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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:THRA-B4GALNT2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: THRA-B4GALNT2
FusionPDB ID: 90693
FusionGDB2.0 ID: 90693
HgeneTgene
Gene symbol

THRA

B4GALNT2

Gene ID

7067

124872

Gene namethyroid hormone receptor alphabeta-1,4-N-acetyl-galactosaminyltransferase 2
SynonymsAR7|CHNG6|EAR7|ERB-T-1|ERBA|ERBA1|NR1A1|THRA1|THRA2|c-ERBA-1B4GALT|GALGT2
Cytomap

17q21.1

17q21.32

Type of geneprotein-codingprotein-coding
Descriptionthyroid hormone receptor alphaEAR-7ERBA-related 7V-erbA-related protein 7c-erbA-alphanuclear receptor subfamily 1 group A member 1thyroid hormone receptor alpha 1thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homobeta-1,4 N-acetylgalactosaminyltransferase 2UDP-GalNAc:Neu5Aca2-3Galb-R b1,4-N-acetylgalactosaminyltransferaseUDP-GalNAc:Neu5Acalpha2-3Galbeta-R beta1,4-N-acetylgalactosaminyltransferasebeta 1,4 N-acetylgalactosaminyltransferase/betal,4 GalNAcT/Sda-Gal
Modification date2020031320200313
UniProtAcc.

Q8NHY0

Main function of 5'-partner protein: FUNCTION: Involved in the synthesis of the Sd(a) antigen (Sia-alpha2,3-[GalNAc-beta1,4]Gal-beta1,4-GlcNAc), a carbohydrate determinant expressed on erythrocytes, the colonic mucosa and other tissues. Transfers a beta-1,4-linked GalNAc to the galactose residue of an alpha-2,3-sialylated chain. {ECO:0000269|PubMed:12678917, ECO:0000269|PubMed:14688233}.
Ensembl transtripts involved in fusion geneENST idsENST00000264637, ENST00000394121, 
ENST00000450525, ENST00000546243, 
ENST00000584985, 		ENST00000300404, 
ENST00000393354, ENST00000504681, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 10 X 10=140010 X 6 X 3=180
# samples 2312
** MAII scorelog2(23/1400*10)=-2.60572106088795
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(12/180*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: THRA [Title/Abstract] AND B4GALNT2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: THRA [Title/Abstract] AND B4GALNT2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)THRA(38233861)-B4GALNT2(47236399), # samples:3
Anticipated loss of major functional domain due to fusion event.THRA-B4GALNT2 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.
THRA-B4GALNT2 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.
THRA-B4GALNT2 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.
THRA-B4GALNT2 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)

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

GO:0006357

regulation of transcription by RNA polymerase II

18052923

HgeneTHRA

GO:0006366

transcription by RNA polymerase II

8710870|9653119

HgeneTHRA

GO:0009755

hormone-mediated signaling pathway

18052923

HgeneTHRA

GO:0017055

negative regulation of RNA polymerase II transcriptional preinitiation complex assembly

8524305

HgeneTHRA

GO:0045892

negative regulation of transcription, DNA-templated

8710870

HgeneTHRA

GO:2000143

negative regulation of DNA-templated transcription, initiation

8524305

TgeneB4GALNT2

GO:0019276

UDP-N-acetylgalactosamine metabolic process

12678917|14688233

TgeneB4GALNT2

GO:0022408

negative regulation of cell-cell adhesion

16024623



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:38233861/chr17:47236399)
- 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.
FGviewer

check buttonRetention analysis results 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, are available here.

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

check buttonFusion gene breakpoints across B4GALNT2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)
ENST00000394121THRAchr1738233861+ENST00000504681B4GALNT2chr1747236399+20627785561800414
ENST00000394121THRAchr1738233861+ENST00000393354B4GALNT2chr1747236399+19477785561800414
ENST00000394121THRAchr1738233861+ENST00000300404B4GALNT2chr1747236399+19477785561800414
ENST00000264637THRAchr1738233861+ENST00000504681B4GALNT2chr1747236399+20868025801824414
ENST00000264637THRAchr1738233861+ENST00000393354B4GALNT2chr1747236399+19718025801824414
ENST00000264637THRAchr1738233861+ENST00000300404B4GALNT2chr1747236399+19718025801824414
ENST00000584985THRAchr1738233861+ENST00000504681B4GALNT2chr1747236399+20868025801824414
ENST00000584985THRAchr1738233861+ENST00000393354B4GALNT2chr1747236399+19718025801824414
ENST00000584985THRAchr1738233861+ENST00000300404B4GALNT2chr1747236399+19718025801824414
ENST00000450525THRAchr1738233861+ENST00000504681B4GALNT2chr1747236399+19977134911735414
ENST00000450525THRAchr1738233861+ENST00000393354B4GALNT2chr1747236399+18827134911735414
ENST00000450525THRAchr1738233861+ENST00000300404B4GALNT2chr1747236399+18827134911735414
ENST00000546243THRAchr1738233861+ENST00000504681B4GALNT2chr1747236399+19086244021646414
ENST00000546243THRAchr1738233861+ENST00000393354B4GALNT2chr1747236399+17936244021646414
ENST00000546243THRAchr1738233861+ENST00000300404B4GALNT2chr1747236399+17936244021646414
ENST00000394121THRAchr1738233861+ENST00000504681B4GALNT2chr1747236398+20627785561800414
ENST00000394121THRAchr1738233861+ENST00000393354B4GALNT2chr1747236398+19477785561800414
ENST00000394121THRAchr1738233861+ENST00000300404B4GALNT2chr1747236398+19477785561800414
ENST00000264637THRAchr1738233861+ENST00000504681B4GALNT2chr1747236398+20868025801824414
ENST00000264637THRAchr1738233861+ENST00000393354B4GALNT2chr1747236398+19718025801824414
ENST00000264637THRAchr1738233861+ENST00000300404B4GALNT2chr1747236398+19718025801824414
ENST00000584985THRAchr1738233861+ENST00000504681B4GALNT2chr1747236398+20868025801824414
ENST00000584985THRAchr1738233861+ENST00000393354B4GALNT2chr1747236398+19718025801824414
ENST00000584985THRAchr1738233861+ENST00000300404B4GALNT2chr1747236398+19718025801824414
ENST00000450525THRAchr1738233861+ENST00000504681B4GALNT2chr1747236398+19977134911735414
ENST00000450525THRAchr1738233861+ENST00000393354B4GALNT2chr1747236398+18827134911735414
ENST00000450525THRAchr1738233861+ENST00000300404B4GALNT2chr1747236398+18827134911735414
ENST00000546243THRAchr1738233861+ENST00000504681B4GALNT2chr1747236398+19086244021646414
ENST00000546243THRAchr1738233861+ENST00000393354B4GALNT2chr1747236398+17936244021646414
ENST00000546243THRAchr1738233861+ENST00000300404B4GALNT2chr1747236398+17936244021646414

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.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000394121ENST00000504681THRAchr1738233861+B4GALNT2chr1747236399+0.0037549790.99624497
ENST00000394121ENST00000393354THRAchr1738233861+B4GALNT2chr1747236399+0.0036484680.9963515
ENST00000394121ENST00000300404THRAchr1738233861+B4GALNT2chr1747236399+0.0036484680.9963515
ENST00000264637ENST00000504681THRAchr1738233861+B4GALNT2chr1747236399+0.004981970.995018
ENST00000264637ENST00000393354THRAchr1738233861+B4GALNT2chr1747236399+0.0049838210.99501616
ENST00000264637ENST00000300404THRAchr1738233861+B4GALNT2chr1747236399+0.0049838210.99501616
ENST00000584985ENST00000504681THRAchr1738233861+B4GALNT2chr1747236399+0.004981970.995018
ENST00000584985ENST00000393354THRAchr1738233861+B4GALNT2chr1747236399+0.0049838210.99501616
ENST00000584985ENST00000300404THRAchr1738233861+B4GALNT2chr1747236399+0.0049838210.99501616
ENST00000450525ENST00000504681THRAchr1738233861+B4GALNT2chr1747236399+0.0039064450.9960936
ENST00000450525ENST00000393354THRAchr1738233861+B4GALNT2chr1747236399+0.003883990.99611604
ENST00000450525ENST00000300404THRAchr1738233861+B4GALNT2chr1747236399+0.003883990.99611604
ENST00000546243ENST00000504681THRAchr1738233861+B4GALNT2chr1747236399+0.0032261870.9967738
ENST00000546243ENST00000393354THRAchr1738233861+B4GALNT2chr1747236399+0.0031575360.9968425
ENST00000546243ENST00000300404THRAchr1738233861+B4GALNT2chr1747236399+0.0031575360.9968425
ENST00000394121ENST00000504681THRAchr1738233861+B4GALNT2chr1747236398+0.0037549790.99624497
ENST00000394121ENST00000393354THRAchr1738233861+B4GALNT2chr1747236398+0.0036484680.9963515
ENST00000394121ENST00000300404THRAchr1738233861+B4GALNT2chr1747236398+0.0036484680.9963515
ENST00000264637ENST00000504681THRAchr1738233861+B4GALNT2chr1747236398+0.004981970.995018
ENST00000264637ENST00000393354THRAchr1738233861+B4GALNT2chr1747236398+0.0049838210.99501616
ENST00000264637ENST00000300404THRAchr1738233861+B4GALNT2chr1747236398+0.0049838210.99501616
ENST00000584985ENST00000504681THRAchr1738233861+B4GALNT2chr1747236398+0.004981970.995018
ENST00000584985ENST00000393354THRAchr1738233861+B4GALNT2chr1747236398+0.0049838210.99501616
ENST00000584985ENST00000300404THRAchr1738233861+B4GALNT2chr1747236398+0.0049838210.99501616
ENST00000450525ENST00000504681THRAchr1738233861+B4GALNT2chr1747236398+0.0039064450.9960936
ENST00000450525ENST00000393354THRAchr1738233861+B4GALNT2chr1747236398+0.003883990.99611604
ENST00000450525ENST00000300404THRAchr1738233861+B4GALNT2chr1747236398+0.003883990.99611604
ENST00000546243ENST00000504681THRAchr1738233861+B4GALNT2chr1747236398+0.0032261870.9967738
ENST00000546243ENST00000393354THRAchr1738233861+B4GALNT2chr1747236398+0.0031575360.9968425
ENST00000546243ENST00000300404THRAchr1738233861+B4GALNT2chr1747236398+0.0031575360.9968425

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

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for THRA-B4GALNT2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
THRAchr1738233861B4GALNT2chr174723639862474GYHYRCITCEGCKVTLTASLGTLNTL
THRAchr1738233861B4GALNT2chr174723639871374GYHYRCITCEGCKVTLTASLGTLNTL
THRAchr1738233861B4GALNT2chr174723639877874GYHYRCITCEGCKVTLTASLGTLNTL
THRAchr1738233861B4GALNT2chr174723639880274GYHYRCITCEGCKVTLTASLGTLNTL
THRAchr1738233861B4GALNT2chr174723639962474GYHYRCITCEGCKVTLTASLGTLNTL
THRAchr1738233861B4GALNT2chr174723639971374GYHYRCITCEGCKVTLTASLGTLNTL
THRAchr1738233861B4GALNT2chr174723639977874GYHYRCITCEGCKVTLTASLGTLNTL
THRAchr1738233861B4GALNT2chr174723639980274GYHYRCITCEGCKVTLTASLGTLNTL

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Potential FusionNeoAntigen Information of THRA-B4GALNT2 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Potential FusionNeoAntigen Information of THRA-B4GALNT2 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of THRA-B4GALNT2

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of THRA-B4GALNT2

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score

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Vaccine Design for the FusionNeoAntigens of THRA-B4GALNT2

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of THRA-B4GALNT2

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample

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Potential target of CAR-T therapy development for THRA-B4GALNT2

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention 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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to THRA-B4GALNT2

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

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Related Diseases to THRA-B4GALNT2

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

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource