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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:BRD8-HDAC3

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: BRD8-HDAC3
	FusionPDB ID: 10215
	FusionGDB2.0 ID: 10215
		Hgene	Tgene
	Gene symbol	BRD8	HDAC3
	Gene ID	10902	8841
	Gene name	bromodomain containing 8	histone deacetylase 3
	Synonyms	SMAP\|SMAP2\|p120	HD3\|KDAC3\|RPD3\|RPD3-2
	Cytomap	5q31.2	5q31.3
	Type of gene	protein-coding	protein-coding
	Description	bromodomain-containing protein 8skeletal muscle abundant protein 2thyroid hormone receptor coactivating protein of 120 kDatrCP120	histone deacetylase 3SMAP45
	Modification date	20200313	20200329
	UniProtAcc	Q9H0E9	O15379
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000230901, ENST00000254900, ENST00000402931, ENST00000411594, ENST00000455658, ENST00000515014,	ENST00000469207, ENST00000305264,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	5 X 5 X 3=75	3 X 3 X 3=27
	# samples	5	3
	** MAII score	log2(5/75*10)=-0.584962500721156 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(3/27*10)=0.15200309344505 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Context (manual curation of fusion genes in FusionPDB)	PubMed: BRD8 [Title/Abstract] AND HDAC3 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	BRD8(137513260)-HDAC3(141009692), # samples:1
Anticipated loss of major functional domain due to fusion event.	BRD8-HDAC3 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. BRD8-HDAC3 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame 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	BRD8	GO:0043967	histone H4 acetylation	14966270
Hgene	BRD8	GO:0043968	histone H2A acetylation	14966270
Tgene	HDAC3	GO:0000122	negative regulation of transcription by RNA polymerase II	16569215\|18417529\|18854353
Tgene	HDAC3	GO:0001934	positive regulation of protein phosphorylation	25190803
Tgene	HDAC3	GO:0006476	protein deacetylation	17172643\|21030595
Tgene	HDAC3	GO:0031647	regulation of protein stability	25190803
Tgene	HDAC3	GO:0042307	positive regulation of protein import into nucleus	25190803
Tgene	HDAC3	GO:0045944	positive regulation of transcription by RNA polymerase II	25190803
Tgene	HDAC3	GO:0071498	cellular response to fluid shear stress	25190803

Fusion gene breakpoints across BRD8 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across HDAC3 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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Fusion Gene Sample Information

Fusion gene information from FusionGDB2.0.

Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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	STAD	TCGA-CD-8531-01A	BRD8	chr5	137513260	-	HDAC3	chr5	141009692	-

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Fusion ORF Analysis

Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.

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)
ENST00000254900	BRD8	chr5	137513260	-	ENST00000305264	HDAC3	chr5	141009692	-	2086	488	372	1493	373
ENST00000230901	BRD8	chr5	137513260	-	ENST00000305264	HDAC3	chr5	141009692	-	1730	132	16	1137	373
ENST00000402931	BRD8	chr5	137513260	-	ENST00000305264	HDAC3	chr5	141009692	-	1733	135	19	1140	373
ENST00000411594	BRD8	chr5	137513260	-	ENST00000305264	HDAC3	chr5	141009692	-	1769	171	55	1176	373
ENST00000455658	BRD8	chr5	137513260	-	ENST00000305264	HDAC3	chr5	141009692	-	1729	131	15	1136	373

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
ENST00000254900	ENST00000305264	BRD8	chr5	137513260	-	HDAC3	chr5	141009692	-	0.001120593	0.9988794
ENST00000230901	ENST00000305264	BRD8	chr5	137513260	-	HDAC3	chr5	141009692	-	0.001512234	0.9984877
ENST00000402931	ENST00000305264	BRD8	chr5	137513260	-	HDAC3	chr5	141009692	-	0.00150817	0.99849176
ENST00000411594	ENST00000305264	BRD8	chr5	137513260	-	HDAC3	chr5	141009692	-	0.00160637	0.9983936
ENST00000455658	ENST00000305264	BRD8	chr5	137513260	-	HDAC3	chr5	141009692	-	0.001504651	0.99849534

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Fusion Amino Acid Sequences

For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>10215_10215_1_BRD8-HDAC3_BRD8_chr5_137513260_ENST00000230901_HDAC3_chr5_141009692_ENST00000305264_length(amino acids)=373AA_BP=24
MATGTGKHKLLSTGPTEPWSIREKLCLASSVMRSGDQNCPVFPGLFEFCSRYTGASLQGATQLNNKICDIAINWAGGLHHAKKFEASGFC
YVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEAFYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHL
FQPVINQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTVRNVARCWTYETSLLVEEAISEELPY
SEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQTIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYD

--------------------------------------------------------------

>10215_10215_2_BRD8-HDAC3_BRD8_chr5_137513260_ENST00000254900_HDAC3_chr5_141009692_ENST00000305264_length(amino acids)=373AA_BP=24
MATGTGKHKLLSTGPTEPWSIREKLCLASSVMRSGDQNCPVFPGLFEFCSRYTGASLQGATQLNNKICDIAINWAGGLHHAKKFEASGFC
YVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEAFYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHL
FQPVINQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTVRNVARCWTYETSLLVEEAISEELPY
SEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQTIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYD

--------------------------------------------------------------

>10215_10215_3_BRD8-HDAC3_BRD8_chr5_137513260_ENST00000402931_HDAC3_chr5_141009692_ENST00000305264_length(amino acids)=373AA_BP=24
MATGTGKHKLLSTGPTEPWSIREKLCLASSVMRSGDQNCPVFPGLFEFCSRYTGASLQGATQLNNKICDIAINWAGGLHHAKKFEASGFC
YVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEAFYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHL
FQPVINQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTVRNVARCWTYETSLLVEEAISEELPY
SEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQTIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYD

--------------------------------------------------------------

>10215_10215_4_BRD8-HDAC3_BRD8_chr5_137513260_ENST00000411594_HDAC3_chr5_141009692_ENST00000305264_length(amino acids)=373AA_BP=24
MATGTGKHKLLSTGPTEPWSIREKLCLASSVMRSGDQNCPVFPGLFEFCSRYTGASLQGATQLNNKICDIAINWAGGLHHAKKFEASGFC
YVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEAFYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHL
FQPVINQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTVRNVARCWTYETSLLVEEAISEELPY
SEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQTIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYD

--------------------------------------------------------------

>10215_10215_5_BRD8-HDAC3_BRD8_chr5_137513260_ENST00000455658_HDAC3_chr5_141009692_ENST00000305264_length(amino acids)=373AA_BP=24
MATGTGKHKLLSTGPTEPWSIREKLCLASSVMRSGDQNCPVFPGLFEFCSRYTGASLQGATQLNNKICDIAINWAGGLHHAKKFEASGFC
YVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEAFYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHL
FQPVINQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTVRNVARCWTYETSLLVEEAISEELPY
SEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQTIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYD

--------------------------------------------------------------

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Fusion Protein Functional Features

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr5:137513260/chr5:141009692)
- 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
BRD8 Q9H0E9	HDAC3 O15379
FUNCTION: May act as a coactivator during transcriptional activation by hormone-activated nuclear receptors (NR). Isoform 2 stimulates transcriptional activation by AR/DHTR, ESR1/NR3A1, RXRA/NR2B1 and THRB/ERBA2. At least isoform 1 and isoform 2 are components of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. {ECO:0000269\|PubMed:10517671, ECO:0000269\|PubMed:14966270, ECO:0000269\|PubMed:24463511}.	FUNCTION: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression. Probably participates in the regulation of transcription through its binding to the zinc-finger transcription factor YY1; increases YY1 repression activity. Required to repress transcription of the POU1F1 transcription factor. Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (PubMed:21444723, PubMed:23911289). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (By similarity). During the activation phase, promotes the accumulation of ubiquitinated ARNTL/BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and ARNTL/BMAL1 (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). Serves as a corepressor of RARA, causing its deacetylation and inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). Interacts with SETD5 (By similarity). {ECO:0000250\|UniProtKB:O88895, ECO:0000269\|PubMed:21444723, ECO:0000269\|PubMed:23911289, ECO:0000269\|PubMed:25190803, ECO:0000269\|PubMed:28167758}.

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.

- 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

- 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

Hgene

BRD8

chr5:137513260

chr5:141009692

ENST00000230901

97_171

38.666666666666664

952.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

BRD8

chr5:137513260

chr5:141009692

ENST00000254900

97_171

38.666666666666664

1236.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

BRD8

chr5:137513260

chr5:141009692

ENST00000411594

97_171

38.666666666666664

867.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

BRD8

chr5:137513260

chr5:141009692

ENST00000230901

1120_1190

38.666666666666664

952.0

Domain

Bromo 2

Hgene

BRD8

chr5:137513260

chr5:141009692

ENST00000230901

724_794

38.666666666666664

952.0

Domain

Bromo 1

Hgene

BRD8

chr5:137513260

chr5:141009692

ENST00000254900

1120_1190

38.666666666666664

1236.0

Domain

Bromo 2

Hgene

BRD8

chr5:137513260

chr5:141009692

ENST00000254900

724_794

38.666666666666664

1236.0

Domain

Bromo 1

Hgene

BRD8

chr5:137513260

chr5:141009692

ENST00000411594

1120_1190

38.666666666666664

867.0

Domain

Bromo 2

Hgene

BRD8

chr5:137513260

chr5:141009692

ENST00000411594

724_794

38.666666666666664

867.0

Domain

Bromo 1

Tgene

HDAC3

chr5:137513260

chr5:141009692

ENST00000305264

3_316

93.66666666666667

429.0

Region

Note=Histone deacetylase

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Fusion Protein-Protein Interaction

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)

Gene

PPI interactors

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
BRD8
HDAC3

- Retained interactions in fusion protein (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost interactions due to fusion (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs to BRD8-HDAC3

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

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Related Diseases to BRD8-HDAC3

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source