Retinoblastoma: genes and variants
Retinoblastoma is linked to 1 analyzed protein (RB1). 33 DNA variants are known to cause it; 1,126 more are uncertain, and 4 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Retinoblastoma
RB1: Retinoblastoma-associated protein
It restrains E2F-dependent transcription and prevents inappropriate G1-to-S cell-cycle progression until proliferative signals are appropriate. Loss of function is a fundamental cancer-driving event, while germline pathogenic variants cause hereditary retinoblastoma and increase risk of additional tumors.
33 disease-causing and 1,122 uncertain variants in RB1 are linked to Retinoblastoma.
Weakly linked (only a few uncertain records): PTCH1 and MAX.
Where Retinoblastoma variants cluster
- RB1 Domain B (positions 640–771): 12 of 33 disease-causing changes, 2.6× more than its size predicts.
Known disease-causing variants in Retinoblastoma
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| RB1 V654L | 654 | Domain B | Disease-causing (★★) |
| RB1 V654M | 654 | Domain B | Disease-causing (★★) |
| RB1 S127T | 127 | Disease-causing (★★) | |
| RB1 G449R | 449 | Domain A | Disease-causing (★★) |
| RB1 S127N | 127 | Disease-causing (★★) | |
| RB1 C706Y | 706 | Domain B | Disease-causing (★★) |
| RB1 S567L | 567 | Domain A | Disease-causing (★★) |
| RB1 S888N | 888 | Domain C | Disease-causing (★★) |
| RB1 R46K | 46 | Disease-causing (★★) | |
| RB1 D286G | 286 | Disease-causing (★★) | |
| RB1 K530R | 530 | Domain A | Disease-causing (★★) |
| RB1 S127I | 127 | Disease-causing (★) | |
| RB1 W195L | 195 | Disease-causing (★) | |
| RB1 L400P | 400 | Domain A | Disease-causing (★) |
| RB1 Q444H | 444 | Domain A | Disease-causing (★) |
| RB1 Q444L | 444 | Domain A | Disease-causing (★) |
| RB1 Q444P | 444 | Domain A | Disease-causing (★) |
| RB1 G449E | 449 | Domain A | Disease-causing (★) |
| RB1 G449V | 449 | Domain A | Disease-causing (★) |
| RB1 L657P | 657 | Domain B | Disease-causing (★) |
| RB1 H483R | 483 | Domain A | Disease-causing (★) |
| RB1 S888T | 888 | Domain C | Disease-causing (★) |
| RB1 M695K | 695 | Domain B | Disease-causing (★) |
| RB1 Q702K | 702 | Domain B | Disease-causing (★) |
| RB1 F760S | 760 | Domain B | Disease-causing (★) |
| RB1 R775S | 775 | Domain C | Disease-causing (★) |
| RB1 L218V | 218 | Disease-causing (★) | |
| RB1 E287D | 287 | Disease-causing (★) | |
| RB1 L662P | 662 | Domain B | Disease-causing (★) |
| RB1 E737D | 737 | Domain B | Disease-causing (★) |
| RB1 K643E | 643 | Domain B | Disease-causing |
| RB1 D701N | 701 | Domain B | Disease-causing |
| RB1 H733Y | 733 | Domain B | Disease-causing |
Uncertain variants in Retinoblastoma that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| RB1 L400V | 400 | Domain A | Conflicting reports (★) | +6: in a 3D region that tolerates change poorly (3R); L400P at the same position is pathogenic; REVEL 0.846 |
| RB1 V654G | 654 | Domain B | Uncertain (★★) | +6: 3 other pathogenic changes within 3 positions; V654L at the same position is pathogenic; REVEL 0.938 |
| RB1 H483L | 483 | Domain A | Uncertain (★) | +6: in a 3D region that tolerates change poorly (3R); H483R at the same position is pathogenic; REVEL 0.959 |
| RB1 V654A | 654 | Domain B | Uncertain (★★) | +6: 3 other pathogenic changes within 3 positions; V654L at the same position is pathogenic; REVEL 0.875 |
Which prediction tools work for Retinoblastoma
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- EVE: 95 out of 100
- PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 90 out of 100
- MutPred2: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 86 out of 100
Diseases related to Retinoblastoma
- Malignant tumor of urinary bladder, also linked to RB1
- Non-small cell lung carcinoma, also linked to RB1
- Lung adenocarcinoma, also linked to RB1
- Hepatocellular carcinoma, also linked to RB1
- Bone osteosarcoma, also linked to RB1
- Hereditary retinoblastoma, also linked to RB1
Frequently asked questions
Which genes are linked to Retinoblastoma?
In CATVariant, Retinoblastoma is linked to 1 analyzed protein: RB1 (Retinoblastoma-associated protein).
How many genetic variants are linked to Retinoblastoma?
1,224 variants: 33 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 1,126 are of uncertain significance or have conflicting reports.
Which uncertain variants in Retinoblastoma look disease-causing?
4 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example RB1 L400V, RB1 V654G, RB1 H483L and RB1 V654A. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Retinoblastoma?
Among tools not trained on clinical labels, EVE separates this disease's known disease-causing variants from harmless ones best (AUROC 0.95, based on 12 disease-causing and 27 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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