ    2R7G    3N5U    3POM    4CRI    4ELJ    4ELL   
SuperfamilyP06400
Human Protein AtlasENSG00000139687
Peptide AtlasP06400
HPRD01574
IPIIPI00302829   IPI01010522   IPI00383682   
Protein Interaction databases
DIP (DOE-UCLA)P06400
IntAct (EBI)P06400
FunCoupENSG00000139687
BioGRIDRB1
STRING (EMBL)RB1
ZODIACRB1
Ontologies - Pathways
QuickGOP06400
Ontology : AmiGOcell cycle checkpoint  G1/S transition of mitotic cell cycle  regulation of transcription involved in G1/S transition of mitotic cell cycle  chromatin  core promoter binding  RNA polymerase II activating transcription factor binding  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription coactivator activity  protein binding  nucleus  nucleoplasm  spindle  chromatin remodeling  transcription, DNA-templated  negative regulation of protein kinase activity  cell cycle arrest  negative regulation of transcription from RNA polymerase II promoter during mitosis  mitotic cell cycle checkpoint  Ras protein signal transduction  regulation of mitotic cell cycle  positive transcription elongation factor complex b  transcription factor binding  viral process  SWI/SNF complex  PML body  kinase binding  androgen receptor signaling pathway  sister chromatid biorientation  neuron projection development  ubiquitin protein ligase binding  maintenance of mitotic sister chromatid cohesion  glial cell apoptotic process  Rb-E2F complex  skeletal muscle cell differentiation  neuron maturation  identical protein binding  enucleate erythrocyte differentiation  negative regulation of sequence-specific DNA binding transcription factor activity  regulation of lipid kinase activity  myoblast differentiation  positive regulation of macrophage differentiation  positive regulation of mitotic metaphase/anaphase transition  negative regulation of smoothened signaling pathway  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  digestive tract development  cell morphogenesis involved in neuron differentiation  negative regulation of epithelial cell proliferation  androgen receptor binding  striated muscle cell differentiation  phosphoprotein binding  cell division  neuron apoptotic process  protein localization to chromosome, centromeric region  cellular response to xenobiotic stimulus  regulation of cohesin localization to chromatin  negative regulation of transcription involved in G1/S transition of mitotic cell cycle  regulation of centromere complex assembly  hepatocyte apoptotic process  negative regulation of G1/S transition of mitotic cell cycle  
Ontology : EGO-EBIcell cycle checkpoint  G1/S transition of mitotic cell cycle  regulation of transcription involved in G1/S transition of mitotic cell cycle  chromatin  core promoter binding  RNA polymerase II activating transcription factor binding  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription coactivator activity  protein binding  nucleus  nucleoplasm  spindle  chromatin remodeling  transcription, DNA-templated  negative regulation of protein kinase activity  cell cycle arrest  negative regulation of transcription from RNA polymerase II promoter during mitosis  mitotic cell cycle checkpoint  Ras protein signal transduction  regulation of mitotic cell cycle  positive transcription elongation factor complex b  transcription factor binding  viral process  SWI/SNF complex  PML body  kinase binding  androgen receptor signaling pathway  sister chromatid biorientation  neuron projection development  ubiquitin protein ligase binding  maintenance of mitotic sister chromatid cohesion  glial cell apoptotic process  Rb-E2F complex  skeletal muscle cell differentiation  neuron maturation  identical protein binding  enucleate erythrocyte differentiation  negative regulation of sequence-specific DNA binding transcription factor activity  regulation of lipid kinase activity  myoblast differentiation  positive regulation of macrophage differentiation  positive regulation of mitotic metaphase/anaphase transition  negative regulation of smoothened signaling pathway  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  digestive tract development  cell morphogenesis involved in neuron differentiation  negative regulation of epithelial cell proliferation  androgen receptor binding  striated muscle cell differentiation  phosphoprotein binding  cell division  neuron apoptotic process  protein localization to chromosome, centromeric region  cellular response to xenobiotic stimulus  regulation of cohesin localization to chromatin  negative regulation of transcription involved in G1/S transition of mitotic cell cycle  regulation of centromere complex assembly  hepatocyte apoptotic process  negative regulation of G1/S transition of mitotic cell cycle  
Pathways : BIOCARTACyclins and Cell Cycle Regulation [Genes]    Regulation of p27 Phosphorylation during Cell Cycle Progression [Genes]    Influence of Ras and Rho proteins on G1 to S Transition [Genes]    Cell Cycle: G1/S Check Point [Genes]    Human Cytomegalovirus and Map Kinase Pathways [Genes]    Overview of telomerase RNA component gene hTerc Transcriptional Regulation [Genes]    Cyclin E Destruction Pathway [Genes]    p53 Signaling Pathway [Genes]    Regulation of transcriptional activity by PML [Genes]    Telomeres, Telomerase, Cellular Aging, and Immortality [Genes]    Tumor Suppressor Arf Inhibits Ribosomal Biogenesis [Genes]    FAS signaling pathway ( CD95 ) [Genes]    RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage [Genes]    E2F1 Destruction Pathway [Genes]    TNFR1 Signaling Pathway [Genes]    BTG family proteins and cell cycle regulation [Genes]    HIV-I Nef: negative effector of Fas and TNF [Genes]    Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) [Genes]    Chaperones modulate interferon Signaling Pathway [Genes]   
Pathways : KEGGCell cycle    Hepatitis B    HTLV-I infection    Epstein-Barr virus infection    Pathways in cancer    Viral carcinogenesis    Pancreatic cancer    Glioma    Prostate cancer    Melanoma    Bladder cancer    Chronic myeloid leukemia    Small cell lung cancer    Non-small cell lung cancer   
REACTOMEP06400 [protein]
REACTOME PathwaysR-HSA-68949 Orc1 removal from chromatin [pathway]
REACTOME PathwaysR-HSA-69231 Cyclin D associated events in G1 [pathway]
REACTOME PathwaysR-HSA-2559584 Formation of Senescence-Associated Heterochromatin Foci (SAHF) [pathway]
REACTOME PathwaysR-HSA-69200 Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes [pathway]
REACTOME PathwaysR-HSA-68949 Orc1 removal from chromatin [pathway]
REACTOME PathwaysR-HSA-69202 Cyclin E associated events during G1/S transition [pathway]
REACTOME PathwaysR-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry [pathway]
REACTOME PathwaysR-HSA-2299718 Condensation of Prophase Chromosomes [pathway]
REACTOME PathwaysR-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1 [pathway]
NDEx NetworkRB1
Atlas of Cancer Signalling NetworkRB1
Wikipedia pathwaysRB1
Orthology - Evolution
OrthoDB5925
GeneTree (enSembl)ENSG00000139687
Phylogenetic Trees/Animal Genes : TreeFamRB1
Homologs : HomoloGeneRB1
Homology/Alignments : Family Browser (UCSC)RB1
Gene fusions - Rearrangements
Fusion : MitelmanBBX/RB1 [3q13.12/13q14.2]  [t(3;13)(q13;q14)]  
Fusion : MitelmanFNDC3A/RB1 [13q14.2/13q14.2]  [t(13;13)(q14;q14)]  
Fusion : MitelmanITM2B/RB1 [13q14.2/13q14.2]  [t(13;13)(q14;q14)]  
Fusion : MitelmanRB1/CNIH3 [13q14.2/1q42.12]  [t(1;13)(q42;q14)]  
Fusion : MitelmanRB1/ITM2B [13q14.2/13q14.2]  [t(13;13)(q14;q14)]  
Fusion : MitelmanRB1/KCNRG [13q14.2/13q14.2]  [t(13;13)(q14;q14)]  
Fusion : MitelmanRB1/MED4 [13q14.2/13q14.2]  [t(13;13)(q14;q14)]  
Fusion : MitelmanRCBTB2/RB1 [13q14.2/13q14.2]  [t(13;13)(q14;q14)]  
Fusion : MitelmanSH3PXD2A/RB1 [10q24.33/13q14.2]  [t(10;13)(q24;q14)]  
Fusion : MitelmanVWA8/RB1 [13q14.11/13q14.2]  [t(13;13)(q14;q14)]  
Fusion: TCGABBX 3q13.12 RB1 13q14.2 BRCA
Fusion: TCGAFNDC3A 13q14.2 RB1 13q14.2 BRCA
Fusion: TCGAKIAA0564 RB1 13q14.2 BRCA
Fusion: TCGARB1 13q14.2 CNIH3 1q42.12 LUSC
Fusion: TCGARB1 13q14.2 KCNRG 13q14.2 OV
Fusion: TCGARB1 13q14.2 MED4 13q14.2 SKCM
Fusion: TCGARCBTB2 13q14.2 RB1 13q14.2 BRCA
Fusion: TCGASH3PXD2A 10q24.33 RB1 13q14.2 OV
Polymorphisms : SNP, variants
NCBI Variation ViewerRB1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RB1
dbVarRB1
ClinVarRB1
1000_GenomesRB1 
Exome Variant ServerRB1
ExAC (Exome Aggregation Consortium)RB1 (select the gene name)
Genetic variants : HAPMAP5925
Genomic Variants (DGV)RB1 [DGVbeta]
Mutations
ICGC Data PortalRB1 
TCGA Data PortalRB1 
Broad Tumor PortalRB1
OASIS PortalRB1 [ Somatic mutations - Copy number]
Cancer Gene: CensusRB1 
Somatic Mutations in Cancer : COSMICRB1 
intOGen PortalRB1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)rb1-lsdb
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
BioMutasearch RB1
DgiDB (Drug Gene Interaction Database)RB1
DoCM (Curated mutations)RB1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RB1 (select a term)
intoGenRB1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)13:48877883-49056026  ENSG00000139687
CONAN: Copy Number AnalysisRB1 
Mutations and Diseases : HGMDRB1
OMIM109800    180200    182280    259500    614041   
MedgenRB1
Genetic Testing Registry RB1
NextProtP06400 [Medical]
TSGene5925
GENETestsRB1
Huge Navigator RB1 [HugePedia]
snp3D : Map Gene to Disease5925
BioCentury BCIQRB1
ClinGenRB1 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5925
Chemical/Pharm GKB GenePA295
Drug Sensitivity RB1
Clinical trialRB1
Miscellaneous
canSAR (ICR)RB1 (select the gene name)
Other databaseRB1-gene mutation database
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=RB1
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRB1
EVEXRB1
GoPubMedRB1
iHOPRB1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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