|
||||||
|
 | Fusion Gene Summary |
| Fusion Gene ORF analysis |
| Fusion Genomic Features |
| Fusion Protein Features |
| Fusion Gene Sequence |
| Fusion Gene PPI analysis |
| Related Drugs |
| Related Diseases |
Fusion gene:NOTCH3-BRD4 (FusionGDB2 ID:HG4854TG23476) |
Fusion Gene Summary for NOTCH3-BRD4 |
 Fusion gene summary |
| Fusion gene information | Fusion gene name: NOTCH3-BRD4 | Fusion gene ID: hg4854tg23476 | Hgene | Tgene | Gene symbol | NOTCH3 | BRD4 | Gene ID | 4854 | 23476 |
| Gene name | notch receptor 3 | bromodomain containing 4 | |
| Synonyms | CADASIL|CADASIL1|CASIL|IMF2|LMNS | CAP|HUNK1|HUNKI|MCAP | |
| Cytomap | ('NOTCH3')('BRD4') 19p13.12 | 19p13.12 | |
| Type of gene | protein-coding | protein-coding | |
| Description | neurogenic locus notch homolog protein 3Notch homolog 3notch 3 | bromodomain-containing protein 4chromosome-associated proteinmitotic chromosome-associated protein | |
| Modification date | 20200329 | 20200329 | |
| UniProtAcc | Q9UM47 | O60885 | |
| Ensembl transtripts involved in fusion gene | ENST00000263388, | ENST00000263388, | |
| Fusion gene scores | * DoF score | 15 X 17 X 11=2805 | 15 X 19 X 13=3705 |
| # samples | 18 | 28 | |
| ** MAII score | log2(18/2805*10)=-3.96193195916648 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(28/3705*10)=-3.72597481024823 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context | PubMed: NOTCH3 [Title/Abstract] AND BRD4 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint | NOTCH3(15308311)-BRD4(15360101), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | NOTCH3-BRD4 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. NOTCH3-BRD4 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF. NOTCH3-BRD4 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. NOTCH3-BRD4 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF. NOTCH3-BRD4 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. NOTCH3-BRD4 seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF. | ||
| * DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
| Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Tgene | BRD4 | GO:0032968 | positive regulation of transcription elongation from RNA polymerase II promoter | 19103749|23086925 |
| Tgene | BRD4 | GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB signaling | 19103749 |
| Tgene | BRD4 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 23086925|23317504|24360279 |
| Tgene | BRD4 | GO:0050727 | regulation of inflammatory response | 19103749 |
| Tgene | BRD4 | GO:1901407 | regulation of phosphorylation of RNA polymerase II C-terminal domain | 23086925 |
| Fusion gene information * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| Source | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | CESC | TCGA-HM-A6W2-01A | NOTCH3 | chr19 | 15308311 | - | BRD4 | chr19 | 15355573 | - |
| ChimerDB4 | CESC | TCGA-HM-A6W2-01A | NOTCH3 | chr19 | 15308311 | - | BRD4 | chr19 | 15360101 | - |
| ChimerDB4 | UCEC | TCGA-B5-A0JN-01A | NOTCH3 | chr19 | 15299800 | - | BRD4 | chr19 | 15360101 | - |
Top |
Fusion Gene ORF analysis for NOTCH3-BRD4 |
| Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| ORF | Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| 5CDS-intron | ENST00000263388 | ENST00000263377 | NOTCH3 | chr19 | 15308311 | - | BRD4 | chr19 | 15360101 | - |
| 5CDS-intron | ENST00000263388 | ENST00000263377 | NOTCH3 | chr19 | 15299800 | - | BRD4 | chr19 | 15360101 | - |
| 5CDS-intron | ENST00000263388 | ENST00000360016 | NOTCH3 | chr19 | 15308311 | - | BRD4 | chr19 | 15355573 | - |
| 5CDS-intron | ENST00000263388 | ENST00000360016 | NOTCH3 | chr19 | 15308311 | - | BRD4 | chr19 | 15360101 | - |
| 5CDS-intron | ENST00000263388 | ENST00000360016 | NOTCH3 | chr19 | 15299800 | - | BRD4 | chr19 | 15360101 | - |
| 5CDS-intron | ENST00000263388 | ENST00000371835 | NOTCH3 | chr19 | 15308311 | - | BRD4 | chr19 | 15355573 | - |
| 5CDS-intron | ENST00000263388 | ENST00000371835 | NOTCH3 | chr19 | 15308311 | - | BRD4 | chr19 | 15360101 | - |
| 5CDS-intron | ENST00000263388 | ENST00000371835 | NOTCH3 | chr19 | 15299800 | - | BRD4 | chr19 | 15360101 | - |
| 5CDS-intron | ENST00000263388 | ENST00000602230 | NOTCH3 | chr19 | 15308311 | - | BRD4 | chr19 | 15355573 | - |
| 5CDS-intron | ENST00000263388 | ENST00000602230 | NOTCH3 | chr19 | 15308311 | - | BRD4 | chr19 | 15360101 | - |
| 5CDS-intron | ENST00000263388 | ENST00000602230 | NOTCH3 | chr19 | 15299800 | - | BRD4 | chr19 | 15360101 | - |
| Frame-shift | ENST00000263388 | ENST00000263377 | NOTCH3 | chr19 | 15308311 | - | BRD4 | chr19 | 15355573 | - |
| ORFfinder result based on the fusion transcript sequence of in-frame fusion genes. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
| DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
Top |
Fusion Genomic Features for NOTCH3-BRD4 |
| FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints. |
| Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | 1-p | p (fusion gene breakpoint) |
Top |
Fusion Protein Features for NOTCH3-BRD4 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:15308311/:15360101) - FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels. - How to search 1. Put your fusion gene symbol. 2. Press the tab key until there will be shown the breakpoint information filled. 4. Go down and press 'Search' tab twice. 4. Go down to have the hyperlink of the search result. 5. Click the hyperlink. 6. See the FGviewer result for your fusion gene. |
 |
| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| NOTCH3 | BRD4 |
| FUNCTION: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). {ECO:0000250|UniProtKB:Q9R172, ECO:0000269|PubMed:15350543}. | FUNCTION: Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure (PubMed:23589332, PubMed:23317504, PubMed:22334664). During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters. Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6. BRD4 and JMJD6 are required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II (PubMed:23589332, PubMed:19596240, PubMed:16109377, PubMed:16109376, PubMed:24360279). Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II (PubMed:23086925). According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo (PubMed:22509028). In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B (PubMed:19103749). Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters (PubMed:23317504). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:19596240, ECO:0000269|PubMed:22334664, ECO:0000269|PubMed:22509028, ECO:0000269|PubMed:23086925, ECO:0000269|PubMed:23317504, ECO:0000269|PubMed:23589332, ECO:0000269|PubMed:24360279}.; FUNCTION: [Isoform B]: Acts as a chromatin insulator in the DNA damage response pathway. Inhibits DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones, leading to chromatin structure remodeling, insulating the region from DNA damage response by limiting spreading of histone H2AX/H2A.x phosphorylation. {ECO:0000269|PubMed:23728299}. |
| Retention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - In-frame and retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| - In-frame and not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
Top |
Fusion Gene Sequence for NOTCH3-BRD4 |
| For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
Top |
Fusion Gene PPI Analysis for NOTCH3-BRD4 |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160) |
| Hgene | Hgene's interactors | Tgene | Tgene's interactors |
| - Retained PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
| - Retained PPIs, but lost function due to frame-shift fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
Top |
Related Drugs for NOTCH3-BRD4 |
| Drugs targeting genes involved in this fusion gene. (DrugBank Version 5.1.8 2021-05-08) |
| Partner | Gene | UniProtAcc | DrugBank ID | Drug name | Drug activity | Drug type | Drug status |
Top |
Related Diseases for NOTCH3-BRD4 |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
| Hgene | NOTCH3 | C4551768 | CEREBRAL ARTERIOPATHY, AUTOSOMAL DOMINANT, WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY, TYPE 1 | 24 | GENOMICS_ENGLAND;UNIPROT |
| Hgene | NOTCH3 | C0006142 | Malignant neoplasm of breast | 1 | CTD_human |
| Hgene | NOTCH3 | C0007114 | Malignant neoplasm of skin | 1 | CTD_human |
| Hgene | NOTCH3 | C0007131 | Non-Small Cell Lung Carcinoma | 1 | CTD_human |
| Hgene | NOTCH3 | C0007137 | Squamous cell carcinoma | 1 | CTD_human |
| Hgene | NOTCH3 | C0017636 | Glioblastoma | 1 | CTD_human |
| Hgene | NOTCH3 | C0024121 | Lung Neoplasms | 1 | CTD_human |
| Hgene | NOTCH3 | C0036572 | Seizures | 1 | GENOMICS_ENGLAND |
| Hgene | NOTCH3 | C0037286 | Skin Neoplasms | 1 | CTD_human |
| Hgene | NOTCH3 | C0038454 | Cerebrovascular accident | 1 | GENOMICS_ENGLAND |
| Hgene | NOTCH3 | C0085584 | Encephalopathies | 1 | GENOMICS_ENGLAND |
| Hgene | NOTCH3 | C0149931 | Migraine Disorders | 1 | GENOMICS_ENGLAND |
| Hgene | NOTCH3 | C0206648 | Myofibromatosis | 1 | GENOMICS_ENGLAND |
| Hgene | NOTCH3 | C0242379 | Malignant neoplasm of lung | 1 | CTD_human |
| Hgene | NOTCH3 | C0279626 | Squamous cell carcinoma of esophagus | 1 | CTD_human |
| Hgene | NOTCH3 | C0334588 | Giant Cell Glioblastoma | 1 | CTD_human |
| Hgene | NOTCH3 | C0338656 | Impaired cognition | 1 | GENOMICS_ENGLAND |
| Hgene | NOTCH3 | C0344487 | Lateral meningocele | 1 | ORPHANET |
| Hgene | NOTCH3 | C0432284 | Infantile myofibromatosis | 1 | CTD_human;GENOMICS_ENGLAND;ORPHANET |
| Hgene | NOTCH3 | C0497327 | Dementia | 1 | GENOMICS_ENGLAND |
| Hgene | NOTCH3 | C0678222 | Breast Carcinoma | 1 | CTD_human |
| Hgene | NOTCH3 | C0887833 | Carcinoma, Pancreatic Ductal | 1 | CTD_human |
| Hgene | NOTCH3 | C1257931 | Mammary Neoplasms, Human | 1 | CTD_human |
| Hgene | NOTCH3 | C1458155 | Mammary Neoplasms | 1 | CTD_human |
| Hgene | NOTCH3 | C1621958 | Glioblastoma Multiforme | 1 | CTD_human |
| Hgene | NOTCH3 | C1851710 | LATERAL MENINGOCELE SYNDROME | 1 | CTD_human;ORPHANET |
| Hgene | NOTCH3 | C2239176 | Liver carcinoma | 1 | CTD_human |
| Hgene | NOTCH3 | C3809084 | MYOFIBROMATOSIS, INFANTILE, 2 | 1 | GENOMICS_ENGLAND;UNIPROT |
| Hgene | NOTCH3 | C4704874 | Mammary Carcinoma, Human | 1 | CTD_human |
| Tgene | C0017636 | Glioblastoma | 2 | CTD_human | |
| Tgene | C0334588 | Giant Cell Glioblastoma | 2 | CTD_human | |
| Tgene | C1621958 | Glioblastoma Multiforme | 2 | CTD_human | |
| Tgene | C0002170 | Alopecia | 1 | CTD_human | |
| Tgene | C0007102 | Malignant tumor of colon | 1 | CTD_human | |
| Tgene | C0009375 | Colonic Neoplasms | 1 | CTD_human | |
| Tgene | C0018798 | Congenital Heart Defects | 1 | GENOMICS_ENGLAND | |
| Tgene | C0019193 | Hepatitis, Toxic | 1 | CTD_human | |
| Tgene | C0020507 | Hyperplasia | 1 | CTD_human | |
| Tgene | C0020542 | Pulmonary Hypertension | 1 | CTD_human | |
| Tgene | C0025149 | Medulloblastoma | 1 | CTD_human | |
| Tgene | C0025958 | Microcephaly | 1 | GENOMICS_ENGLAND | |
| Tgene | C0029463 | Osteosarcoma | 1 | CTD_human | |
| Tgene | C0033578 | Prostatic Neoplasms | 1 | CTD_human | |
| Tgene | C0040136 | Thyroid Neoplasm | 1 | CTD_human | |
| Tgene | C0085413 | Polycystic Kidney, Autosomal Dominant | 1 | CTD_human | |
| Tgene | C0086873 | Pseudopelade | 1 | CTD_human | |
| Tgene | C0151468 | Thyroid Gland Follicular Adenoma | 1 | CTD_human | |
| Tgene | C0162311 | Androgenetic Alopecia | 1 | CTD_human | |
| Tgene | C0205833 | Medullomyoblastoma | 1 | CTD_human | |
| Tgene | C0263477 | Female pattern alopecia (disorder) | 1 | CTD_human | |
| Tgene | C0270972 | Cornelia De Lange Syndrome | 1 | CTD_human | |
| Tgene | C0278510 | Childhood Medulloblastoma | 1 | CTD_human | |
| Tgene | C0278876 | Adult Medulloblastoma | 1 | CTD_human | |
| Tgene | C0376358 | Malignant neoplasm of prostate | 1 | CTD_human | |
| Tgene | C0549473 | Thyroid carcinoma | 1 | CTD_human | |
| Tgene | C0751291 | Desmoplastic Medulloblastoma | 1 | CTD_human | |
| Tgene | C0860207 | Drug-Induced Liver Disease | 1 | CTD_human | |
| Tgene | C0887850 | Polycystic Kidney, Type 1 Autosomal Dominant Disease | 1 | CTD_human | |
| Tgene | C1262760 | Hepatitis, Drug-Induced | 1 | CTD_human | |
| Tgene | C1275668 | Melanotic medulloblastoma | 1 | CTD_human | |
| Tgene | C1707291 | NUT midline carcinoma | 1 | ORPHANET | |
| Tgene | C1802395 | Congenital muscular hypertrophy-cerebral syndrome | 1 | CTD_human | |
| Tgene | C1853099 | Cornelia de Lange Syndrome 3 | 1 | CTD_human | |
| Tgene | C2751306 | Polycystic kidney disease, type 2 | 1 | CTD_human | |
| Tgene | C3658290 | Drug-Induced Acute Liver Injury | 1 | CTD_human | |
| Tgene | C3714756 | Intellectual Disability | 1 | GENOMICS_ENGLAND | |
| Tgene | C4025871 | Abnormality of the face | 1 | GENOMICS_ENGLAND | |
| Tgene | C4083212 | Alopecia, Male Pattern | 1 | CTD_human | |
| Tgene | C4277682 | Chemical and Drug Induced Liver Injury | 1 | CTD_human | |
| Tgene | C4279912 | Chemically-Induced Liver Toxicity | 1 | CTD_human | |
| Tgene | C4551851 | Cornelia de Lange Syndrome 1 | 1 | CTD_human |
Copyright 2021-Present -The University of Texas Health Science Center at Houston (UTHealth)
Web File Viewing | Emergency Information |Campus Carry|Site Policies