RBL1
protein-codingRB transcriptional corepressor like 1
Gene summary
The protein encoded by this gene is similar in sequence and possibly function to the product of the retinoblastoma 1 (RB1) gene. The RB1 gene product is a tumor suppressor protein that appears to be involved in cell cycle regulation, as it is phosphorylated in the S to M phase transition and is dephosphorylated in the G1 phase of the cell cycle. Both the RB1 protein and the product of this gene can form a complex with adenovirus E1A protein and SV40 large T-antigen, with the SV40 large T-antigen binding only to the unphosphorylated form of each protein. In addition, both proteins can inhibit the transcription of cell cycle genes containing E2F binding sites in their promoters. Due to the sequence and biochemical similarities with the RB1 protein, it is thought that the protein encoded by this gene may also be a tumor suppressor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~99.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RBL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002895.5. 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 | 1 | 1 | 2 | |||
| missense | 148 | 2 | 1 | 151 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 152 | 2 | 2 | 156 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002886.2 | 22 | MANE Select | |
| Ensembl | ENSP00000362768.3 | 22 | MANE Select | |
| RefSeq | NP_001310210.1 | 13 | Standard | |
| RefSeq | NP_001310211.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TGF-beta signaling pathway - Homo sapiens (human)
- Cell cycle - Homo sapiens (human)
- Viral carcinogenesis - Homo sapiens (human)
- Cellular senescence - Homo sapiens (human)
- Human papillomavirus infection - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- chromatin organization
- cell cycle
- regulation of mitotic cell cycle
- negative regulation of gene expression
Molecular Function
- RNA polymerase II regulatory region DNA binding
- RNA polymerase II activating transcription factor binding
- protein binding
- transcription factor binding
- promoter-specific chromatin binding
Cellular Component
- chromatin
- nucleus
- nucleoplasm
- transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373664
- Coding exons
- 22
- Length
- 99647
- Individuals with no LoFs
- 125626
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 122
- Defined
- 125748
- p
- 0.000485
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.22 | 492 | 574 | 0.857 | 0.0000301 | 7006 |
| Missense (PolyPhen) | 167 | 218.87 | 0.76301 | 2679 | ||
| Synonymous | 1.05 | 178 | 197 | 0.905 | 0.0000100 | 2027 |
| Loss of Function | 3.28 | 28 | 54.0 | 0.518 | 0.00000297 | 687 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00031 | rare |
| Latino/Admixed American | 0.00041 | 0.00040 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.000096 | 0.000092 | rare |
| European (Non-Finnish) | 0.00073 | 0.00072 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys- 20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation. Forms a complex with adenovirus E1A and with SV40 large T antigen. May bind and modulate functionally certain cellular proteins with which T and E1A compete for pocket binding. May act as a tumor suppressor.;
Recessive Scores
- pRec
- 0.208
Intolerance Scores
- LoFtool
- 0.116
- RVIS EVS
- -0.82
- RVIS percentile EVS
- 11.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.774
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |