RBPJ
protein-codingrecombination signal binding protein for immunoglobulin kappa J region, the group of IPT domain containing|PTF1 complex
Gene summary
The protein encoded by this gene is a transcriptional regulator important in the Notch signaling pathway. The encoded protein acts as a repressor when not bound to Notch proteins and an activator when bound to Notch proteins. It is thought to function by recruiting chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins to Notch signaling pathway genes. Several transcript variants encoding different isoforms have been found for this gene, and several pseudogenes of this gene exist on chromosome 9. [provided by RefSeq, Oct 2013]
- IGKJRB1
- RBPSUH
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~271.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0013895
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0013895
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0013895
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0013895
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007034
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Dermatologic; Musculoskeletal; Neurologic
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 RBPJ variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015874.6. 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 | 3 | 39 | 4 | 46 | ||
| missense | 2 | 5 | 65 | 8 | 80 | |
| nonsense | 5 | 5 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 2 | 5 | 79 | 47 | 4 | 137 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056958.3 | 11 | MANE Select | |
| Ensembl | ENSP00000347659.4 | 11 | MANE Select | |
| RefSeq | NP_001350506.1 | 9 | Standard | |
| RefSeq | NP_001361329.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rbpjb | Danio rerio | Structure: Rohon-Beard neuron Quality: increased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Th1 and Th2 cell differentiation - Homo sapiens (human)
- Viral carcinogenesis - Homo sapiens (human)
- Notch signaling pathway - Homo sapiens (human)
- Epstein-Barr virus infection - Homo sapiens (human)
- Human papillomavirus infection - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- angiogenesis
- somitogenesis
- epithelial to mesenchymal transition
- blood vessel remodeling
Molecular Function
- recombinase activity
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA polymerase II repressing transcription factor binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
Cellular Component
- MAML1-RBP-Jkappa- ICN1 complex
- nucleus
- nucleoplasm
- transcription factor complex
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000342295
- Coding exons
- 11
- Length
- 271465
- Individuals with no LoFs
- 125570
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125572
- p
- 0.00000796
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.57 | 109 | 276 | 0.395 | 0.0000142 | 3244 |
| Missense (PolyPhen) | 6 | 99.012 | 0.060599 | 1328 | ||
| Synonymous | -0.694 | 106 | 97.3 | 1.09 | 0.00000517 | 946 |
| Loss of Function | 4.77 | 3 | 32.2 | 0.0931 | 0.00000212 | 332 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional regulator that plays a central role in Notch signaling, a signaling pathway involved in cell-cell communication that regulates a broad spectrum of cell-fate determinations. Acts as a transcriptional repressor when it is not associated with Notch proteins. When associated with some NICD product of Notch proteins (Notch intracellular domain), it acts as a transcriptional activator that activates transcription of Notch target genes. Probably represses or activates transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively. Specifically binds to the immunoglobulin kappa-type J segment recombination signal sequence. Binds specifically to methylated DNA (PubMed:21991380). Binds to the oxygen responsive element of COX4I2 and activates its transcription under hypoxia conditions (4% oxygen) (PubMed:23303788). Negatively regulates the phagocyte oxidative burst in response to bacterial infection by repressing transcription of NADPH oxidase subunits (By similarity). {ECO:0000250|UniProtKB:P31266, ECO:0000269|PubMed:21991380, ECO:0000269|PubMed:23303788}.;
- Disease
- DISEASE: Adams-Oliver syndrome 3 (AOS3) [MIM:614814]: An autosomal dominant form of Adams-Oliver syndrome, a disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins. AOS3 patients manifest characteristic vertex scalp defects and terminal limb defects, but without congenital heart defects, other associated defects, or immune defects. {ECO:0000269|PubMed:22883147}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.364
Intolerance Scores
- LoFtool
- 0.0815
- RVIS EVS
- -0.52
- RVIS percentile EVS
- 21.2
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |