RB1 (retinoblastoma)

1999-09-01   Dietmar R Lohmann 

Institut fuer Humangenetik, Hufelandstr. 55, D-45122 Essen, Germany

Identity

HGNC
LOCATION
13q14.2
IMAGE
Atlas Image
LEGEND
RB1 (retinoblastoma) Hybridization with Vysis LSI 13 (13q14) SpectrumOrange/ 13q34 SpectrumGreen probe (Abbott Molecular, US) showing the RB1 gene on 13q14.2 (red signals) - Courtesy Adriana Zamecnikova.
LOCUSID
ALIAS
OSRC,PPP1R130,RB,p105-Rb,p110-RB1,pRb,pp110
FUSION GENES

DNA/RNA

Description

27 exons spanning 180 kb
Atlas Image
c-RB1 at 13q14 in normal cells: PAC 825K22 (top) and PAC 971H14 (bottom) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

Transcription

4.7 kb mRNA, 2.7 kb open reading frame, 2 kb 3-UTR

Proteins

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

Entity name
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 name
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 name
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

Pubmed IDLast YearTitleAuthors
15313291992The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F.Hiebert SW et al
17567351991The retinoblastoma protein is phosphorylated on multiple sites by human cdc2.Lees JA et al
27171841989Genomic organization of the human retinoblastoma gene.T'Ang A et al
90205861997RB kinases and RB-binding proteins: new points of view.Taya Y et al
79023211993Complete genomic sequence of the human retinoblastoma susceptibility gene.Toguchida J et al
77365851995The retinoblastoma protein and cell cycle control.Weinberg RA et al

Other Information

Locus ID:

NCBI: 5925
MIM: 614041
HGNC: 9884
Ensembl: ENSG00000139687

Variants:

dbSNP: 5925
ClinVar: 5925
TCGA: ENSG00000139687
COSMIC: RB1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000139687ENST00000267163P06400
ENSG00000139687ENST00000267163A0A024RDV3
ENSG00000139687ENST00000467505Q92728
ENSG00000139687ENST00000643064A0A2R8Y743
ENSG00000139687ENST00000646097A0A2R8YFL6
ENSG00000139687ENST00000650461A0A3B3IS71

Expression (GTEx)

0
10
20
30
40
50
60
70

Pathways

PathwaySourceExternal ID
Cell cycleKEGGko04110
Pancreatic cancerKEGGko05212
GliomaKEGGko05214
Prostate cancerKEGGko05215
MelanomaKEGGko05218
Bladder cancerKEGGko05219
Chronic myeloid leukemiaKEGGko05220
Small cell lung cancerKEGGko05222
Non-small cell lung cancerKEGGko05223
Cell cycleKEGGhsa04110
Pathways in cancerKEGGhsa05200
Pancreatic cancerKEGGhsa05212
GliomaKEGGhsa05214
Prostate cancerKEGGhsa05215
MelanomaKEGGhsa05218
Bladder cancerKEGGhsa05219
Chronic myeloid leukemiaKEGGhsa05220
Small cell lung cancerKEGGhsa05222
Non-small cell lung cancerKEGGhsa05223
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
Hepatitis BKEGGhsa05161
Cell cycle - G1/S transitionKEGGhsa_M00692
Cell cycle - G1/S transitionKEGGM00692
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic G1-G1/S phasesREACTOMER-HSA-453279
G1 PhaseREACTOMER-HSA-69236
Cyclin D associated events in G1REACTOMER-HSA-69231
G1/S TransitionREACTOMER-HSA-69206
Cyclin E associated events during G1/S transitionREACTOMER-HSA-69202
Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexesREACTOMER-HSA-69200
E2F mediated regulation of DNA replicationREACTOMER-HSA-113510
Inhibition of replication initiation of damaged DNA by RB1/E2F1REACTOMER-HSA-113501
S PhaseREACTOMER-HSA-69242
Cyclin A:Cdk2-associated events at S phase entryREACTOMER-HSA-69656
Synthesis of DNAREACTOMER-HSA-69239
Switching of origins to a post-replicative stateREACTOMER-HSA-69052
Orc1 removal from chromatinREACTOMER-HSA-68949
Regulation of DNA replicationREACTOMER-HSA-69304
Removal of licensing factors from originsREACTOMER-HSA-69300
M PhaseREACTOMER-HSA-68886
Mitotic ProphaseREACTOMER-HSA-68875
Condensation of Prophase ChromosomesREACTOMER-HSA-2299718
DNA ReplicationREACTOMER-HSA-69306
Cellular responses to stressREACTOMER-HSA-2262752
Cellular SenescenceREACTOMER-HSA-2559583
DNA Damage/Telomere Stress Induced SenescenceREACTOMER-HSA-2559586
Formation of Senescence-Associated Heterochromatin Foci (SAHF)REACTOMER-HSA-2559584
Endocrine resistanceKEGGko01522
Endocrine resistanceKEGGhsa01522
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA445538RetinoblastomaDiseaseDataAnnotation, Literature, MultilinkAnnotationassociated23788249

References

Pubmed IDYearTitleCitations
128096022003Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence.715
124597292002The retinoblastoma tumour suppressor in development and cancer.227
153068142004Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control.204
269284632016Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer.190
199266382010Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer.182
175768132007BNIP3 is an RB/E2F target gene required for hypoxia-induced autophagy.162
257585282015RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer.147
210991102010The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression.141
170285782006Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce irreversible cellular senescence.135
187948992008E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8.121

Citation

Dietmar R Lohmann

RB1 (retinoblastoma)

Atlas Genet Cytogenet Oncol Haematol. 1999-09-01

Online version: http://atlasgeneticsoncology.org/gene/90/rb1