RBBP7
protein-codingRB binding protein 7, chromatin remodeling factor, the group of EMSY complex|NuRD complex subunits|WD repeat domain containing|SIN3 histone deacetylase complex subunits|Polycomb repressive complex 2|NURF complex
Gene summary
This protein is a ubiquitously expressed nuclear protein and belongs to a highly conserved subfamily of WD-repeat proteins. It is found among several proteins that binds directly to retinoblastoma protein, which regulates cell proliferation. The encoded protein is found in many histone deacetylase complexes, including mSin3 co-repressor complex. It is also present in protein complexes involved in chromatin assembly. This protein can interact with BRCA1 tumor-suppressor gene and may have a role in the regulation of cell proliferation and differentiation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0976123
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Genitourinary
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RBBP7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002893.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 16 | 1 | 17 | |||
| missense | 73 | 73 | ||||
| nonsense | 6 | 6 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 26 | 26 | ||||
| Total | 1 | 0 | 121 | 0 | 1 | 123 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002884.1 | 12 | MANE Select | |
| Ensembl | ENSP00000369427.3 | 12 | MANE Select | |
| RefSeq | NP_001185648.1 | 12 | Standard | |
| Ensembl | ENSP00000369424.4 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Retinoblastoma (RB) in Cancer
- Interactome of polycomb repressive complex 2 (PRC2)
- ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
- Positive epigenetic regulation of rRNA expression
- Signal Transduction
Biological Process
- negative regulation of transcription by RNA polymerase II
- DNA replication
- multicellular organism development
- cell population proliferation
- histone deacetylation
Molecular Function
- RNA binding
- histone deacetylase activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- NuRD complex
- ESC/E(Z) complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380084
- Coding exons
- 12
- Length
- 31132
- Individuals with no LoFs
- 112025
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 112026
- p
- 0.00000446
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.79 | 72 | 176 | 0.409 | 0.0000132 | 3090 |
| Missense (PolyPhen) | 18 | 82.883 | 0.21717 | 1392 | ||
| Synonymous | -0.805 | 75 | 66.6 | 1.13 | 0.00000531 | 887 |
| Loss of Function | 3.59 | 1 | 17.0 | 0.0590 | 0.00000113 | 301 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000013 | 0.0000094 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; and the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex. {ECO:0000269|PubMed:10866654}.;
Recessive Scores
- pRec
- 0.314
Intolerance Scores
- LoFtool
- 0.112
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 42.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.437
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |