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 | 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:RARA-BRD4 (FusionGDB2 ID:HG5914TG23476) |
Fusion Gene Summary for RARA-BRD4 |
 Fusion gene summary |
| Fusion gene information | Fusion gene name: RARA-BRD4 | Fusion gene ID: hg5914tg23476 | Hgene | Tgene | Gene symbol | RARA | BRD4 | Gene ID | 5914 | 23476 |
| Gene name | retinoic acid receptor alpha | bromodomain containing 4 | |
| Synonyms | NR1B1|RAR | CAP|HUNK1|HUNKI|MCAP | |
| Cytomap | ('RARA')('BRD4') 17q21.2 | 19p13.12 | |
| Type of gene | protein-coding | protein-coding | |
| Description | retinoic acid receptor alphaRAR-alphanuclear receptor subfamily 1 group B member 1nucleophosmin-retinoic acid receptor alpha fusion protein NPM-RAR long formretinoic acid nuclear receptor alpha variant 1retinoic acid nuclear receptor alpha variant 2 | bromodomain-containing protein 4chromosome-associated proteinmitotic chromosome-associated protein | |
| Modification date | 20200327 | 20200329 | |
| UniProtAcc | P10276 | O60885 | |
| Ensembl transtripts involved in fusion gene | ENST00000254066, ENST00000394089, ENST00000425707, ENST00000394081, ENST00000394086, ENST00000420042, | ||
| Fusion gene scores | * DoF score | 47 X 22 X 8=8272 | 15 X 19 X 13=3705 |
| # samples | 74 | 28 | |
| ** MAII score | log2(74/8272*10)=-3.48263900979862 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: RARA [Title/Abstract] AND BRD4 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint | RARA(38487646)-BRD4(15367035), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | RARA-BRD4 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. RARA-BRD4 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. RARA-BRD4 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. RARA-BRD4 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF. RARA-BRD4 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. RARA-BRD4 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF. RARA-BRD4 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. RARA-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 |
| Hgene | RARA | GO:0007165 | signal transduction | 2825025 |
| Hgene | RARA | GO:0030853 | negative regulation of granulocyte differentiation | 19917671 |
| Hgene | RARA | GO:0032689 | negative regulation of interferon-gamma production | 18416830 |
| Hgene | RARA | GO:0032720 | negative regulation of tumor necrosis factor production | 18416830 |
| Hgene | RARA | GO:0032736 | positive regulation of interleukin-13 production | 18416830 |
| Hgene | RARA | GO:0032753 | positive regulation of interleukin-4 production | 18416830 |
| Hgene | RARA | GO:0032754 | positive regulation of interleukin-5 production | 18416830 |
| Hgene | RARA | GO:0045630 | positive regulation of T-helper 2 cell differentiation | 18416830 |
| Hgene | RARA | GO:0045892 | negative regulation of transcription, DNA-templated | 20080953 |
| Hgene | RARA | GO:0045893 | positive regulation of transcription, DNA-templated | 18845237|19850744|20080953 |
| Hgene | RARA | GO:0045944 | positive regulation of transcription by RNA polymerase II | 19850744|21131358 |
| Hgene | RARA | GO:0071300 | cellular response to retinoic acid | 19917671 |
| Hgene | RARA | GO:0071391 | cellular response to estrogen stimulus | 20080953 |
| 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 |
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Fusion Gene ORF analysis for RARA-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 |
| 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 |
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Fusion Genomic Features for RARA-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) |
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Fusion Protein Features for RARA-BRD4 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:38487646/:15367035) - 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. |
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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| RARA | BRD4 |
| FUNCTION: Receptor for retinoic acid (PubMed:19850744, PubMed:16417524, PubMed:20215566). Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:28167758). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:28167758, PubMed:19398580). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:16417524). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:9267036, PubMed:19850744, PubMed:20215566). Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (PubMed:28167758). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (PubMed:28167758). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (By similarity). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (By similarity). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (PubMed:28167758). {ECO:0000250|UniProtKB:P11416, ECO:0000269|PubMed:16417524, ECO:0000269|PubMed:19398580, ECO:0000269|PubMed:19850744, ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:9267036}. | 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 |
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Fusion Gene Sequence for RARA-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. |
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Fusion Gene PPI Analysis for RARA-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 |
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Related Drugs for RARA-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 |
| Hgene | RARA | P10276 | DB00210 | Adapalene | Small molecule | Approved | |
| Hgene | RARA | P10276 | DB00210 | Adapalene | Small molecule | Approved | |
| Hgene | RARA | P10276 | DB00459 | Acitretin | Agonist | Small molecule | Approved |
| Hgene | RARA | P10276 | DB00459 | Acitretin | Agonist | Small molecule | Approved |
| Hgene | RARA | P10276 | DB00982 | Isotretinoin | Other/unknown | Small molecule | Approved |
| Hgene | RARA | P10276 | DB00982 | Isotretinoin | Other/unknown | Small molecule | Approved |
| Hgene | RARA | P10276 | DB00523 | Alitretinoin | Agonist | Small molecule | Approved|Investigational |
| Hgene | RARA | P10276 | DB00523 | Alitretinoin | Agonist | Small molecule | Approved|Investigational |
| Hgene | RARA | P10276 | DB00799 | Tazarotene | Agonist | Small molecule | Approved|Investigational |
| Hgene | RARA | P10276 | DB00799 | Tazarotene | Agonist | Small molecule | Approved|Investigational |
| Hgene | RARA | P10276 | DB12808 | Trifarotene | Agonist | Small molecule | Approved|Investigational |
| Hgene | RARA | P10276 | DB12808 | Trifarotene | Agonist | Small molecule | Approved|Investigational |
| Hgene | RARA | P10276 | DB00755 | Tretinoin | Small molecule | Approved|Investigational|Nutraceutical | |
| Hgene | RARA | P10276 | DB00755 | Tretinoin | Small molecule | Approved|Investigational|Nutraceutical |
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Related Diseases for RARA-BRD4 |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
| Hgene | RARA | C0023487 | Acute Promyelocytic Leukemia | 24 | CTD_human;ORPHANET |
| Hgene | RARA | C0036341 | Schizophrenia | 3 | PSYGENET |
| Hgene | RARA | C0006142 | Malignant neoplasm of breast | 1 | CTD_human |
| Hgene | RARA | C0009363 | Congenital ocular coloboma (disorder) | 1 | GENOMICS_ENGLAND |
| Hgene | RARA | C0010701 | Phyllodes Tumor | 1 | CTD_human |
| Hgene | RARA | C0085183 | Neoplasms, Second Primary | 1 | CTD_human |
| Hgene | RARA | C0086696 | Neoplasms, Therapy-Associated | 1 | CTD_human |
| Hgene | RARA | C0149940 | Sciatic Neuropathy | 1 | CTD_human |
| Hgene | RARA | C0154748 | Lesion of Sciatic Nerve | 1 | CTD_human |
| Hgene | RARA | C0206650 | Fibroadenoma | 1 | CTD_human |
| Hgene | RARA | C0242013 | Sciatic Neuritis | 1 | CTD_human |
| Hgene | RARA | C0525045 | Mood Disorders | 1 | PSYGENET |
| Hgene | RARA | C0600066 | Malignant Cystosarcoma Phyllodes | 1 | CTD_human |
| Hgene | RARA | C0678222 | Breast Carcinoma | 1 | CTD_human |
| Hgene | RARA | C0751924 | Neuralgia-Neuritis, Sciatic Nerve | 1 | CTD_human |
| Hgene | RARA | C0751925 | Sciatic Nerve Palsy | 1 | CTD_human |
| Hgene | RARA | C0877578 | Treatment related secondary malignancy | 1 | CTD_human |
| Hgene | RARA | C1257931 | Mammary Neoplasms, Human | 1 | CTD_human |
| Hgene | RARA | C1458155 | Mammary Neoplasms | 1 | CTD_human |
| Hgene | RARA | C2239176 | Liver carcinoma | 1 | CTD_human |
| Hgene | RARA | 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 |
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