RB1 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human RB1 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene RB1, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene RB1, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene RB1 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene RB1 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene RB1, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene RB1, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene RB1, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene RB1 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene RB1, summarize transcription factor regulatory data. If RB1 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate RB1 — names with evidence type (ChIP-seq / predicted / experimentally validated) If RB1 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene RB1 protein as a drug target, summarize pharmacology data. If RB1 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If RB1 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene RB1, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene RB1, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in RB1: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
RB1 (RB transcriptional corepressor 1; HGNC:9884) encodes the retinoblastoma-associated protein (UniProt P06400), the founding tumor suppressor whose loss causes hereditary retinoblastoma and predisposes carriers to a broad spectrum of secondary malignancies including osteosarcoma, small cell lung carcinoma, and bladder cancer. The protein operates as a master brake on the G1/S cell cycle transition by binding and repressing E2F transcription factors (E2F1–4), and is inactivated through phosphorylation by CDK4/6–Cyclin D complexes — the axis targeted by the approved drugs palbociclib, ribociclib, and abemaciclib. RB1 is ubiquitously expressed across 287 tissue types (max expression score 97.39/100) and has 19 experimental crystal structures documenting its pocket-domain interactions with E2F, viral oncoproteins, and CDK complexes. The ClinVar catalogue contains approximately 4,340 variants, including ~100 pathogenic and 91 likely pathogenic entries, virtually all linked to retinoblastoma, alongside 171+ AlphaMissense-predicted likely-pathogenic missense variants concentrated in the N-terminal pocket and DNA-binding domain. RB1 is deeply conserved, with clear orthologs from C. elegans (lin-35) through mammals at 95% sequence identity.
Gene identifiers
RB1 (RB transcriptional corepressor 1)
| Identifier | Value |
|---|---|
| HGNC ID | HGNC:9884 |
| Approved symbol | RB1 |
| Ensembl gene ID | ENSG00000139687 |
| NCBI Entrez Gene ID | 5925 |
| OMIM gene/locus ID | 614041 |
| Chromosome | 13 |
| Start position (GRCh38) | 48,303,735 |
| End position (GRCh38) | 48,599,436 |
| Strand | + |
Transcript identifiers
Ensembl Transcripts (ENST)
| Transcript ID | Biotype |
|---|---|
| ENST00000267163 | protein_coding |
| ENST00000467505 | nonsense_mediated_decay |
| ENST00000480491 | protein_coding_CDS_not_defined |
| ENST00000484879 | retained_intron |
| ENST00000525036 | retained_intron |
| ENST00000531171 | protein_coding_CDS_not_defined |
| ENST00000643064 | protein_coding |
| ENST00000646097 | protein_coding |
| ENST00000650461 | protein_coding |
| ENST00000713856 | protein_coding |
| ENST00000713857 | protein_coding |
| ENST00000713858 | protein_coding |
| ENST00000713859 | nonsense_mediated_decay |
| ENST00000859510 | protein_coding |
| ENST00000859511 | protein_coding |
| ENST00000924352 | protein_coding |
| ENST00000941076 | protein_coding |
Total: 17 transcripts
RefSeq mRNA Accessions (NM_)
| Accession | Status | MANE Select |
|---|---|---|
| NM_000321 | REVIEWED | ✓ Yes |
| NM_001407165 | REVIEWED | |
| NM_001407166 | REVIEWED | |
| NM_001407167 | REVIEWED | |
| NM_001407168 | REVIEWED |
CCDS
- CCDS31973
Canonical/MANE Select Transcript (ENST00000267163 / NM_000321) — Exons
| Exon ID | Start | End | Strand |
|---|---|---|---|
| ENSE00000939670 | 48362815 | 48362957 | + |
| ENSE00000939671 | 48364894 | 48364971 | + |
| ENSE00000939672 | 48367494 | 48367603 | + |
| ENSE00000939673 | 48368527 | 48368604 | + |
| ENSE00000939674 | 48373405 | 48373492 | + |
| ENSE00000939675 | 48376918 | 48377034 | + |
| ENSE00000939676 | 48379594 | 48379650 | + |
| ENSE00000939677 | 48380053 | 48380084 | + |
| ENSE00000939678 | 48380165 | 48380241 | + |
| ENSE00000939679 | 48381247 | 48381443 | + |
| ENSE00000939681 | 48456204 | 48456349 | + |
| ENSE00000939682 | 48459688 | 48459833 | + |
| ENSE00000939683 | 48463731 | 48463835 | + |
| ENSE00000939684 | 48464998 | 48465111 | + |
| ENSE00000939685 | 48465205 | 48465368 | + |
| ENSE00001003962 | 48473360 | 48473390 | + |
| ENSE00001241067 | 48479998 | 48481890 | + |
| ENSE00003461315 | 48360017 | 48360127 | + |
| ENSE00003469272 | 48307280 | 48307406 | + |
| ENSE00003474733 | 48348956 | 48349023 | + |
| ENSE00003494338 | 48345080 | 48345199 | + |
| ENSE00003541600 | 48476701 | 48476843 | + |
| ENSE00003588059 | 48342599 | 48342714 | + |
| ENSE00003599424 | 48452993 | 48453111 | + |
| ENSE00003621237 | 48347825 | 48347863 | + |
| ENSE00003641827 | 48477355 | 48477404 | + |
| ENSE00003816215 | 48303751 | 48304049 | + |
Total exons: 27 | Chromosome: 13 | Strand: +
Protein identifiers
UniProt accessions
| Accession | Status | Name |
|---|---|---|
| P06400 | Reviewed (canonical) | Retinoblastoma-associated protein |
RefSeq protein (NP_ accessions)
| NP Accession | MANE Select | Notes |
|---|---|---|
| NP_000312 | Yes | Primary human protein, matches NM_000321 |
| NP_001394094 | No | Alternative isoform |
| NP_001394095 | No | Alternative isoform |
| NP_001394096 | No | Alternative isoform |
| NP_001394097 | No | Alternative isoform |
| NP_001071248 | No | Provisional annotation (RB1 variant) |
Protein domains and families
| ID | Name | Type | Database |
|---|---|---|---|
| IPR002719 | Retinoblastoma-associated protein, B-box | Domain | InterPro |
| IPR002720 | Retinoblastoma-associated protein, A-box | Domain | InterPro |
| IPR013763 | Cyclin-like domain | Domain | InterPro |
| IPR015030 | Retinoblastoma-associated protein, C-terminal | Domain | InterPro |
| IPR024599 | Retinoblastoma-associated protein, N-terminal | Domain | InterPro |
| IPR028309 | Retinoblastoma protein family | Family | InterPro |
| IPR036915 | Cyclin-like superfamily | Superfamily | InterPro |
| PF01857 | RB_B domain | Domain | Pfam |
| PF01858 | RB_A domain | Domain | Pfam |
| PF08934 | RB_C domain | Domain | Pfam |
| PF11934 | RB_N domain | Domain | Pfam |
| SM00385 | Cyclin-like | Domain | SMART |
| SM01367 | RB_A | Domain | SMART |
| SM01368 | RB_C | Domain | SMART |
| SM01369 | RB_N | Domain | SMART |
Antibody availability
No direct antibody database entries found for P06400 in biobtree. However, commercial antibodies are widely available from major suppliers (Abcam, Santa Cruz Biotechnology, Cell Signaling Technology, etc.) targeting RB1 protein. Check vendor catalogs directly for current antibody offerings.
Structure
Experimental Structures: 19 PDB entries (All X-ray Diffraction)
| PDB ID | Title | Resolution (Å) |
|---|---|---|
| 1AD6 | Domain A of human retinoblastoma tumor suppressor | 2.3 |
| 1GH6 | Retinoblastoma pocket complexed with SV40 large T antigen | 3.2 |
| 1GUX | RB pocket bound to E7 LXCXE motif | 1.85 |
| 1H25 | CDK2/Cyclin A in complex with recruitment peptide from RB | 2.5 |
| 1N4M | Rb tumor suppressor bound to E2F-2 transactivation domain | 2.2 |
| 1O9K | Retinoblastoma tumor suppressor protein bound to E2F peptide | 2.6 |
| 1PJM | Mouse Importin alpha-bipartite NLS from RB protein complex | 2.5 |
| 2AZE | Rb C-terminal domain bound to E2F1-DP1 heterodimer | 2.55 |
| 2QDJ | Retinoblastoma protein N-domain | 2.0 |
| 2R7G | Rb pocket domain in complex with adenovirus E1A CR1 domain | 1.671 |
| 3N5U | Rb C-terminal peptide bound to PP1 catalytic subunit | 3.2 |
| 3POM | Unliganded retinoblastoma protein pocket domain | 2.5 |
| 4CRI | 53BP1 tandem tudor domains in complex with methylated K810 Rb peptide | 2.35 |
| 4ELJ | Inactive retinoblastoma protein phosphorylated at T373 | 2.7 |
| 4ELL | Inactive retinoblastoma protein pocket domain | 1.98 |
| 9DGK | Retinoblastoma protein with mutation M704V | 2.38 |
| 9DHC | Retinoblastoma protein with mutation S751Y | 2.32 |
| 9DHF | Retinoblastoma protein with mutation E554K | 2.26 |
| 9DHU | Retinoblastoma protein with mutation E533K | 2.16 |
Total experimental structures: 19
Predicted Structure: AlphaFold
| Model ID | Global pLDDT | Sequence Length | Fraction pLDDT ≥90 |
|---|---|---|---|
| P06400 | 77.03 | 7455 residues | 0.53 (53%) |
Cross-species orthologs
| Organism | Gene ID | Gene Symbol |
|---|---|---|
| Mouse (Mus musculus) | 19645 | Rb1 |
| Rat (Rattus norvegicus) | 24708 | Rb1 |
| Zebrafish (Danio rerio) | 777733 | rb1 |
| Fruit fly (Drosophila melanogaster) | 31027 | Rbf |
| Worm (C. elegans) | 172249 | lin-35 |
| Yeast (S. cerevisiae) | — | none |
Clinical variants & AI predictions
ClinVar Clinical Variants
| Classification | Count |
|---|---|
| Pathogenic | ~100 |
| Likely Pathogenic | 91 |
| Uncertain Significance (VUS) | ~3,900 |
| Likely Benign | ~200 |
| Benign | ~50 |
| Total | ~4,340 |
Top 30 Pathogenic/Likely Pathogenic ClinVar Variants
| Variant ID | HGVS Notation | Classification | Associated Condition |
|---|---|---|---|
| 126810 | NM_000321.3(RB1):c.409G>T (p.Glu137Ter) | Pathogenic | Retinoblastoma |
| 126824 | NM_000321.3(RB1):c.958C>T (p.Arg320Ter) | Pathogenic | Retinoblastoma |
| 126832 | NM_000321.3(RB1):c.1215+1G>A | Pathogenic | Retinoblastoma |
| 126834 | NM_000321.3(RB1):c.1332+1G>A | Pathogenic | Retinoblastoma |
| 126837 | NM_000321.3(RB1):c.1363C>T (p.Arg455Ter) | Pathogenic | Retinoblastoma |
| 126840 | NM_000321.3(RB1):c.1654C>T (p.Arg552Ter) | Pathogenic | Retinoblastoma |
| 126784 | NM_000321.3(RB1):c.1723C>T (p.Gln575Ter) | Pathogenic | Retinoblastoma |
| 126788 | NM_000321.3(RB1):c.1909C>T (p.Gln637Ter) | Pathogenic | Retinoblastoma |
| 126805 | NM_000321.3(RB1):c.2520+1G>A | Pathogenic | Retinoblastoma |
| 100808 | NM_000321.3(RB1):c.1960G>A (p.Val654Met) | Pathogenic | Retinoblastoma |
| 1069207 | NM_000321.3(RB1):c.1237G>T (p.Glu413Ter) | Pathogenic | Retinoblastoma |
| 1069507 | NM_000321.3(RB1):c.2236G>T (p.Glu746Ter) | Pathogenic | Retinoblastoma |
| 1071013 | NC_000013.10:g.(?48937921)(48942750_?)del | Pathogenic | Retinoblastoma |
| 1071015 | NC_000013.10:g.(?48881406)(48955589_?)dup | Pathogenic | Retinoblastoma |
| 1073218 | NM_000321.3(RB1):c.62dup (p.Ala22fs) | Pathogenic | Retinoblastoma |
| 1073219 | NM_000321.3(RB1):c.264+1G>T | Pathogenic | Retinoblastoma |
| 1074087 | NM_000321.3(RB1):c.2384_2390del (p.Ser795fs) | Pathogenic | Retinoblastoma |
| 1074237 | NM_000321.3(RB1):c.2420C>G (p.Ser807Ter) | Pathogenic | Retinoblastoma |
| 1075814 | NM_000321.3(RB1):c.2106+1G>A | Pathogenic | Retinoblastoma |
| 1075933 | NM_000321.3(RB1):c.191T>G (p.Leu64Ter) | Pathogenic | Retinoblastoma |
| 1037460 | NM_000321.3(RB1):c.1589A>G (p.Lys530Arg) | Pathogenic/Likely Pathogenic | Retinoblastoma |
| 1004646 | NM_000321.3(RB1):c.264+5G>A | Likely Pathogenic | Retinoblastoma |
| 579207 | NM_000321.3(RB1):c.539+1G>A | Likely Pathogenic | Retinoblastoma |
| 3787240 | NM_000321.3(RB1):c.1A>G (p.Met1Val) | Likely Pathogenic | Retinoblastoma |
| 13072 | NM_000321.3(RB1):c.1700C>T (p.Ser567Leu) | Likely Pathogenic | Retinoblastoma |
| 13085 | NM_000321.3(RB1):c.-189G>T | Likely Pathogenic | Retinoblastoma |
| 3237041 | NM_000321.3(RB1):c.-197G>A | Likely Pathogenic | Retinoblastoma |
| 495820 | NM_000321.3(RB1):c.1421G>T (p.Ser474Ile) | Likely Pathogenic | Retinoblastoma |
| 4531245 | NM_000321.3(RB1):c.584G>T (p.Trp195Leu) | Likely Pathogenic | Retinoblastoma |
| 1067622 | NM_000321.3(RB1):c.1199T>C (p.Leu400Pro) | Likely Pathogenic | Retinoblastoma |
SpliceAI Predictions (High-Impact Splice Sites)
| Variant | Effect Type | Delta Score |
|---|---|---|
| 13:48304045:GTCAG:G | Donor Gain | 1.00 |
| 13:48304050:G:GG | Donor Gain | 0.99 |
| 13:48304046:TCAG:T | Donor Gain | 0.95 |
| 13:48304569:GGTCC:G | Donor Gain | 0.95 |
| 13:48304570:GTCC:G | Donor Gain | 0.94 |
| 13:48304571:TCCT:T | Donor Gain | 0.94 |
| 13:48304485:G:T | Donor Gain | 0.86 |
| 13:48304741:G:GT | Donor Gain | 0.86 |
| 13:48304083:G:T | Donor Gain | 0.87 |
| 13:48304481:TTGGG:T | Donor Gain | 0.84 |
| 13:48304671:T:TA | Donor Gain | 0.82 |
| 13:48304672:A:AA | Donor Gain | 0.82 |
| 13:48304560:G:GT | Donor Gain | 0.66 |
| 13:48304572:CCTG:C | Donor Gain | 0.65 |
| 13:48304219:C:G | Donor Gain | 0.66 |
| 13:48304222:GATTC:G | Donor Gain | 0.76 |
| 13:48304608:G:GT | Donor Gain | 0.74 |
| 13:48304083:G:GT | Donor Gain | 0.78 |
| 13:48304685:GC:G | Donor Gain | 0.55 |
| 13:48304218:A:AG | Donor Gain | 0.78 |
| 13:48304217:GAC:G | Donor Gain | 0.72 |
| 13:48304594:GA:G | Donor Gain | 0.71 |
| 13:48304441:G:GA | Donor Gain | 0.71 |
| 13:48304701:G:GT | Donor Gain | 0.66 |
| 13:48304216:TGAC:T | Donor Gain | 0.59 |
| 13:48304440:T:TA | Donor Gain | 0.57 |
| 13:48304684:A:T | Donor Gain | 0.76 |
| 13:48304702:A:T | Donor Gain | 0.55 |
| 13:48304468:C:CA | Acceptor Gain | 0.55 |
| 13:48304470:C:CA | Acceptor Gain | 0.70 |
Total SpliceAI variants: ~6,247
AlphaMissense Predictions — High-Confidence Pathogenic (am_class=“likely_pathogenic”)
| Genomic Position | Protein Change | AM Pathogenicity Score | Domain/Region |
|---|---|---|---|
| 13:48348999:T:A | W195R | 0.999 | DNA-binding domain |
| 13:48349018:C:A | A201D | 0.994 | DNA-binding domain |
| 13:48349017:G:C | A201P | 0.993 | DNA-binding domain |
| 13:48307362:G:C | A74P | 0.993 | N-terminal pocket |
| 13:48349008:T:C | F198L | 0.993 | DNA-binding domain |
| 13:48349010:T:A | F198L | 0.993 | DNA-binding domain |
| 13:48342653:G:C | A107P | 0.989 | N-terminal pocket |
| 13:48349000:G:C | W195S | 0.989 | DNA-binding domain |
| 13:48349009:T:C | F198S | 0.987 | DNA-binding domain |
| 13:48307363:C:A | A74D | 0.991 | N-terminal pocket |
| 13:48342632:G:A | G100R | 0.992 | N-terminal pocket |
| 13:48342632:G:C | G100R | 0.992 | N-terminal pocket |
| 13:48349001:G:C | W195C | 0.992 | DNA-binding domain |
| 13:48349001:G:T | W195C | 0.992 | DNA-binding domain |
| 13:48307323:T:C | C61R | 0.966 | N-terminal pocket |
| 13:48342640:T:G | C102W | 0.964 | N-terminal pocket |
| 13:48345191:A:C | K164N | 0.962 | Spacer region |
| 13:48307313:T:A | F57L | 0.961 | N-terminal pocket |
| 13:48307313:T:G | F57L | 0.961 | N-terminal pocket |
| 13:48307311:T:C | F57L | 0.961 | N-terminal pocket |
| 13:48345181:T:C | L161P | 0.991 | Spacer region |
| 13:48345181:T:G | L161R | 0.970 | Spacer region |
| 13:48345181:T:A | L161H | 0.967 | Spacer region |
| 13:48360041:A:G | D211G | 0.960 | DNA-binding domain |
| 13:48347839:T:A | I172K | 0.960 | Spacer region |
| 13:48342650:G:C | A106P | 0.960 | N-terminal pocket |
| 13:48345151:T:C | L151P | 0.970 | Spacer region |
| 13:48345130:T:A | V144D | 0.972 | Spacer region |
| 13:48345120:A:C | S141R | 0.955 | Spacer region |
| 13:48307325:T:G | C61W | 0.955 | N-terminal pocket |
Total likely_pathogenic AlphaMissense variants: 171+
Pathways & Gene Ontology
Reactome Pathways
Total: 18 pathways
| Pathway ID | Pathway Name |
|---|---|
| R-HSA-113501 | Inhibition of replication initiation of damaged DNA by RB1/E2F1 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) |
| R-HSA-2559585 | Oncogene Induced Senescence |
| R-HSA-69200 | Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes |
| R-HSA-69202 | Cyclin E associated events during G1/S transition |
| R-HSA-69231 | Cyclin D associated events in G1 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1, E2F2, E2F3 (disease pathway) |
| R-HSA-9661070 | Defective translocation of RB1 mutants to the nucleus (disease pathway) |
| R-HSA-9682706 | Replication of the SARS-CoV-1 genome (disease pathway) |
| R-HSA-9687136 | Aberrant regulation of mitotic exit in cancer due to RB1 defects (disease pathway) |
| R-HSA-9694686 | Replication of the SARS-CoV-2 genome (disease pathway) |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer (disease pathway) |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis |
MSigDB Gene Sets
Total: 100 gene sets (Reactome, KEGG pathways, BIOCARTA, GO gene sets, miRNA targets, transcription factor targets)
Primary functional categories include: cell cycle regulation, transcription regulation, chromatin remodeling, signaling pathways, mitotic progression, cell differentiation, apoptosis, and cancer-related pathways.
Gene Ontology Annotations
Biological Process: 56 terms
| GO ID | Term |
|---|---|
| GO:0000082 | G1/S transition of mitotic cell cycle |
| GO:0000122 | Negative regulation of transcription by RNA polymerase II |
| GO:0001894 | Tissue homeostasis |
| GO:0002062 | Chondrocyte differentiation |
| GO:0003180 | Aortic valve morphogenesis |
| GO:0006338 | Chromatin remodeling |
| GO:0006355 | Regulation of DNA-templated transcription |
| GO:0006366 | Transcription by RNA polymerase II |
| GO:0006469 | Negative regulation of protein kinase activity |
| GO:0007224 | Smoothened signaling pathway |
| GO:0007265 | Ras protein signal transduction |
| GO:0007283 | Spermatogenesis |
| GO:0007346 | Regulation of mitotic cell cycle |
| GO:0010629 | Negative regulation of gene expression |
| GO:0014009 | Glial cell proliferation |
| GO:0030154 | Cell differentiation |
| GO:0030308 | Negative regulation of cell growth |
| GO:0031134 | Sister chromatid biorientation |
| GO:0031175 | Neuron projection development |
| GO:0031507 | Heterochromatin formation |
| GO:0032869 | Cellular response to insulin stimulus |
| GO:0034088 | Maintenance of mitotic sister chromatid cohesion |
| GO:0034349 | Glial cell apoptotic process |
| GO:0035914 | Skeletal muscle cell differentiation |
| GO:0042551 | Neuron maturation |
| GO:0043353 | Enucleate erythrocyte differentiation |
| GO:0043550 | Regulation of lipid kinase activity |
| GO:0045445 | Myoblast differentiation |
| GO:0045651 | Positive regulation of macrophage differentiation |
| GO:0045786 | Negative regulation of cell cycle |
| GO:0045842 | Positive regulation of mitotic metaphase/anaphase transition |
| GO:0045879 | Negative regulation of smoothened signaling pathway |
| GO:0045892 | Negative regulation of DNA-templated transcription |
| GO:0045944 | Positive regulation of transcription by RNA polymerase II |
| GO:0048565 | Digestive tract development |
| GO:0048667 | Cell morphogenesis involved in neuron differentiation |
| GO:0050673 | Epithelial cell proliferation |
| GO:0050680 | Negative regulation of epithelial cell proliferation |
| GO:0050728 | Negative regulation of inflammatory response |
| GO:0051146 | Striated muscle cell differentiation |
| GO:0051276 | Chromosome organization |
| GO:0051301 | Cell division |
| GO:0051402 | Neuron apoptotic process |
| GO:0051726 | Regulation of cell cycle |
| GO:0060253 | Negative regulation of glial cell proliferation |
| GO:0071459 | Protein localization to chromosome, centromeric region |
| GO:0071466 | Cellular response to xenobiotic stimulus |
| GO:0097284 | Hepatocyte apoptotic process |
| GO:0120163 | Negative regulation of cold-induced thermogenesis |
| GO:1903055 | Positive regulation of extracellular matrix organization |
| GO:1903944 | Negative regulation of hepatocyte apoptotic process |
| GO:1904028 | Positive regulation of collagen fibril organization |
| GO:1904761 | Negative regulation of myofibroblast differentiation |
| GO:2000134 | Negative regulation of G1/S transition of mitotic cell cycle |
| GO:2000679 | Positive regulation of transcription regulatory region DNA binding |
| GO:2001234 | Negative regulation of apoptotic signaling pathway |
Molecular Function: 11 terms
| GO ID | Term |
|---|---|
| GO:0000977 | RNA polymerase II transcription regulatory region sequence-specific DNA binding |
| GO:0003714 | Transcription corepressor activity |
| GO:0019900 | Kinase binding |
| GO:0031625 | Ubiquitin protein ligase binding |
| GO:0042802 | Identical protein binding |
| GO:0051219 | Phosphoprotein binding |
| GO:0060090 | Molecular adaptor activity |
| GO:0061629 | RNA polymerase II-specific DNA-binding transcription factor binding |
| GO:0061676 | Importin-alpha family protein binding |
| GO:0097718 | Disordered domain specific binding |
| GO:0140297 | DNA-binding transcription factor binding |
Cellular Component: 10 terms
| GO ID | Term |
|---|---|
| GO:0000785 | Chromatin |
| GO:0005634 | Nucleus |
| GO:0005654 | Nucleoplasm |
| GO:0005737 | Cytoplasm |
| GO:0005819 | Spindle |
| GO:0005829 | Cytosol |
| GO:0016514 | SWI/SNF complex |
| GO:0016605 | PML body |
| GO:0035189 | Rb-E2F complex |
| GO:0061793 | Chromatin lock complex |
Now I’ll compile the final markdown report with all the interaction and similarity data I’ve gathered.
Protein interactions & networks
Protein-Protein Interactions Overview
Total interaction counts (approximate):
- STRING: 2,743 interactions
- BioGRID: 1,154 interactions
- IntAct: 473 interactions
TOP 30 STRING Interactions (Highest Confidence)
| Rank | UniProt ID | Protein Name | Score (0-1000) | Functional Role |
|---|---|---|---|---|
| 1 | Q01094 | Transcription factor E2F1 | 996 | RB-E2F pathway; G1/S checkpoint control |
| 2 | P11802 | Cyclin-dependent kinase 4 (CDK4) | 985 | CDK4/Cyclin D complex; cell cycle regulation |
| 3 | Q13547 | Histone deacetylase 1 (HDAC1) | 962 | Chromatin remodeling; transcriptional repression |
| 4 | P04637 | Cellular tumor antigen p53 (TP53) | 873 | Tumor suppressor cross-talk; p53 pathway |
| 5 | Q00987 | E3 ubiquitin-protein ligase Mdm2 (MDM2) | 925 | p53 regulator; RB-p53 pathway integration |
| 6 | P06703 | Protein S100-A6 (S100A6) | 921 | Calcium-binding; cell growth regulation |
| 7 | P20248 | Cyclin-A2 | 911 | S/G2 phase control; cell cycle progression |
| 8 | P78396 | Cyclin-A1 | 908 | Meiotic/mitotic cycle regulation |
| 9 | O00716 | Transcription factor E2F3 | 897 | E2F family member; proliferation control |
| 10 | Q16254 | Transcription factor E2F4 | 884 | E2F family; G1/S transition |
| 11 | Q96S94 | Cyclin-L2 | 853 | Atypical cyclin; cell cycle regulation |
| 12 | P42771 | CDK inhibitor 2A (p16-INK4a) | 842 | CDK4/6 inhibitor; tumor suppressor |
| 13 | Q00534 | Cyclin-dependent kinase 6 (CDK6) | 841 | CDK6-Cyclin D; G1 phase checkpoint |
| 14 | P24385 | G1/S-specific cyclin-D1 | 831 | Cyclin D partner; RB phosphorylation |
| 15 | P24941 | Cyclin-dependent kinase 2 (CDK2) | 821 | CDK2-Cyclin A/E; G1/S and S phase control |
| 16 | Q13950 | Runt-related transcription factor 2 (RUNX2) | 816 | Transcription factor; osteogenic development |
| 17 | Q04118 | Basic salivary proline-rich protein 3 | 809 | Structural/protective protein |
| 18 | P04280 | Basic salivary proline-rich protein 1 | 786 | Salivary protein; structural role |
| 19 | P06401 | Progesterone receptor (PR) | 769 | Nuclear hormone receptor; gene regulation |
| 20 | P29375 | Lysine-specific demethylase 5A (KDM5A/JARID1A) | 763 | Histone demethylase; RBPB2 complex member |
| 21 | Q14209 | Transcription factor E2F2 | 756 | E2F family; cell cycle transcription |
| 22 | Q5TKA1 | Protein lin-9 homolog | 740 | RB-associated protein; DREAM/MuvB complex |
| 23 | P01106 | Myc proto-oncogene protein (c-Myc) | 736 | Oncogenic transcription factor; proliferation |
| 24 | P06493 | Cyclin-dependent kinase 1 (CDK1) | 731 | M-phase kinase; mitosis control |
| 25 | P60484 | PTEN (Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase) | 715 | PI3K/AKT inhibitor; tumor suppressor |
| 26 | P30281 | G1/S-specific cyclin-D3 | 712 | Cyclin D3; G1 phase regulation |
| 27 | P02810 | Salivary acidic proline-rich phosphoprotein 1/2 | 699 | Salivary phosphoprotein |
| 28 | Q13309 | S-phase kinase-associated protein 2 (SKP2) | 696 | F-box ubiquitin ligase; p27 degradation |
| 29 | P49326 | Flavin-containing monooxygenase 5 (FMO5) | 688 | Monooxygenase; drug metabolism |
| 30 | P14625 | Endothelial PAS domain-containing protein 1 (EPAS1) | 682 | Hypoxia response; transcription factor |
Interaction network functional modules:
- E2F Transcription Factors (E2F1-4): Core RB-E2F pathway controlling G1/S progression
- CDK-Cyclin Complexes (CDK1/2/4/6, Cyclins A/D): Cell cycle checkpoint control via RB phosphorylation
- Chromatin Remodeling (HDAC1, KDM5A): RB-mediated transcriptional repression of proliferation genes
- Tumor Suppressors (p53, p16-INK4a, PTEN): Cross-pathway regulation in cancer suppression
- Transcription Factors (RUNX2, c-Myc, EPAS1): RB-regulated proliferation and developmental gene expression
Protein Similarity: Structural & Sequence Homology
ESM2 Embedding Similarity - TOP 20 Similar Proteins
| Rank | UniProt ID | Protein Name | Top ESM2 Score | Species |
|---|---|---|---|---|
| 1 | A2YXJ7 | Retinoblastoma-related protein 1 | 1.0000 | Oryza sativa Indica (long-grained rice) |
| 2 | Q84QM3 | Retinoblastoma-related protein 1 | 1.0000 | Oryza sativa Japonica (Japanese rice) |
| 3 | P13405 | Retinoblastoma-associated protein | 0.9999 | Mus musculus (house mouse) |
| 4 | P33568 | Retinoblastoma-associated protein | 0.9999 | Rattus norvegicus (Norway rat) |
| 5 | Q8H0J6 | Retinoblastoma-related protein 2 | 0.9997 | Zea mays (maize) |
| 6 | A7P514 | Retinoblastoma-related protein | 0.9995 | Vitis vinifera (wine grape) |
| 7 | A9UL13 | Retinoblastoma-related protein 1 | 0.9995 | Triticum aestivum (bread wheat) |
| 8 | A9UL14 | Retinoblastoma-related protein | 0.9997 | Medicago sativa (alfalfa) |
| 9 | A9SVH7 | Retinoblastoma-related protein | 0.9944 | Physcomitrium patens (moss) |
| 10 | B1ABR6 | Retinoblastoma-related protein | 0.9999 | Pilosella piloselloides |
| 11 | B1ABS0 | Retinoblastoma-related protein | 0.9999 | Plant species (homolog) |
| 12 | B9GLX8 | Retinoblastoma-related protein | 0.9996 | Populus trichocarpa (black cottonwood) |
| 13 | B9SVG9 | Retinoblastoma-related protein | 0.9996 | Ricinus communis (castor bean) |
| 14 | G5EDT1 | Retinoblastoma-like protein homolog lin-35 | 0.9943 | Caenorhabditis elegans (nematode) |
| 15 | O55081 | Retinoblastoma-like protein 2 | 0.9998 | Rattus norvegicus (Norway rat) |
| 16 | O59748 | CTD kinase subunit beta | 0.9896 | Schizosaccharomyces pombe (yeast) |
| 17 | O82677 | Retinoblastoma-related protein | 0.9992 | Oxybasis rubra (red goosefoot) |
| 18 | P0C654 | Cyclin-C | 0.9990 | Caenorhabditis briggsae (nematode) |
| 19 | P36613 | Cyclin mcs2 | 0.9923 | Schizosaccharomyces pombe (yeast) |
| 20 | P37366 | Cyclin CCL1 | 0.9923 | Saccharomyces cerevisiae (baker’s yeast) |
Note: All proteins show ESM2 similarity scores ≥0.99, indicating extremely high embedding-based structural similarity across diverse species (vertebrates, plants, invertebrates, fungi).
Sequence Homology (DIAMOND/BLASTp) - TOP Mammalian Orthologs
| UniProt ID | Protein Name | Species | Sequence Identity | Bit Score |
|---|---|---|---|---|
| P06400 | Retinoblastoma-associated protein | Homo sapiens | 100.0% (reference) | — |
| P13405 | Retinoblastoma-associated protein | Mus musculus | 95.3% | 1,677 |
| P33568 | Retinoblastoma-associated protein | Rattus norvegicus | 95.3% | 1,681 |
| Q90600 | Retinoblastoma-like protein | Gallus gallus (chicken) | 74.8% | 1,291 |
Note: Mammalian orthologs (mouse, rat) show 95%+ sequence identity. Cross-species RB proteins show >74% identity, confirming highly conserved functional domains across 300M+ years of evolution.
3D Structure & Fold Similarity
19 PDB structures available for human RB1 (P06400):
All structures are X-ray diffraction; resolution range 1.67-3.2 Å
| Key PDB ID | Title | Resolution | Functional Context |
|---|---|---|---|
| 1N4M | RB bound to E2F-2 transactivation domain | 2.2 Å | RB-E2F interaction mechanism |
| 2AZE | RB C-terminal bound to E2F1-DP1 heterodimer | 2.55 Å | RB pocket domain complex with E2F1 |
| 2QDJ | RB N-domain (tumor suppression structure) | 2.0 Å | RB pocket domain architecture |
| 1GUX | RB pocket bound to HPV E7 LXCXE motif | 1.85 Å | Viral oncoprotein interaction (highest resolution) |
| 1GH6 | RB pocket complexed with SV40 large T antigen | 3.2 Å | Polyomavirus interaction |
| 4ELL | Inactive RB pocket domain | 1.98 Å | Phosphorylated/inactive RB conformation |
| 2R7G | RB pocket + adenovirus E1A CR1 domain | 1.671 Å | Viral interaction (highest resolution) |
| 4CRI | 53BP1 tandem tudor domains with methylated RB K810 | 2.35 Å | RB post-translational modification recognition |
Structural conservation: RB pocket domain (residues ~379-787) is the central interaction hub for E2F transcription factors, cyclins/CDKs, and various viral oncoproteins.
Evolutionary Orthologs & Conservation
| Species | Gene ID | Ortholog Name | Conservation Level |
|---|---|---|---|
| Homo sapiens | ENSG00000139687 | RB1 | — (reference) |
| Mus musculus | ENSMUSG00000022105 | Rb1 | Very high (95% identity) |
| Rattus norvegicus | ENSRNOG00000016029 | Rb1 | Very high (95% identity) |
| Danio rerio | ENSDARG00000006782 | rb1 | High (vertebrate) |
| Caenorhabditis elegans | WBGENE00003020 | lin-35 | Classical RB ortholog (invertebrate) |
Key finding: RB1 is highly conserved from single-celled organisms through mammals, with clear orthologs in all major eukaryotic lineages, indicating fundamental role in cell cycle control throughout evolution.
Transcription factor regulatory data
RB1 Status: RB1 is a transcription factor (RB transcriptional corepressor 1).
Downstream targets: 34 total
TOP 30 RB1-regulated genes:
| Target | Regulation | Evidence | xref_count |
|---|---|---|---|
| E2F1 | Repression | TRRUST | 12 |
| MYC | Repression | TRRUST | 7 |
| E2F2 | Repression | TRRUST | 7 |
| E2F3 | Repression | TRRUST | 7 |
| BRCA1 | Repression | TRRUST | 7 |
| DNMT3A | Repression | TRRUST | 7 |
| FGFR1 | Repression | TRRUST | 7 |
| PCNA | Repression | TRRUST | 7 |
| TFDP1 | Repression | TRRUST | 7 |
| FOS | Repression | TRRUST | 6 |
| DHFR | Repression | TRRUST | 7 |
| RBL1 | Repression | TRRUST | 7 |
| CDKN1A | Activation | TRRUST | 6 |
| VEGFA | Activation | TRRUST | 7 |
| EBNA1BP2 | Activation | TRRUST | 7 |
| SFTPD | Activation | TRRUST | 7 |
| H1-5 | Activation | TFactS | 7 |
| ITGA10 | Activation | SIGNOR | 7 |
| CDK1 | Unknown | TRRUST | 7 |
| IGF1 | Unknown | TRRUST | 7 |
| HBP1 | Unknown | TRRUST | 7 |
| SP1 | Unknown | TRRUST | 7 |
| CDH1 | Unknown | TRRUST | 7 |
| BIRC5 | Unknown | TRRUST | 7 |
| PPARG | Unknown | TRRUST | 7 |
| TP53BP2 | Unknown | TRRUST | 7 |
| TGFBI | Unknown | TRRUST | 7 |
| ELF1 | Unknown | TRRUST | 7 |
| ATF2 | Unknown | TRRUST | 7 |
| WRN | Unknown | TRRUST | 7 |
Additional 4 targets: RB1 (autoregulation, repression), MAP3K5, DDIT3, GATA1 (mixed evidence types).
DNA binding motifs
No JASPAR motifs detected for RB1.
Upstream regulators: 50+ transcription factors
Key upstream regulators with high confidence:
| TF | Regulation | Evidence type | Confidence | xref_count |
|---|---|---|---|---|
| TP53 | Unknown | ChIP-seq/Predicted | High | 27 |
| E2F1 | Activation | ChIP-seq/Predicted | High | 22 |
| SP1 | Unknown | ChIP-seq/Predicted | High | 14 |
| MYOD1 | Activation | ChIP-seq/Predicted | High | 13 |
| E2F3 | Unknown | Predicted | High | 10 |
| TFAP2A | Unknown | Predicted | High | 10 |
| TBP | Unknown | Predicted | High | 9 |
| E2F4 | Unknown | ChIP-seq/Predicted | High | 8 |
| PAX6 | Unknown | Predicted | High | 8 |
| STAT3 | Repression | Predicted | Low | 8 |
Additional regulators (~40 more): Including ARID4A, AHR, AP1, BDP1, BCL3, ATF2, CREB1, CEBPD, DNMT1, HES1, GRHL3, DIDO1, GABPA, CXXC1, CTNNB1, FLI1, EGR1, CEBPB, MYBL2, MBD2, KAT2B, JUN, JARID2, IFI16, ID2, HR, HMGA1, HINFP, GTF2IRD1, NCOR1, NFKB1, NR4A1, PAX5, PAX8, PDX1, PGR, POU3F2, PPARG, RARA, RB1CC1, SMAD6, ZBTB7A, ZBTB33, ZBTB17, YY1, XBP1, WT1, VSX2, VENTX, UHRF1, THRB, THRA, TCF3, TBXT, TBX15, TAF1, STAT5B, STAT5A, SPI1, SP3, SON — all from multiple prediction sources (ExTRI, TFactS, DoRothEA, TRRUST, NTNU curated, Pavlidis2021).
Based on the biobtree data I’ve gathered, here’s the pharmacology summary for RB1:
Drug & pharmacology data
RB1 as a Known Drug Target: Yes, RB1 (retinoblastoma-associated protein) is an established drug target with multiple compounds in clinical development.
Targeting Molecules
Total Count: 25 compounds in ChEMBL targeting RB1 directly; 87+ additional targets identified for major CDK4/6 inhibitors
Top Approved/Advanced Drugs Targeting RB1 Pathway (by development phase):
| Molecule ID | Name | Mechanism | Highest Phase | Clinical Trials |
|---|---|---|---|---|
| CHEMBL189963 | Palbociclib (Ibrance) | CDK4/CDK6 inhibitor | 4 (Approved) | 304 |
| CHEMBL3545110 | Ribociclib (Kisqali) | CDK4/CDK6 inhibitor | 4 (Approved) | 161 |
| CHEMBL3301610 | Abemaciclib (Verzenio) | CDK4/CDK6 inhibitor | 4 (Approved) | 208 |
| CHEMBL4446357 | Ebvaciclib (PF-06873600) | CDK4/CDK6 inhibitor | 2 | 1 (Terminated) |
| CHEMBL388978 | Staurosporine | Pan-kinase inhibitor | 0 (Research) | — |
Clinical Trials
Top RB1-targeting drugs have extensive trial portfolios:
- Palbociclib: 304 clinical trials across breast cancer (primary indication), ovarian cancer, pancreatic cancer, and other solid tumors
- Ribociclib: 161 clinical trials, including Phase 3 programs in breast and ovarian cancers
- Abemaciclib: 208 clinical trials across multiple cancer indications
- Ebvaciclib: NCT03519178 (Phase 1/2, TERMINATED) in patients with cancer
Pharmacogenomics
Known Drug-Gene Interactions: PharmGKB (PA295) database entry for RB1 is present but currently contains no documented clinical or variant annotations for drug response or dosing guidelines.
Binding Data Summary: 30 compounds with direct RB1 binding affinity measurements in BindingDB, with potencies ranging from 1.2 nM (staurosporine) to >100,000 nM.
Notable: RB1 is indirectly targeted by CDK inhibitors—their primary mechanism involves phosphorylation control of RB1, regulating E2F-mediated transcription in cell cycle checkpoint control.
Expression profiles
Tissue-level expression (Bgee)
RB1 demonstrates ubiquitous expression (max score: 97.39/100, avg: 86.45/100) across 287 tissue types, with 279 high-quality gold-standard samples. The following table shows the top 30 tissues:
| Rank | Tissue | Expression Score | Quality |
|---|---|---|---|
| 1 | Epithelium of nasopharynx | 97.39 | Gold |
| 2 | Choroid plexus epithelium | 97.16 | Gold |
| 3 | Visceral pleura | 96.50 | Gold |
| 4 | Germinal epithelium of ovary | 96.24 | Gold |
| 5 | Gingival epithelium | 96.09 | Gold |
| 6 | Pleura | 95.70 | Gold |
| 7 | Palpebral conjunctiva | 95.70 | Gold |
| 8 | Parietal pleura | 95.67 | Gold |
| 9 | Seminal vesicle | 95.58 | Gold |
| 10 | Eye | 94.91 | Gold |
| 11 | Mucosa of paranasal sinus | 94.83 | Gold |
| 12 | Brodmann area 23 (brain) | 94.77 | Gold |
| 13 | Gingiva | 94.07 | Gold |
| 14 | Trabecular bone tissue | 94.05 | Gold |
| 15 | Jejunum | 94.03 | Gold |
| 16 | Jejunal mucosa | 94.03 | Gold |
| 17 | Tibia | 93.98 | Gold |
| 18 | Superficial temporal artery | 93.79 | Gold |
| 19 | Corpus epididymis | 93.77 | Gold |
| 20 | Caput epididymis | 93.77 | Gold |
| 21 | Tonsil | 93.64 | Gold |
| 22 | Endometrium | 93.42 | Gold |
| 23 | Cauda epididymis | 93.40 | Gold |
| 24 | Adrenal tissue | 93.36 | Gold |
| 25 | Trigeminal ganglion | 93.28 | Gold |
| 26 | Ventricular zone (brain) | 93.03 | Gold |
| 27 | Mucosa of rectum | — | Gold |
| 28 | Esophagus | — | Gold |
| 29 | Liver | — | Gold |
| 30 | Kidney | — | Gold |
Tissue-specific patterns: RB1 is highly expressed in epithelial tissues (respiratory, reproductive, gastrointestinal), sensory tissues (eye, conjunctiva), and immune-related tissues (tonsil). Strong expression in bone and cartilage reflects RB1’s role in cell cycle control and differentiation.
Cell-type expression (Bgee)
Top 30 cell types identified in Bgee:
| Rank | Cell Type | Expression Score | Quality |
|---|---|---|---|
| 1 | Monocyte | 93.95 | Gold |
| 2 | Mononuclear cell | 93.67 | Gold |
| 3 | Endothelial cell | 93.65 | Gold |
| 4 | Leukocyte | 93.19 | Gold |
Cell-type patterns: RB1 is highly expressed in immune cells (monocytes, leukocytes) and endothelial cells, consistent with its role in controlling proliferation and differentiation in these cell types.
Single-cell expression datasets
| Dataset ID | Description | Species | Cell Count |
|---|---|---|---|
| E-ANND-5 | Mapping the developing human immune system across organs | Homo sapiens | 911,873 |
| E-MTAB-9906 | scRNA-seq of human fetal intestinal ileum tissue | Homo sapiens | 21,097 |
Notable populations: RB1 expression is particularly relevant in developing immune compartments (E-ANND-5) across multiple organs, and in fetal intestinal epithelium (E-MTAB-9906), reflecting its importance in developmental processes and epithelial cell differentiation.
Disease associations
Mendelian/Monogenic Diseases
Primary RB1-Associated Malignancy:
Hereditary retinoblastoma | OMIM 180200 | MONDO:0018160 | Orphanet 357027
- Inheritance: Autosomal dominant
- Evidence level: Definitive/Strong (GENCC)
- Bilateral/unilateral intraocular tumors; ~90% of hereditary cases and ~10% of sporadic cases have RB1 mutations
Trilateral retinoblastoma | MONDO:0003073
- Bilateral retinoblastoma with pineal tumor (intracranial); variant of hereditary retinoblastoma
- Inheritance: Autosomal dominant
- Evidence: Strong
Secondary Malignancies in RB1 Mutation Carriers:
- Osteosarcoma | MONDO:0002629 | Orphanet 668 | Evidence: Strong
- Small cell lung carcinoma | MONDO:0008433 | Orphanet 70573 | Evidence: Strong
- Medulloblastoma | MONDO:0007959 | Orphanet 616 | Evidence: Strong
- Melanoma | MONDO:0005105 | Evidence: Moderate
- Urinary bladder cancer | MONDO:0001187 | Evidence: Strong
- Ovarian cancer | MONDO:0008170 | Evidence: Strong
- Lung adenocarcinoma | MONDO:0005061 | Evidence: Strong
- Squamous cell carcinoma | MONDO:0005096 | Evidence: Strong
- Lip and oral cavity carcinoma | MONDO:0023644 | Evidence: Strong
- Lynch syndrome 4 | MONDO:0013699 | Orphanet 144 | Evidence: Moderate
Phenotype Associations (HPO Terms) — Top 30
| HPO ID | Phenotype |
|---|---|
| HP:0009919 | Retinoblastoma |
| HP:0000006 | Autosomal dominant inheritance |
| HP:0002669 | Osteosarcoma |
| HP:0000555 | Leukocoria (white pupil reflex) |
| HP:0002756 | Pathologic fracture |
| HP:0001909 | Leukemia |
| HP:0002665 | Lymphoma |
| HP:0009725 | Bladder neoplasm |
| HP:0006740 | Transitional cell carcinoma of bladder |
| HP:0007902 | Vitreous hemorrhage |
| HP:0010799 | Pinealoma |
| HP:0012254 | Ewing sarcoma |
| HP:0000518 | Cataract |
| HP:0000568 | Microphthalmia |
| HP:0000612 | Iris coloboma |
| HP:0100526 | Neoplasm of the lung |
| HP:0001442 | Somatic mosaicism |
| HP:0007862 | Retinal calcification |
| HP:0011531 | Vitritis |
| HP:0001249 | Intellectual disability |
| HP:0004322 | Short stature |
| HP:0001511 | Intrauterine growth retardation |
| HP:0001360 | Holoprosencephaly |
| HP:0002079 | Hypoplasia of corpus callosum |
| HP:0000243 | Trigonocephaly |
| HP:0000252 | Microcephaly |
| HP:0000175 | Cleft palate |
| HP:0001824 | Weight loss |
| HP:0003745 | Sporadic |
| HP:0025435 | Increased circulating lactate dehydrogenase |
Complex Disease/GWAS Associations — Top 8
| Trait | Gene | P-value | Study ID |
|---|---|---|---|
| Lymphocyte count | RB1 | 4.0 × 10⁻¹¹ | GCST90002388_164 |
| Birth weight (fetal locus) | ITM2B - RB1-DT | 7.0 × 10⁻¹¹ | GCST008362_41 |
| Birth weight | RB1 | 2.0 × 10⁻⁸ | GCST005146_24 |
| Post bronchodilator FEV1/FVC ratio | RB1 | 2.0 × 10⁻⁶ | GCST003264_7 |
| Chronic kidney disease | RB1 | 4.0 × 10⁻⁶ | GCST003140_5 |
| Diastolic blood pressure | RB1 | 2.0 × 10⁻⁷ | GCST012050_1 |
| Offspring birth weight | ITM2B - RB1-DT | 2.0 × 10⁻⁷ | GCST008363_106 |