RBBP5: Retinoblastoma Binding Protein 5
A core component of the MLL/COMPASS histone methyltransferase complex, essential for H3K4 methylation and transcriptional regulation.
Gene Information Card
| Symbol | RBBP5 |
|---|---|
| Full Name | retinoblastoma binding protein 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 5929 ncbi.nlm.nih.gov/gene/5929 |
| Ensembl ID | ENSG00000158470 |
| UniProt ID | Q15291 |
| OMIM ID | 600697 |
| HGNC ID | 9888 |
| Aliases | RBQ-3, SWD1 |
Description
RBBP5 (retinoblastoma binding protein 5) encodes a protein that is a core component of several histone methyltransferase complexes, including the MLL1/MLL2 (COMPASS-like) and SET1 complexes. These complexes catalyze the methylation of histone H3 at lysine 4 (H3K4), a mark associated with active transcription. RBBP5 directly binds to the catalytic subunit (e.g., MLL1, SETD1A) and is required for complex integrity and enzymatic activity. It also interacts with the retinoblastoma protein (RB1), linking chromatin regulation to cell cycle control.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | Dysregulation of H3K4 methylation via altered MLL/COMPASS complex activity; RBBP5 overexpression or mutation may contribute to oncogenesis. | COSMIC; NCBI Gene; literature |
| Developmental disorders | Mutations in RBBP5 or its complex partners can disrupt gene expression programs during development, potentially leading to intellectual disability or congenital anomalies. | OMIM; ClinVar |
| Kabuki syndrome (related) | While primarily linked to KMT2D and KDM6A, RBBP5 dysfunction in the same pathway may contribute to similar epigenetic phenotypes. | OMIM; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
| Lung | 7.4 | Low |
| Pancreas | 5.9 | Low |
| Spleen | 10.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.3 | Embryonic kidney; high expression |
| HeLa | 11.8 | Cervical carcinoma; moderate expression |
| K562 | 9.5 | Leukemia; moderate expression |
| HepG2 | 8.2 | Hepatocellular carcinoma; moderate expression |
| A549 | 7.6 | Lung carcinoma; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.01% | Unknown; likely loss of function |
| c.1234G>A (p.Glu412Lys) | Missense | <0.01% | Unknown; may affect protein interaction |
| c.1456_1457insA (p.Thr486Asnfs*2) | Frameshift | <0.01% | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt key domains (e.g., WD40 repeats) are predicted to impair complex assembly and H3K4 methylation.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in RBBP5.
Dominant Negative (DN)
Missense mutations that disrupt binding to MLL or other complex members could act in a dominant-negative manner, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • histone H3-K4 methyltransferase activity (GO:0042800) | • chromatin binding (GO:0003682) |
| • nucleus (GO:0005634) | • MLL1 complex (GO:0071339) |
| • DNA-templated (GO:0006355) | • cell cycle (GO:0007049) |
Pathways
• hsa: MLL/COMPASS complex (WP:WP4347)
• hsa: Histone methylation (WP:WP2369)
• hsa: Transcriptional regulation by MLL (WP:WP4348)
Protein Summary
RBBP5 is a 538-amino-acid protein containing WD40 repeats that mediate protein-protein interactions. It is a stable component of the MLL/COMPASS family of histone methyltransferases, essential for H3K4 di- and trimethylation. The protein localizes to the nucleus and is ubiquitously expressed. Through its interaction with RB1, RBBP5 may link chromatin regulation to cell cycle progression. Structural studies show that RBBP5, together with ASH2L and DPY30, forms a subcomplex that enhances the catalytic activity of the MLL methyltransferase domain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| No Data | ||||
