RBL2
protein-codingRB transcriptional corepressor like 2
Gene summary
Enables promoter-specific chromatin binding activity. Involved in regulation of lipid kinase activity. Acts upstream of or within negative regulation of gene expression. Located in nucleolus and nucleoplasm. Implicated in Brunet-Wagner neurodevelopmental syndrome. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~57.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0859217
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0859217
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Neurologic; Ophthalmologic
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 RBL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005611.4. 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 | 1 | 7 | 2 | 10 | ||
| missense | 168 | 2 | 2 | 172 | ||
| nonsense | 1 | 2 | 1 | 4 | ||
| start loss | 0 | |||||
| frameshift | 2 | 4 | 6 | |||
| splice donor/acceptor (+/-2bp) | 3 | 7 | 10 | |||
| Total | 6 | 6 | 177 | 9 | 4 | 202 |
Highest pathogenic variant AF is 0.000027398522
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005602.3 | 22 | MANE Select | |
| Ensembl | ENSP00000262133.6 | 22 | MANE Select | |
| RefSeq | NP_001310537.1 | 22 | Standard | |
| RefSeq | NP_001310538.1 | 21 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Cell cycle - Homo sapiens (human)
- FoxO signaling pathway - Homo sapiens (human)
- Viral carcinogenesis - Homo sapiens (human)
- Cellular senescence - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- chromatin organization
- DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
- 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
- promoter-specific chromatin binding
Cellular Component
- chromatin
- nucleus
- nucleoplasm
- transcription factor complex
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262133
- Coding exons
- 22
- Length
- 57673
- Individuals with no LoFs
- 125712
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125747
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.23 | 519 | 604 | 0.860 | 0.0000307 | 7489 |
| Missense (PolyPhen) | 106 | 171.98 | 0.61635 | 2138 | ||
| Synonymous | 1.61 | 178 | 208 | 0.857 | 0.0000102 | 2152 |
| Loss of Function | 5.80 | 8 | 54.0 | 0.148 | 0.00000260 | 698 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00028 | 0.00026 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00012 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
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, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor.;
Intolerance Scores
- LoFtool
- 0.0964
- RVIS EVS
- -0.73
- RVIS percentile EVS
- 14.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.648
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |