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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene Breakpoints

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Tumorigenic MoA (Mechanism of Action) Scenarios of Fusion Geness

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Fusion Genomic Features

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Fusion Gene ORF Annotations

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Fusion Protein Retained/Non-Retained Functional Features

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Fusion Transcript Sequences

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Fusion Protein Sequences

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Personalized Fusion Protein Sequences

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Fusion Gene Expressed Samples

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Related Drugs

Fusion gene:BRD4_ZC3H15 (FusionGDB2 ID:HG23476TG55854)

Fusion Gene Summary for BRD4_ZC3H15

check button Fusion gene summary
Fusion gene informationFusion gene name: BRD4_ZC3H15
Fusion gene ID: hg23476tg55854
HgeneTgene
Gene symbol

BRD4

ZC3H15

Gene ID

23476

55854

Gene namebromodomain containing 4zinc finger CCCH-type containing 15
SynonymsCAP|CDLS6|FSHRG4|HUNK1|HUNKI|MCAPDFRP1|HT010|LEREPO4|MSTP012
Cytomap

19p13.12

2q32.1

Type of geneprotein-codingprotein-coding
Descriptionbromodomain-containing protein 4chromosome-associated proteinfemale sterile homeotic related gene 4mitotic chromosome-associated proteinzinc finger CCCH domain-containing protein 15DRG family-regulatory protein 1likely ortholog of mouse immediate early response erythropoietin 4
Modification date2024041620240305
UniProtAcc

O60885

.
Ensembl transtripts involved in fusion geneENST00000360016, ENST00000263377, 
ENST00000371835, ENST00000602230, 
Fusion gene scores* DoF score* DoF score (Degree of Frequency) = # partners X # break points X # disease types
45 X 81 X 27=98415
* DoF score (Degree of Frequency) = # partners X # break points X # disease types
3 X 10 X 6=180
# samples 1179
** MAII score** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)
log2(117/98415*10)=-6.394297786907
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)
log2(9/180*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: BRD4 [Title/Abstract] AND ZC3H15 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointBRD4(15443100)-ZC3H15(187367222), # samples:1


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Fusion Gene Breakpoints for BRD4_ZC3H15


check button RNA-seq based exon junction arranged fusion gene breakpoints from 8 resources (TCGA, CCLE, cBioPortal, GenBank, ChimerDB, ChimerKB, ChildHoodFusions, and GTEx). For the expressed sample information, go to Fusion Gene Sample section.
HgeneHchrHbpTgeneTchrTbp
BRD4chr1915443100ZC3H15chr215443100
BRD4chr1915443101ZC3H15chr2187367223
BRD4chr1915332290ZC3H15chr2186502496


check button DNA-seq based exon junction arranged fusion gene breakpoints from dbVar. For the expressed sample information, go to Fusion Gene Sample section.
HgeneHchrHbpTgeneTchrTbpSV type


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Tumorigenic MoA (Mechanism of Action) Scenarios of Fusion Genes for BRD4_ZC3H15


check button To generate these tumorigenic scenario annotations, we implemented a deduction-first, retrieval-later computational framework. The pipeline first applies rule-guided reasoning across ten core mechanistic categories (M1–M10) derived from fusion gene biology to infer candidate mechanisms, tumorigenic scenarios, targeting points, and targeting backgrounds. To ensure empirical accountability, a governed Python workflow retrieves literature candidates via NCBI E-utilities and Europe PMC using tiered searches. Using JSON Schema-constrained LLM evidence judges (GPT-5.6 Luna and Terra), retrieved articles are evaluated for specificity and confidence without de novo PMID generation. This produces two distinct versions: a strict version restricted to high- or medium-confidence fusion-specific evidence, and an extended version incorporating broader gene-, pathway-, and contextual evidence.
* We have 10 tumorigenic mechanism categories of fusion genes as shown below.
Constitutively Active Kinases, Catalytic Domain Dysregulation, & Transmembrane Ligand FusionsAberrant Chimeric Transcription Factor / Fusion Transcription Factor ActivityEpigenetic Reprogramming / Histone Modifier DysregulationChromatin Remodeling DysregulationCondensate-Driven Transcriptional Rewiring / LLPPromoter / Enhancer HijackingDominant-Negative AntagonismCell Cycle / Checkpoint Bypass / RNA Processing DysregulationSubcellular Mislocalization / Spatial DysregulationNuclear Body / Sub-organellar Architecture Disruption & Differentiation Blockade

* Strict version: Restricted to high- or medium-confidence fusion-specific evidence.
Fusion Gene NameMechanism CategoryMechanism PubMedTumorigenic ScenariosTumorigenic Scenario PubMedTargeting PointsTargeting PubMedMechanism BackgroundMechanism Background PubMed
BRD4-ZC3H15
Epigenetic Reprogramming / Histone Modifier Dysregulation
M3
BRD4 super-enhancer reader domain couples to ZC3H15 (LSm-5), linking transcriptional elongation to RNA processing and survival.BET bromodomain inhibitors (JQ1, birabresib); CDK9 inhibitorsHyperproliferative epithelial carcinomas

* Extended version: Includes all strict-level fusion evidence plus broader gene-, pathway-, and low-confidence contextual evidence.
Fusion Gene NameMechanism CategoryMechanism PubMedTumorigenic ScenariosTumorigenic Scenario PubMedTargeting PointsTargeting PubMedMechanism BackgroundMechanism Background PubMed
BRD4-ZC3H15
Epigenetic Reprogramming / Histone Modifier Dysregulation
BRD4 super-enhancer reader domain couples to ZC3H15 (LSm-5), linking transcriptional elongation to RNA processing and survival.Evidence level: Limited indirect gene evidence; Confidence: Low; PMID: 35027542; Title: ZC3H15 promotes glioblastoma progression through regulating EGFR stability.; PMID: 35064102; Title: ZC3H15 promotes gastric cancer progression by targeting the FBXW7/c-Myc pathway.BET bromodomain inhibitors (JQ1, birabresib); CDK9 inhibitorsHyperproliferative epithelial carcinomasEvidence level: Limited indirect gene evidence; Confidence: Low; PMID: 35064102; Title: ZC3H15 promotes gastric cancer progression by targeting the FBXW7/c-Myc pathway.

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
BRD4

O60885

.

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneBRD4

GO:0032968

positive regulation of transcription elongation by RNA polymerase II

19103749

HgeneBRD4

GO:0043123

positive regulation of canonical NF-kappaB signal transduction

19103749

HgeneBRD4

GO:0045944

positive regulation of transcription by RNA polymerase II

23086925|23317504|24360279

HgeneBRD4

GO:0050727

regulation of inflammatory response

19103749

TgeneZC3H15

GO:0043547

positive regulation of GTPase activity

23711155


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Fusion Genomic Features for BRD4_ZC3H15


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence) of In-frame fusion genes. 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.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)
BRD4chr1915443100-ZC3H15chr2187367222+2.66e-121.00e+00


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence) of 5UTR-3CSD fusion genes (N-truncated cases).
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)
BRD4chr1915443100-ZC3H15chr2187367222+2.66e-121.00e+00

check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence) of 5CDS-3UTR fusion genes (C-truncated cases).
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonDistribution of six genomic regulatory feature tracks across a ±5 kb window centered on the fusion breakpoints. We input the breakpoint sequences into AlphaGenome and obtained predicted genome tracks at single-base-pair resolution for each modality by running a single forward pass over the reference sequence. Specifically, for each breakpoint, AlphaGenome processed and returned predicted track data across diverse modalities, which were then averaged across all tracks within each output type and visualized across the ±5 kb window. The left panel shows the 5'-gene breakpoint ±5 kb area, and the right panel shows the 3'-gene breakpoint area, with tracks grouped by category: chromatin accessibility (DNase-seq, ATAC-seq), active transcription (RNA-seq, CAGE), and chromatin binding (ChIP-Histone, ChIP-TF).

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Fusion Gene ORF Annotations for BRD4_ZC3H15

check button 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.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5UTR-3CDSENST00000360016ENST00000337859BRD4chr19

15443100

-ZC3H15chr2

187367222

+
5UTR-3UTRENST00000360016ENST00000468120BRD4chr19

15443100

-ZC3H15chr2

187367222

+

check buttonORFfinder Result Based On The Fusion Transcript Sequences of the In-frame Fusion Genes.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(peptide)

check buttonORFfinder Result Based On The Fusion Transcript Sequences of the 5UTR-3CDS Fusion Genes for N-Truncated Protein Search.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(peptide)
ENST00000360016ENST00000337859BRD4chr1915443100ZC3H15chr21873672220884

check buttonORFfinder Result Based On The Fusion Transcript Sequences of the 5CDS-3UTR Fusion Genes for C-Truncated Protein Search.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(peptide)

check buttonDeepORF 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.
HenstTenstHgeneHchrHbpTgeneTchrTbpNo-coding scoreCoding score

check buttonDeepORF Prediction of The Coding Potential Based on The Fusion Transcript Sequence of 5UTR-3CDS Fusion Genes (Potential N-Truncated Proteins).
HenstTenstHgeneHchrHbpTgeneTchrTbpNo-coding scoreCoding score
ENST00000360016ENST00000337859BRD4chr1915443100ZC3H15chr21873672220.00e+001.51e-03

check buttonDeepORF Prediction of The Coding Potential Based on The Fusion Transcript Sequence of 5CDS-3UTR Fusion Genes (Potential C-Truncated Proteins).
HenstTenstHgeneHchrHbpTgeneTchrTbpNo-coding scoreCoding score

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Fusion Protein Retained/Non-Retained Functional Features for BRD4_ZC3H15

check buttonProtein Level Annotation from FGviewer
* 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 download page. Minus value of BPloci means that the break pointn is located before the CDS.
fgviewer annotation
- In-frame and retained protein feature among the 13 regional features (visualization across fusion protein length).
No matching images found for ${hg}_${tg}.

- In-frame and retained protein feature among the 13 regional features (texts).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


check button - Retained PPIs in in-frame fusion.
PartnerHgeneHbpTgeneTbpENSTUniProtStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerHgeneHbpTgeneTbpENSTUniProtStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Fusion Transcript Sequence for BRD4_ZC3H15

check button In-frame Fusion Transcript Sequences.

check button N-Truncated Transcript (5UTR-3CDS) Sequences
>BRD4_ZC3H15_ENST00000360016_ENST00000337859_15443100_187367222 length=1469nt
Breakpoint=0nt
ATACTATGGATAATTGGGATGAGAAAAAGCTGGAAGAAGTAGTGAACAAGAAGCACGGTGAGGCGGAAAAGAAAAAACCAAAAACTCAAATAGTGTGCAAGCATTTCCTGGAAGCTATTGAAAACAACAAGTATGGCTGGTTTTGGGTAT
GCCCTGGAGGGGGTGATATTTGCATGTATCGTCATGCACTTCCTCCTGGATTTGTGTTGAAAAAAGATAAAAAGAAAGAAGAGAAAGAAGATGAAATTTCATTAGAAGATCTAATTGAGAGAGAGCGTTCTGCCCTAGGTCCAAATGTTA
CCAAAATCACTCTAGAATCTTTTCTTGCCTGGAAGAAAAGGAAAAGACAAGAAAAGATTGATAAACTTGAACAAGATATGGAAAGAAGGAAAGCTGACTTCAAAGCAGGGAAAGCACTAGTGATCAGTGGTCGTGAAGTGTTTGAATTTC
GTCCTGAACTGGTCAATGATGATGATGAGGAAGCAGATGATACCCGCTACACCCAGGGAACAGGTGGTGATGAGGTTGATGATTCAGTGAGTGTAAATGACATAGATTTAAGCCTGTACATCCCAAGAGATGTAGATGAAACAGGTATTA
CTGTAGCCAGTCTTGAAAGATTCAGCACATATACTTCAGATAAAGATGAAAACAAATTAAGTGAAGCTTCTGGAGGTAGGGCTGAAAATGGTGAAAGAAGTGACTTGGAAGAGGACAACGAGAGGGAGGGAACGGAAAATGGAGCCATTG
ATGCTGTTCCTGTTGATGAAAATCTTTTCACTGGAGAGGATTTGGATGAACTAGAAGAAGAATTAAATACACTTGATTTAGAAGAATGACACCAAACACATCGCTGAAAAAATTAAGTCAGCTCAGCACGAGTTGAAATTGACTACATTA
ATTTCTTTCCACCTAGAATCAACAGGATGTTTATTTCCTATGCTGATTCTGGAGGAGTTAACCTCCTGCAAAAAAGGCATCTTGTCCCTACATCTTCTCTTCTGACTTTGGCTACATCTCATAGTAAGTTCAGAGTAGTTCATGATAAAT
TGAAAATATAATGGTCATTGCAGAAAATGATTGATGTTGTAACTGTCCACCCAAGTAAGAAGTGTATCTGCCTTTCCATCTTTTGGTTTTCATTTGGGCATGTGCTATTACCAGAAACAACAAACTTATATTTAAAATACCCTTCATTTG
ACACAGTTTTTAATGAGTGATTTAATTTCCTCTGTATTTGTATGTTTAGAAGACTGCCTAAAACATGAGCACTGTACTTCATAAAGGAAACTGCGTATGCAGATTCAGTATTGTGTATCTTTGGACAATTAGATGGACATTTAAAATGGA
ACTTCTTTTATCTGACAGGATCAGCTACAATGCCCTGTGTTAAATTGTTTAAAAGTTTCCCTTTTCTTTTTTGCCAATAAAGTTGTAAATAAAGACCATCATACATTAAAATCCAAATA


check button C-Truncated Transcript (5CDS-3UTR) Sequences

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Fusion Protein Sequence for BRD4_ZC3H15

check button In-frame Fusion Protein Sequences.

check button N-Truncated Protein (5UTR-3CDS) Sequences
>BRD4_ZC3H15_ENST00000360016_ENST00000337859_15443100_187367222 length=884nt
MPMEAIEKMASLCMRDPDEDEEEGTDEDDLEADDDLLAELNEVLGEEQKASETPPPVAQPKPEAPHPGLETTLQERLALYQTAIESARQAGDSAKMRRYDRGLKTLENLLASIRKGNAIDEADIPPPVAIGKGPASTPTYSPAPTQPAPR
IASAPEPRVTLEGPSATAPASSPGLAKPQMPPGPCSPGPLAQLQSRQRDYKLAALHAKQQGDTTAAARHFRVAKSFDAVLEALSRGEPVDLSCLPPPPDQLPPDPPSPPSQPPTPATAPSTTEVPPPPRTLLEALEQRMERYQVAAAQAK
SKGDQRKARMHERIVKQYQDAIRAHKAGRAVDVAELPVPPGFPPIQGLEATKPTQQSLVGVLETAMKLANQDEGPEDEEDEVPKKQNSPVAPTAQPKAPPSRTPQSGSAPTAKAPPKATSTRAQQQLAFLEGRKKQLLQAALRAKQKNDV
EGAKMHLRQAKGLEPMLEASRNGLPVDITKVPPAPVNKDDFALVQRPGPGLSQEAARRYGELTKLIRQQHEMCLNHSNQFTQLGNITETTKFEKLAEDCKRSMDILKQAFVRGLPTPTARFEQRTFSVIKIFPDLSSNDMLLFIVKGINL
PTPPGLSPGDLDVFVRFDFPYPNVEEAQKDKTSVIKNTDSPEFKEQFKLCINRSHRGFRRAIQTKGIKFEVVHKGGLFKTDRVLGTAQLKLDALEIACEVREILEVLDGRRPTGGRLEVMVRIREPLTAQQLETTTERWLVIDPVPAAVP
TQVAGPKGKAPPVPAPARESGNRSARPLHSLSVLAFDQERLERKILALRQARRPVPPEVAQQYQDIMQRSQWQRAQLEQGGVGIRREYAAQLERQLQFYTEAARRLGNDGSRDAAKEALYRRNLVESELQRLRR


check button C-Truncated Protein (5CDS-3UTR) Sequences

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Personalized Fusion Protein Sequence for BRD4_ZC3H15


check button TCGA Kinase/DNA-binding Domain Mutated Fusion Protein Sequences
NumGene GroupDomain LociFusion Protein IDFusion Gene NamePartnerMutated Residue in WT ProteinSeq. LengthMutated Residue in Fusion Protein

check button CCLE Kinase/DNA-binding Domain Mutated Fusion Protein Sequences

NumGene GroupDomain LociFusion Protein IDFusion Gene NamePartnerMutated Residue in WT ProteinSeq. LengthMutated Residue in Fusion Protein

check button TCGA All Mutated Fusion Protein Sequences


Fusion Protein IDSample IDMutated PartnerAAchange in WTSeq. LengthAAchange in Fusion

check button CCLE All Mutated Fusion Protein Sequences


Fusion Protein IDSample IDMutated PartnerAAchange in WTSeq. LengthAAchange in Fusion

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Fusion Gene Exprssed Samples for BRD4_ZC3H15


check buttonRNA-seq based fusion gene expressed samples.
SourceStudyDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDBSTADTCGA-HU-A4GH-01ABRD4

chr19

15442647-ZC3H15

chr2

0

+
ChimerDBSTADTCGA-HU-A4GH-01ABRD4

chr19

15443100-ZC3H15

chr2

15443100

+
WashUSTADTCGA-HU-A4GH-01ABRD4

chr19

15443101-ZC3H15

chr2

187367223

+
cBioPortalSTAD_TCGA_PAN_CAN_ATLAS_2018STADTCGA-HU-A4GH-01BRD4

chr19

15332290ZC3H15

chr2

186502496


check buttonDNA-seq based fusion gene expressed samples.
SourceStudyDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrandSV type


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Related Drugs for BRD4_ZC3H15


check button PubMed Abstract Search With ['A-B' AND 'drug'], ['A::B' AND 'drug']
* For more details on the Studied, Reported, Approved Drugs targeting this fusion gene, Go to FusionPub.
PMIDFusion Gene NameDrugStudy Title

check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status