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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:TFEB-SUPT3H

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TFEB-SUPT3H
FusionPDB ID: 90333
FusionGDB2.0 ID: 90333
HgeneTgene
Gene symbol

TFEB

SUPT3H

Gene ID

7942

8464

Gene nametranscription factor EBSPT3 homolog, SAGA and STAGA complex component
SynonymsALPHATFEB|BHLHE35|TCFEBSPT3|SPT3L
Cytomap

6p21.1

6p21.1

Type of geneprotein-codingprotein-coding
Descriptiontranscription factor EBT-cell transcription factor EBclass E basic helix-loop-helix protein 35transcription initiation protein SPT3 homologSPT3-like proteinsuppressor of Ty 3 homolog
Modification date2020032920200313
UniProtAcc

P19484

Main function of 5'-partner protein: FUNCTION: Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22576015, PubMed:22343943, PubMed:22692423, PubMed:30120233, PubMed:31672913). Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF (PubMed:1748288, PubMed:19556463, PubMed:29146937). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:21617040, PubMed:22576015, PubMed:22343943, PubMed:22692423). Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:22576015, PubMed:22343943, PubMed:22692423). Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes (PubMed:19556463, PubMed:22692423). Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy (PubMed:21617040, PubMed:22576015, PubMed:23434374, PubMed:27278822). In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity (By similarity). Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (PubMed:2115126). Plays a role in the signal transduction processes required for normal vascularization of the placenta (By similarity). Involved in the immune response to infection by the bacteria S.aureus or S.enterica, acting downstream of protein kinase D (PKD), probably by regulating cytokine and chemokine expression (By similarity). {ECO:0000250|UniProtKB:Q9R210, ECO:0000269|PubMed:1748288, ECO:0000269|PubMed:19556463, ECO:0000269|PubMed:2115126, ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23434374, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:31672913}.		.
Ensembl transtripts involved in fusion geneENST idsENST00000230323, ENST00000358871, 
ENST00000373033, ENST00000394283, 
ENST00000403298, ENST00000420312, 
ENST00000459689, ENST00000306867, 
ENST00000371458, ENST00000371459, 
ENST00000371460, ENST00000371461, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 11 X 8=105619 X 9 X 9=1539
# samples 1422
** MAII scorelog2(14/1056*10)=-2.91511110241349
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(22/1539*10)=-2.80641780280355
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TFEB [Title/Abstract] AND SUPT3H [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TFEB [Title/Abstract] AND SUPT3H [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TFEB(41657469)-SUPT3H(44797594), # samples:2
Anticipated loss of major functional domain due to fusion event.TFEB-SUPT3H 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.
TFEB-SUPT3H 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.
TFEB-SUPT3H 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.
TFEB-SUPT3H 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.
TFEB-SUPT3H seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
TFEB-SUPT3H seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
TFEB-SUPT3H seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
TFEB-SUPT3H seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
TFEB-SUPT3H seems lost the major protein functional domain in Tgene partner, which is a essential gene 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)

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

GO:0010468

regulation of gene expression

27278822

HgeneTFEB

GO:0045893

positive regulation of transcription, DNA-templated

27278822|29146937

HgeneTFEB

GO:0045944

positive regulation of transcription by RNA polymerase II

19556463

TgeneSUPT3H

GO:0016578

histone deubiquitination

18206972

TgeneSUPT3H

GO:0043966

histone H3 acetylation

11564863



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/chr6:41657469/chr6:44797594)
- 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 TFEB (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 SUPT3H (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)
ENST00000230323TFEBchr641657469-ENST00000371460SUPT3Hchr644797594-197785111671775202
ENST00000230323TFEBchr641657469-ENST00000371459SUPT3Hchr644797594-186485111671775202
ENST00000230323TFEBchr641657469-ENST00000371461SUPT3Hchr644797594-893851302892197
ENST00000230323TFEBchr641657469-ENST00000371458SUPT3Hchr644797594-942851302892196
ENST00000358871TFEBchr641657469-ENST00000371460SUPT3Hchr644797594-181168582726214
ENST00000358871TFEBchr641657469-ENST00000371459SUPT3Hchr644797594-169868582726214
ENST00000358871TFEBchr641657469-ENST00000371461SUPT3Hchr644797594-72768582726215
ENST00000358871TFEBchr641657469-ENST00000371458SUPT3Hchr644797594-77668582726214
ENST00000420312TFEBchr641657469-ENST00000371460SUPT3Hchr644797594-17225969121520202
ENST00000420312TFEBchr641657469-ENST00000371459SUPT3Hchr644797594-16095969121520202
ENST00000420312TFEBchr641657469-ENST00000371461SUPT3Hchr644797594-6385963931131
ENST00000420312TFEBchr641657469-ENST00000371458SUPT3Hchr644797594-687596302637111
ENST00000403298TFEBchr641657469-ENST00000371460SUPT3Hchr644797594-181168582726214
ENST00000403298TFEBchr641657469-ENST00000371459SUPT3Hchr644797594-169868582726214
ENST00000403298TFEBchr641657469-ENST00000371461SUPT3Hchr644797594-72768582726215
ENST00000403298TFEBchr641657469-ENST00000371458SUPT3Hchr644797594-77668582726214
ENST00000394283TFEBchr641657469-ENST00000306867SUPT3Hchr644797594-1818177612271817196
ENST00000230323TFEBchr641657468-ENST00000371460SUPT3Hchr644797594-197785111671775202
ENST00000230323TFEBchr641657468-ENST00000371459SUPT3Hchr644797594-186485111671775202
ENST00000230323TFEBchr641657468-ENST00000371461SUPT3Hchr644797594-893851302892197
ENST00000230323TFEBchr641657468-ENST00000371458SUPT3Hchr644797594-942851302892196
ENST00000358871TFEBchr641657468-ENST00000371460SUPT3Hchr644797594-181168582726214
ENST00000358871TFEBchr641657468-ENST00000371459SUPT3Hchr644797594-169868582726214
ENST00000358871TFEBchr641657468-ENST00000371461SUPT3Hchr644797594-72768582726215
ENST00000358871TFEBchr641657468-ENST00000371458SUPT3Hchr644797594-77668582726214
ENST00000420312TFEBchr641657468-ENST00000371460SUPT3Hchr644797594-17225969121520202
ENST00000420312TFEBchr641657468-ENST00000371459SUPT3Hchr644797594-16095969121520202
ENST00000420312TFEBchr641657468-ENST00000371461SUPT3Hchr644797594-6385963931131
ENST00000420312TFEBchr641657468-ENST00000371458SUPT3Hchr644797594-687596302637111
ENST00000403298TFEBchr641657468-ENST00000371460SUPT3Hchr644797594-181168582726214
ENST00000403298TFEBchr641657468-ENST00000371459SUPT3Hchr644797594-169868582726214
ENST00000403298TFEBchr641657468-ENST00000371461SUPT3Hchr644797594-72768582726215
ENST00000403298TFEBchr641657468-ENST00000371458SUPT3Hchr644797594-77668582726214
ENST00000394283TFEBchr641657468-ENST00000306867SUPT3Hchr644797594-1818177612271817196

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
ENST00000230323ENST00000371460TFEBchr641657469-SUPT3Hchr644797594-0.0012499790.99875
ENST00000230323ENST00000371459TFEBchr641657469-SUPT3Hchr644797594-0.0010870150.99891305
ENST00000230323ENST00000371461TFEBchr641657469-SUPT3Hchr644797594-0.000946940.99905306
ENST00000230323ENST00000371458TFEBchr641657469-SUPT3Hchr644797594-0.0011949150.99880505
ENST00000358871ENST00000371460TFEBchr641657469-SUPT3Hchr644797594-0.0018892830.9981108
ENST00000358871ENST00000371459TFEBchr641657469-SUPT3Hchr644797594-0.0018659190.9981341
ENST00000358871ENST00000371461TFEBchr641657469-SUPT3Hchr644797594-0.0003197680.9996803
ENST00000358871ENST00000371458TFEBchr641657469-SUPT3Hchr644797594-0.0004536710.99954635
ENST00000420312ENST00000371460TFEBchr641657469-SUPT3Hchr644797594-0.0674387440.9325613
ENST00000420312ENST00000371459TFEBchr641657469-SUPT3Hchr644797594-0.0568684080.9431316
ENST00000420312ENST00000371461TFEBchr641657469-SUPT3Hchr644797594-0.0046469840.995353
ENST00000420312ENST00000371458TFEBchr641657469-SUPT3Hchr644797594-0.0055712590.99442875
ENST00000403298ENST00000371460TFEBchr641657469-SUPT3Hchr644797594-0.0018892830.9981108
ENST00000403298ENST00000371459TFEBchr641657469-SUPT3Hchr644797594-0.0018659190.9981341
ENST00000403298ENST00000371461TFEBchr641657469-SUPT3Hchr644797594-0.0003197680.9996803
ENST00000403298ENST00000371458TFEBchr641657469-SUPT3Hchr644797594-0.0004536710.99954635
ENST00000394283ENST00000306867TFEBchr641657469-SUPT3Hchr644797594-0.007181130.9928189
ENST00000230323ENST00000371460TFEBchr641657468-SUPT3Hchr644797594-0.0012499790.99875
ENST00000230323ENST00000371459TFEBchr641657468-SUPT3Hchr644797594-0.0010870150.99891305
ENST00000230323ENST00000371461TFEBchr641657468-SUPT3Hchr644797594-0.000946940.99905306
ENST00000230323ENST00000371458TFEBchr641657468-SUPT3Hchr644797594-0.0011949150.99880505
ENST00000358871ENST00000371460TFEBchr641657468-SUPT3Hchr644797594-0.0018892830.9981108
ENST00000358871ENST00000371459TFEBchr641657468-SUPT3Hchr644797594-0.0018659190.9981341
ENST00000358871ENST00000371461TFEBchr641657468-SUPT3Hchr644797594-0.0003197680.9996803
ENST00000358871ENST00000371458TFEBchr641657468-SUPT3Hchr644797594-0.0004536710.99954635
ENST00000420312ENST00000371460TFEBchr641657468-SUPT3Hchr644797594-0.0674387440.9325613
ENST00000420312ENST00000371459TFEBchr641657468-SUPT3Hchr644797594-0.0568684080.9431316
ENST00000420312ENST00000371461TFEBchr641657468-SUPT3Hchr644797594-0.0046469840.995353
ENST00000420312ENST00000371458TFEBchr641657468-SUPT3Hchr644797594-0.0055712590.99442875
ENST00000403298ENST00000371460TFEBchr641657468-SUPT3Hchr644797594-0.0018892830.9981108
ENST00000403298ENST00000371459TFEBchr641657468-SUPT3Hchr644797594-0.0018659190.9981341
ENST00000403298ENST00000371461TFEBchr641657468-SUPT3Hchr644797594-0.0003197680.9996803
ENST00000403298ENST00000371458TFEBchr641657468-SUPT3Hchr644797594-0.0004536710.99954635
ENST00000394283ENST00000306867TFEBchr641657468-SUPT3Hchr644797594-0.007181130.9928189

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 TFEB-SUPT3H

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide

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Potential FusionNeoAntigen Information of TFEB-SUPT3H 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 TFEB-SUPT3H 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 TFEB-SUPT3H

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 TFEB-SUPT3H

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 TFEB-SUPT3H

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 TFEB-SUPT3H

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 TFEB-SUPT3H

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 TFEB-SUPT3H

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 TFEB-SUPT3H

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
HgeneTFEBC4518356MiT family translocation renal cell carcinoma2ORPHANET