RB1
RB transcriptional corepressor 1, the group of Receptor ligands
Basic information
Region (hg38): 13:48303744-48599436
Previous symbols: [ "OSRC" ]
Links
Phenotypes
GenCC
Source:
- hereditary retinoblastoma (Strong), mode of inheritance: AD
- hereditary retinoblastoma (Supportive), mode of inheritance: AD
- hereditary retinoblastoma (Definitive), mode of inheritance: AD
- melanoma (Moderate), mode of inheritance: AD
- hereditary retinoblastoma (Definitive), mode of inheritance: AD
- retinoblastoma (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Retinoblastoma | AD | Oncologic | Frequent and regular eye examination (including under anesthesia if necessary) starting in infancy is indicated in order to detect ocular neoplasms, which may allow early detection and treatment; Awareness of the risk of additional neoplasms may allow early detection and treatment based on signs/symptoms (eg, bone pain); Limiting exposure to DNA-damaging agents (including high-dose radiotherapy) may be beneficial | Oncologic | 1066869; 268552; 6930517; 6654325; 6696673; 2876425; 2885916; 2895471; 3175621; 7795591; 8651278; 9311732; 10502774; 10561222; 11097606; 11449317; 11709011; 11382640; 11382638; 12096963; 12523888; 12541220; 12488270; 12598449; 14996857; 16936756; 16631255; 16606893; 17613328; 17096365; 19280657; 20301625; 21150892; 22084214; 22103627; 22237022; 22293180; 22355046 |
ClinVar
This is a list of variants' phenotypes submitted to
- Retinoblastoma (580 variants)
- Hereditary cancer-predisposing syndrome (161 variants)
- not provided (54 variants)
- Malignant tumor of urinary bladder (7 variants)
- RB1-related disorder (5 variants)
- Hypotrichosis 8 (4 variants)
- Hereditary retinoblastoma (3 variants)
- Neoplasm (3 variants)
- Squamous cell carcinoma (1 variants)
- Small cell lung carcinoma (1 variants)
- Lynch syndrome 4 (1 variants)
- Lung adenocarcinoma (1 variants)
- See cases (1 variants)
- Wooly hair, autosomal recessive 1, with or without hypotrichosis (1 variants)
- Trilateral retinoblastoma (1 variants)
- Retinoblastoma;Bone osteosarcoma;Malignant tumor of urinary bladder;Small cell lung carcinoma (1 variants)
- Vulvar adenocarcinoma of mammary gland type (1 variants)
- Malignant tumor of urinary bladder;Retinoblastoma;Bone osteosarcoma;Small cell lung carcinoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RB1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 498 | 507 | ||||
| missense | 11 | 22 | 1175 | 28 | 1241 | |
| nonsense | 162 | 169 | ||||
| start loss | 2 | |||||
| frameshift | 354 | 365 | ||||
| inframe indel | 29 | 36 | ||||
| splice donor/acceptor (+/-2bp) | 132 | 22 | 158 | |||
| splice region | 14 | 16 | 77 | 121 | 3 | 231 |
| non coding | 12 | 131 | 399 | 117 | 668 | |
| Total | 671 | 68 | 1355 | 928 | 124 |
Highest pathogenic variant AF is 0.0000981
Variants in RB1
This is a list of pathogenic ClinVar variants found in the RB1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 13-48303745-G-A | Retinoblastoma | Uncertain significance (Dec 15, 2023) | ||
| 13-48303748-C-T | Retinoblastoma | Uncertain significance (Jan 18, 2024) | ||
| 13-48303753-T-C | Retinoblastoma | Uncertain significance (Jan 28, 2024) | ||
| 13-48303755-G-A | Retinoblastoma | Uncertain significance (Dec 29, 2023) | ||
| 13-48303756-C-G | Retinoblastoma | Uncertain significance (Dec 12, 2023) | ||
| 13-48303757-C-A | Retinoblastoma | Uncertain significance (Jun 14, 2016) | ||
| 13-48303758-G-C | Retinoblastoma | Uncertain significance (Apr 06, 2018) | ||
| 13-48303760-G-C | RB1-related disorder | Uncertain significance (Sep 29, 2022) | ||
| 13-48303760-G-T | Retinoblastoma | Uncertain significance (Jun 14, 2016) | ||
| 13-48303761-C-T | Retinoblastoma | Uncertain significance (Nov 24, 2023) | ||
| 13-48303762-G-A | Uncertain significance (Nov 09, 2023) | |||
| 13-48303764-G-T | Retinoblastoma • not specified • Hereditary cancer-predisposing syndrome • Malignant tumor of urinary bladder | Conflicting classifications of pathogenicity (Feb 14, 2024) | ||
| 13-48303766-G-A | Retinoblastoma | Uncertain significance (Jan 16, 2024) | ||
| 13-48303779-G-T | Retinoblastoma | Uncertain significance (Jan 18, 2024) | ||
| 13-48303785-C-G | Retinoblastoma | Uncertain significance (Dec 20, 2023) | ||
| 13-48303787-C-T | Retinoblastoma | Uncertain significance (Jan 02, 2024) | ||
| 13-48303788-A-G | Retinoblastoma | Uncertain significance (Dec 21, 2023) | ||
| 13-48303788-A-T | Retinoblastoma | Uncertain significance (Jan 17, 2024) | ||
| 13-48303790-G-A | Retinoblastoma | Uncertain significance (Jan 24, 2024) | ||
| 13-48303792-G-A | Retinoblastoma | Uncertain significance (Jan 05, 2024) | ||
| 13-48303813-A-T | Retinoblastoma | Uncertain significance (Mar 30, 2018) | ||
| 13-48303815-G-A | Retinoblastoma | Uncertain significance (Jan 03, 2024) | ||
| 13-48303828-G-C | Retinoblastoma | Uncertain significance (Jan 02, 2024) | ||
| 13-48303831-CG-C | Retinoblastoma | Uncertain significance (Dec 28, 2023) | ||
| 13-48303832-G-A | Retinoblastoma | Uncertain significance (Jan 12, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RB1 | protein_coding | protein_coding | ENST00000267163 | 27 | 178236 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 2.33e-8 | 125681 | 0 | 5 | 125686 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.67 | 311 | 475 | 0.655 | 0.0000238 | 6073 |
| Missense in Polyphen | 86 | 186.59 | 0.4609 | 2409 | ||
| Synonymous | 0.488 | 152 | 160 | 0.951 | 0.00000782 | 1707 |
| Loss of Function | 6.93 | 3 | 61.8 | 0.0486 | 0.00000378 | 715 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000683 | 0.0000616 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000367 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. {ECO:0000250, ECO:0000269|PubMed:15084261}.;
- Disease
- DISEASE: Childhood cancer retinoblastoma (RB) [MIM:180200]: Congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated. {ECO:0000269|PubMed:10671068, ECO:0000269|PubMed:11524739, ECO:0000269|PubMed:1352883, ECO:0000269|PubMed:2594029, ECO:0000269|PubMed:7704558, ECO:0000269|PubMed:7795591, ECO:0000269|PubMed:7927327, ECO:0000269|PubMed:8346255, ECO:0000269|PubMed:8605116, ECO:0000269|PubMed:8776589, ECO:0000269|PubMed:9140452, ECO:0000269|PubMed:9311732, ECO:0000269|PubMed:9973307}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bladder cancer (BLC) [MIM:109800]: A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Osteogenic sarcoma (OSRC) [MIM:259500]: A sarcoma originating in bone-forming cells, affecting the ends of long bones. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Non-small cell lung cancer - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Melanoma - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Bladder cancer - Homo sapiens (human);Cell cycle - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Breast cancer - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Cell Cycle;Androgen receptor signaling pathway;miRNA Regulation of DNA Damage Response;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Signaling Pathways in Glioblastoma;Adipogenesis;Spinal Cord Injury;Retinoblastoma (RB) in Cancer;Aryl Hydrocarbon Receptor;Bladder Cancer;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Photodynamic therapy-induced AP-1 survival signaling.;regulation of p27 phosphorylation during cell cycle progression;H19 action Rb-E2F1 signaling and CDK-β-catenin activity;Tumor suppressor activity of SMARCB1;G1 to S cell cycle control;ID signaling pathway;Senescence and Autophagy in Cancer;DNA Damage Response;RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Gene expression (Transcription);Inhibition of replication initiation of damaged DNA by RB1/E2F1;mechanism of gene regulation by peroxisome proliferators via ppara;btg family proteins and cell cycle regulation;telomeres telomerase cellular aging and immortality;cyclin e destruction pathway;human cytomegalovirus and map kinase pathways;influence of ras and rho proteins on g1 to s transition;chaperones modulate interferon signaling pathway;tumor suppressor arf inhibits ribosomal biogenesis;il-2 receptor beta chain in t cell activation;cell cycle: g1/s check point;overview of telomerase rna component gene hterc transcriptional regulation;hiv-1 nef: negative effector of fas and tnf;cyclins and cell cycle regulation;e2f1 destruction pathway;Generic Transcription Pathway;Prolactin;Formation of Senescence-Associated Heterochromatin Foci (SAHF);DNA Damage/Telomere Stress Induced Senescence;Cellular Senescence;Cellular responses to stress;RNA Polymerase II Transcription;Cyclin D associated events in G1;G1 Phase;p73 transcription factor network;Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes;Cyclin E associated events during G1/S transition ;ATF-2 transcription factor network;E2F mediated regulation of DNA replication;Mitotic G1-G1/S phases;Cyclin A:Cdk2-associated events at S phase entry;BCR;fas signaling pathway (cd95);AndrogenReceptor;S Phase;regulation of transcriptional activity by pml;IL1;Cellular responses to external stimuli;p53 signaling pathway;TGF_beta_Receptor;rb tumor suppressor/checkpoint signaling in response to dna damage;Condensation of Prophase Chromosomes;G1/S Transition;Mitotic Prophase;Direct p53 effectors;M Phase;Cell Cycle;IL6;TNFalpha;ID;Cell Cycle, Mitotic;Notch-mediated HES/HEY network;FOXM1 transcription factor network;Regulation of retinoblastoma protein;E2F transcription factor network;Ceramide signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.970
Intolerance Scores
- loftool
- 0.00806
- rvis_EVS
- -0.69
- rvis_percentile_EVS
- 15.12
Haploinsufficiency Scores
- pHI
- 1.00
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.657
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rb1
- Phenotype
- renal/urinary system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; neoplasm; pigmentation phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- rb1
- Affected structure
- retinal ganglion cell
- Phenotype tag
- abnormal
- Phenotype quality
- misrouted
Gene ontology
- Biological process
- G1/S transition of mitotic cell cycle;negative regulation of transcription by RNA polymerase II;regulation of cell growth;tissue homeostasis;aortic valve morphogenesis;chromatin remodeling;regulation of transcription, DNA-templated;negative regulation of protein kinase activity;cell cycle arrest;mitotic cell cycle checkpoint;Ras protein signal transduction;regulation of mitotic cell cycle;negative regulation of gene expression;viral process;cell differentiation;neuron differentiation;androgen receptor signaling pathway;sister chromatid biorientation;neuron projection development;maintenance of mitotic sister chromatid cohesion;glial cell apoptotic process;skeletal muscle cell differentiation;neuron maturation;enucleate erythrocyte differentiation;negative regulation of 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;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;digestive tract development;cell morphogenesis involved in neuron differentiation;negative regulation of epithelial cell proliferation;negative regulation of inflammatory response;striated muscle cell differentiation;cell division;neuron apoptotic process;protein localization to chromosome, centromeric region;cellular response to xenobiotic stimulus;regulation of cohesin loading;negative regulation of transcription involved in G1/S transition of mitotic cell cycle;regulation of centromere complex assembly;hepatocyte apoptotic process;negative regulation of cold-induced thermogenesis;positive regulation of extracellular matrix organization;positive regulation of collagen fibril organization;negative regulation of myofibroblast differentiation;negative regulation of G1/S transition of mitotic cell cycle;positive regulation of transcription regulatory region DNA binding
- Cellular component
- chromatin;nucleus;nucleoplasm;transcription factor complex;spindle;cyclin/CDK positive transcription elongation factor complex;SWI/SNF complex;PML body;Rb-E2F complex
- Molecular function
- proximal promoter sequence-specific DNA binding;RNA polymerase II regulatory region DNA binding;RNA polymerase II activating transcription factor binding;DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;transcription factor binding;kinase binding;ubiquitin protein ligase binding;identical protein binding;androgen receptor binding;phosphoprotein binding;importin-alpha family protein binding;disordered domain specific binding