RBPJ
recombination signal binding protein for immunoglobulin kappa J region, the group of IPT domain containing|PTF1 complex
Basic information
Region (hg38): 4:26163454-26435131
Previous symbols: [ "IGKJRB1", "RBPSUH" ]
Links
Phenotypes
GenCC
Source:
- Adams-Oliver syndrome 3 (Moderate), mode of inheritance: AD
- Adams-Oliver syndrome (Supportive), mode of inheritance: AD
- Adams-Oliver syndrome 3 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Adams-Oliver syndrome 3 | AD | General | 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 | Dermatologic; Musculoskeletal; Neurologic | 22883147 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (112 variants)
- Adams-Oliver syndrome 3 (8 variants)
- Type 2 diabetes mellitus (7 variants)
- Inborn genetic diseases (7 variants)
- RBPJ-related condition (2 variants)
- not specified (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RBPJ gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 23 | 29 | ||||
| missense | 35 | 41 | ||||
| nonsense | 3 | |||||
| start loss | 1 | |||||
| frameshift | 2 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region ? | 3 | 3 | 4 | 10 | ||
| non coding ? | 21 | 23 | 45 | |||
| Total | 0 | 5 | 46 | 45 | 27 |
Variants in RBPJ
This is a list of pathogenic ClinVar variants found in the RBPJ region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RBPJ | protein_coding | protein_coding | ENST00000342295 | 11 | 271465 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.00147 | 125570 | 0 | 2 | 125572 | 0.00000796 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.57 | 109 | 276 | 0.395 | 0.0000142 | 3244 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
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.;
- Pathway
- 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);NOTCH-Core;Neural Crest Differentiation;Notch Signaling Pathway;Canonical and Non-canonical Notch signaling;PTF1A related regulatory pathway;EMT transition in Colorectal Cancer;Notch Signaling Pathway;Notch Signaling Pathway;Notch;Disease;RUNX3 regulates NOTCH signaling;Signal Transduction;Gene expression (Transcription);Transcriptional regulation by RUNX3;proteolysis and signaling pathway of notch;segmentation clock;Generic Transcription Pathway;RNA Polymerase II Transcription;Notch-HLH transcription pathway;Notch;NICD traffics to nucleus;Pre-NOTCH Transcription and Translation;Pre-NOTCH Expression and Processing;Signaling by NOTCH1;NOTCH2 intracellular domain regulates transcription;Signaling by NOTCH2;NOTCH3 Intracellular Domain Regulates Transcription;Signaling by NOTCH3;Signaling by NOTCH;Notch signaling pathway;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Notch-mediated HES/HEY network;Diseases of signal transduction;NOTCH1 Intracellular Domain Regulates Transcription;Presenilin action in Notch and Wnt signaling
(Consensus)
Recessive Scores
- pRec
- 0.364
Intolerance Scores
- loftool
- 0.0815
- rvis_EVS
- -0.52
- rvis_percentile_EVS
- 21.2
Haploinsufficiency Scores
- pHI
- 0.928
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.611
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rbpj
- Phenotype
- integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; digestive/alimentary phenotype; muscle phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; pigmentation phenotype; embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- rbpjb
- Affected structure
- Rohon-Beard neuron
- Phenotype tag
- abnormal
- Phenotype quality
- increased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;angiogenesis;somitogenesis;epithelial to mesenchymal transition;blood vessel remodeling;inflammatory response to antigenic stimulus;secondary heart field specification;outflow tract morphogenesis;endocardium morphogenesis;aortic valve development;pulmonary valve development;epithelial to mesenchymal transition involved in endocardial cushion formation;cardiac left ventricle morphogenesis;ventricular trabecula myocardium morphogenesis;regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation;DNA recombination;transcription initiation from RNA polymerase II promoter;humoral immune response;Notch signaling pathway;positive regulation of transcription of Notch receptor target;negative regulation of cell population proliferation;auditory receptor cell fate commitment;epidermal cell fate specification;positive regulation of gene expression;pituitary gland development;B cell differentiation;keratinocyte differentiation;negative regulation of ossification;positive regulation of BMP signaling pathway;somatic stem cell population maintenance;dorsal aorta morphogenesis;atrioventricular canal development;defense response to bacterium;myeloid dendritic cell differentiation;negative regulation of cell differentiation;positive regulation of Notch signaling pathway;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of timing of cell differentiation;sebaceous gland development;hair follicle maturation;positive regulation of cardiac muscle cell proliferation;ventricular septum morphogenesis;Clara cell differentiation;labyrinthine layer blood vessel development;arterial endothelial cell fate commitment;Notch signaling involved in heart development;positive regulation of transcription from RNA polymerase II promoter in response to hypoxia;blood vessel lumenization;interleukin-4 secretion;blood vessel endothelial cell fate specification;negative regulation of cold-induced thermogenesis;positive regulation of ERBB signaling pathway;positive regulation of ephrin receptor signaling pathway;positive regulation of canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment;positive regulation of cell proliferation involved in heart morphogenesis
- Cellular component
- MAML1-RBP-Jkappa- ICN1 complex;nucleus;nucleoplasm;transcription factor complex;nucleolus;cytoplasm;transcriptional repressor complex
- 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;DNA binding;chromatin binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;sequence-specific DNA binding;protein N-terminus binding;repressing transcription factor binding