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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:ITCH-THAP4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ITCH-THAP4
FusionPDB ID: 40369
FusionGDB2.0 ID: 40369
HgeneTgene
Gene symbol

ITCH

THAP4

Gene ID

83737

51078

Gene nameitchy E3 ubiquitin protein ligaseTHAP domain containing 4
SynonymsADMFD|AIF4|AIP4|NAPP1CGI-36|Nb(III)|PP238
Cytomap

20q11.22

2q37.3

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase Itchy homologHECT-type E3 ubiquitin transferase Itchy homologNFE2-associated polypeptide 1atrophin-1 interacting protein 4itchy E3 ubiquitin protein ligase homologTHAP domain-containing protein 4epididymis secretory sperm binding proteinnitrobindin
Modification date2020032920200313
UniProtAcc

Q96J02

Main function of 5'-partner protein: FUNCTION: Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:14602072, PubMed:17028573, PubMed:16387660, PubMed:18718448, PubMed:18718449, PubMed:11046148, PubMed:19592251, PubMed:19116316, PubMed:19881509, PubMed:20491914, PubMed:20392206, PubMed:20068034, PubMed:23146885, PubMed:24790097, PubMed:25631046). Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (PubMed:17028573, PubMed:18718448, PubMed:19131965, PubMed:19881509). Involved in the control of inflammatory signaling pathways (PubMed:19131965). Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways (PubMed:19131965). Promotes the association of the complex after TNF stimulation (PubMed:19131965). Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:19131965). This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1 (PubMed:19131965). Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways (PubMed:19592251). Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response (PubMed:18718448, PubMed:20491914). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages (PubMed:18718448). Mediates JUN ubiquitination and degradation (By similarity). Mediates JUNB ubiquitination and degradation (PubMed:16387660). Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (By similarity). Involved in the negative regulation of MAVS-dependent cellular antiviral responses (PubMed:19881509). Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation (PubMed:19881509). Following ligand stimulation, regulates sorting of Wnt receptor FZD4 to the degradative endocytic pathway probably by modulating PI42KA activity (PubMed:23146885). Ubiquitinates PI4K2A and negatively regulates its catalytic activity (PubMed:23146885). Ubiquitinates chemokine receptor CXCR4 and regulates sorting of CXCR4 to the degradative endocytic pathway following ligand stimulation by ubiquitinating endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:14602072, PubMed:23146885). Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination (PubMed:17028573, PubMed:18628966, PubMed:23886940). Ubiquitinates SNX9 (PubMed:20491914). Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (By similarity). Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP (PubMed:20068034). Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID (PubMed:20392206). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Inhibits the replication of influenza A virus (IAV) via ubiquitination of IAV matrix protein 1 (M1) through 'Lys-48'-linked conjugation resulting in M1 proteasomal degradation (PubMed:30328013). {ECO:0000250|UniProtKB:Q8C863, ECO:0000269|PubMed:14602072, ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:17028573, ECO:0000269|PubMed:18628966, ECO:0000269|PubMed:18718448, ECO:0000269|PubMed:18718449, ECO:0000269|PubMed:19116316, ECO:0000269|PubMed:19131965, ECO:0000269|PubMed:19592251, ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:20068034, ECO:0000269|PubMed:20392206, ECO:0000269|PubMed:20491914, ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:23886940, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:30328013}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000262650, ENST00000374864, 
ENST00000535650, ENST00000483727, 
ENST00000497486, ENST00000402136, 
ENST00000402545, ENST00000407315, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score27 X 16 X 18=777610 X 4 X 8=320
# samples 4411
** MAII scorelog2(44/7776*10)=-4.14345279008112
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/320*10)=-1.5405683813627
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ITCH [Title/Abstract] AND THAP4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ITCH [Title/Abstract] AND THAP4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ITCH(32981687)-THAP4(242545888), # samples:1
Anticipated loss of major functional domain due to fusion event.ITCH-THAP4 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.
ITCH-THAP4 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.
ITCH-THAP4 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.
ITCH-THAP4 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
HgeneITCH

GO:0006511

ubiquitin-dependent protein catabolic process

15678106

HgeneITCH

GO:0016567

protein ubiquitination

17592138|25631046

HgeneITCH

GO:0035519

protein K29-linked ubiquitination

17028573|18628966

HgeneITCH

GO:0070534

protein K63-linked ubiquitination

18718448|19592251

HgeneITCH

GO:0070936

protein K48-linked ubiquitination

19881509



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/chr20:32981687/chr2:242545888)
- 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 ITCH (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 THAP4 (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)
ENST00000374864ITCHchr2032981687+ENST00000402136THAP4chr2242545888-978283213776187
ENST00000374864ITCHchr2032981687+ENST00000407315THAP4chr2242545888-978283213776187
ENST00000374864ITCHchr2032981687+ENST00000402545THAP4chr2242545888-1037283213857214
ENST00000262650ITCHchr2032981687+ENST00000402136THAP4chr2242545888-901206136699187
ENST00000262650ITCHchr2032981687+ENST00000407315THAP4chr2242545888-901206136699187
ENST00000262650ITCHchr2032981687+ENST00000402545THAP4chr2242545888-960206136780214

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
ENST00000374864ENST00000402136ITCHchr2032981687+THAP4chr2242545888-0.044466910.9555331
ENST00000374864ENST00000407315ITCHchr2032981687+THAP4chr2242545888-0.044466910.9555331
ENST00000374864ENST00000402545ITCHchr2032981687+THAP4chr2242545888-0.161525790.83847415
ENST00000262650ENST00000402136ITCHchr2032981687+THAP4chr2242545888-0.040212650.95978737
ENST00000262650ENST00000407315ITCHchr2032981687+THAP4chr2242545888-0.040212650.95978737
ENST00000262650ENST00000402545ITCHchr2032981687+THAP4chr2242545888-0.15117770.8488223

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 ITCH-THAP4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ITCHchr2032981687THAP4chr224254588820623MGSLTMKSQLQITEPPKMNPVVEPLS
ITCHchr2032981687THAP4chr224254588828323MGSLTMKSQLQITEPPKMNPVVEPLS

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Potential FusionNeoAntigen Information of ITCH-THAP4 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.
ITCH-THAP4_32981687_242545888.msa

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)
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:01LQITEPPKM0.9970.9521918
ITCH-THAP4chr2032981687chr2242545888206HLA-B48:01LQITEPPKM0.96570.7815918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:25LQITEPPKM0.90830.9709918
ITCH-THAP4chr2032981687chr2242545888206HLA-B13:02LQITEPPKM0.81970.8354918
ITCH-THAP4chr2032981687chr2242545888206HLA-B13:01LQITEPPKM0.79940.9929918
ITCH-THAP4chr2032981687chr2242545888206HLA-A02:21LQITEPPKM0.76210.6712918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:18LQITEPPKM0.75130.8685918
ITCH-THAP4chr2032981687chr2242545888206HLA-B47:01LQITEPPKM0.74690.7017918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:03LQITEPPKM0.74580.9065918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:10LQITEPPKM0.50790.7358918
ITCH-THAP4chr2032981687chr2242545888206HLA-B39:13LQITEPPKM0.41930.9722918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:37LQITEPPKM0.36210.7144918
ITCH-THAP4chr2032981687chr2242545888206HLA-B52:01LQITEPPKM0.10770.9955918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:07LQITEPPKM0.9870.8595918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:04LQITEPPKM0.97170.964918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:21LQITEPPKM0.90840.9623918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:05LQITEPPKM0.83460.9504918
ITCH-THAP4chr2032981687chr2242545888206HLA-B48:03LQITEPPKM0.76320.643918
ITCH-THAP4chr2032981687chr2242545888206HLA-B39:08LQITEPPKM0.40390.9396918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:135LQITEPPKM0.99710.954918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:27LQITEPPKM0.99710.9599918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:125LQITEPPKM0.9970.9521918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:33LQITEPPKM0.9970.9521918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:34LQITEPPKM0.9970.9521918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:24LQITEPPKM0.99590.9699918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:50LQITEPPKM0.99560.9473918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:35LQITEPPKM0.9840.9466918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:53LQITEPPKM0.9730.9447918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:12LQITEPPKM0.95890.9559918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:73LQITEPPKM0.91760.983918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:39LQITEPPKM0.89530.9324918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:68LQITEPPKM0.87120.8074918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:54LQITEPPKM0.86530.9328918
ITCH-THAP4chr2032981687chr2242545888206HLA-B40:21LQITEPPKM0.84330.7591918
ITCH-THAP4chr2032981687chr2242545888206HLA-B40:49LQITEPPKM0.83540.5161918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:20LQITEPPKM0.81090.9717918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:30LQITEPPKM0.80880.9644918
ITCH-THAP4chr2032981687chr2242545888206HLA-B35:28LQITEPPKM0.80840.9749918
ITCH-THAP4chr2032981687chr2242545888206HLA-A02:14LQITEPPKM0.76580.6237918
ITCH-THAP4chr2032981687chr2242545888206HLA-B40:12LQITEPPKM0.76320.643918
ITCH-THAP4chr2032981687chr2242545888206HLA-A02:06LQITEPPKM0.76210.6712918
ITCH-THAP4chr2032981687chr2242545888206HLA-B35:20LQITEPPKM0.75890.9769918
ITCH-THAP4chr2032981687chr2242545888206HLA-B48:02LQITEPPKM0.65440.9664918
ITCH-THAP4chr2032981687chr2242545888206HLA-B39:02LQITEPPKM0.59850.9721918
ITCH-THAP4chr2032981687chr2242545888206HLA-B15:09LQITEPPKM0.12470.9704918

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Potential FusionNeoAntigen Information of ITCH-THAP4 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 ITCH-THAP4

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.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
4610KSQLQITEPPKMNPITCHTHAP4chr2032981687chr2242545888206

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ITCH-THAP4

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
HLA-B52:013W394610KSQLQITEPPKMNP-6.65674-6.65674
HLA-B44:053DX84610KSQLQITEPPKMNP-6.36866-6.36866

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Vaccine Design for the FusionNeoAntigens of ITCH-THAP4

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
ITCH-THAP4chr2032981687chr2242545888918LQITEPPKMTTCAGATCACTGAGCCCCCCAAGATGA

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 ITCH-THAP4

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
STADITCH-THAP4chr2032981687ENST00000262650chr2242545888ENST00000402136TCGA-BR-7901

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Potential target of CAR-T therapy development for ITCH-THAP4

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 ITCH-THAP4

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 ITCH-THAP4

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