RB1 Gene: Retinoblastoma Transcriptional Corepressor 1 - Function, Mutations, and Disease

The RB1 gene encodes the retinoblastoma-associated protein (pRb), a key tumor suppressor that regulates the G1/S cell cycle checkpoint by binding to E2F transcription factors. Loss of RB1 function leads to uncontrolled cell proliferation and is a hallmark of several cancers, including retinoblastoma, osteosarcoma, small cell lung carcinoma, and bladder cancer. Germline mutations in RB1 cause hereditary retinoblastoma, while somatic alterations are frequent in sporadic tumors.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Cell cycle: G1/S transition (Reactome R-HSA-69278)

• p53-independent G1/S DNA damage checkpoint (Reactome R-HSA-69620)

• E2F-mediated regulation of DNA replication (Reactome R-HSA-113501)

• Retinoblastoma gene in cancer (KEGG hsa05200)

• Cellular senescence (KEGG hsa04218)

The retinoblastoma protein (pRb) is a 928-amino-acid nuclear phosphoprotein that acts as a transcriptional corepressor. It contains a pocket domain that binds E2F transcription factors, inhibiting their activity and preventing S-phase entry. pRb is regulated by cyclin-dependent kinase (CDK) phosphorylation; hypophosphorylated pRb is active. Loss of pRb function is central to many cancers, and the gene is a classic example of a tumor suppressor following Knudson's two-hit hypothesis.