RB1
Chr 13ADSomaticRB transcriptional corepressor 1
Also known as: OSRC, PPP1R130, RB, p105-Rb, p110-RB1, pRb, pp110
The protein functions as a tumor suppressor that negatively regulates the cell cycle by binding transcription factor E2F1 in its active hypophosphorylated state and stabilizes constitutive heterochromatin to maintain chromatin structure. Mutations cause retinoblastoma and trilateral retinoblastoma through loss of function, inherited in an autosomal dominant pattern with high penetrance. The protein is highly intolerant to loss-of-function variants, consistent with its critical role as a tumor suppressor in childhood cancer.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 43 | 1 | 2 | 0 | 46 |
Likely Pathogenic | 3 | 1 | 2 | 0 | 6 |
VUS | 0 | 127 | 67 | 1 | 195 |
Likely Benign | 0 | 3 | 61 | 48 | 112 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 1 | |||
| Total | 46 | 132 | 134 | 49 | 362 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RB1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer
RECRUITINGHER2 Chimeric Antigen Receptor (CAR) T Cells in Combination With Checkpoint Blockade in Patients With Advanced Sarcoma
RECRUITINGFeasibility of Targeted Bronchial Washing for Molecular Testing by Next Generation Sequencing in Early-stage Lung Cancer
ACTIVE NOT RECRUITINGStudy Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options
ACTIVE NOT RECRUITINGTipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
ACTIVE NOT RECRUITINGSelpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
ACTIVE NOT RECRUITINGGPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma and Metastatic Retinoblastoma
RECRUITINGFertility Preservation in Children With Solid Tumors: Detection of Residual Disease by a Sensitive Method
RECRUITINGGenetically Engineered Cells (FH-FOLR1 ST CAR T Cells) for the Treatment of Advanced Refractory or Recurrent/Progressive Osteosarcoma, FIERCe Trial
RECRUITINGNKG2D.Zeta-NK Cell Conditioning With C7R.GD2.CAR-T Cells for Patients With Relapsed or Refractory Osteosarcoma or Neuroblastoma
NOT YET RECRUITINGThe Relationship Between The Differential Expression Of FosB Protein In Laryngeal Cancer Tissues And Clinical Prognosis
NOT YET RECRUITINGPembrolizumab, Carboplatin and Cabazitaxel in Aggressive Metastatic Castration Resistant Prostate Cancer (PEAPOD_FOS)
RECRUITINGExternal Resources
Links to major genomics databases and tools