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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:TEAD1-CTR9

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TEAD1-CTR9
FusionPDB ID: 89953
FusionGDB2.0 ID: 89953
HgeneTgene
Gene symbol

TEAD1

CTR9

Gene ID

7003

9646

Gene nameTEA domain transcription factor 1CTR9 homolog, Paf1/RNA polymerase II complex component
SynonymsAA|NTEF-1|REF1|TCF-13|TCF13|TEAD-1|TEF-1SH2BP1|TSBP|p150|p150TSP
Cytomap

11p15.3

11p15.4

Type of geneprotein-codingprotein-coding
Descriptiontranscriptional enhancer factor TEF-1TEA domain family member 1 (SV40 transcriptional enhancer factor)protein GT-IICtranscription factor 13transcriptional enhancer factor 1RNA polymerase-associated protein CTR9 homologCtr9, Paf1/RNA polymerase II complex component, homologSH2 domain binding protein 1 (tetratricopeptide repeat containing)TPR-containing, SH2-binding phosphoprotein
Modification date2020032920200313
UniProtAcc.

Q6PD62

Main function of 5'-partner protein: FUNCTION: Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3) and dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of the SET1 complex. Involved in transcriptional regulation of IL6-responsive genes and in JAK-STAT pathway; may regulate DNA-association of STAT3 (By similarity). {ECO:0000250|UniProtKB:Q62018, ECO:0000269|PubMed:16024656, ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879}.
Ensembl transtripts involved in fusion geneENST idsENST00000361905, ENST00000361985, 
ENST00000526600, ENST00000527636, 
ENST00000334310, ENST00000527575, 
ENST00000361367, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score19 X 11 X 12=25086 X 6 X 4=144
# samples 236
** MAII scorelog2(23/2508*10)=-3.44683158185766
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/144*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TEAD1 [Title/Abstract] AND CTR9 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TEAD1 [Title/Abstract] AND CTR9 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TEAD1(12923660)-CTR9(10784978), # samples:3
Anticipated loss of major functional domain due to fusion event.TEAD1-CTR9 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.
TEAD1-CTR9 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.
TEAD1-CTR9 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.
TEAD1-CTR9 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
HgeneTEAD1

GO:0035329

hippo signaling

18579750|19324877

TgeneCTR9

GO:0010390

histone monoubiquitination

16307923

TgeneCTR9

GO:0019827

stem cell population maintenance

19345177

TgeneCTR9

GO:0032968

positive regulation of transcription elongation from RNA polymerase II promoter

20178742

TgeneCTR9

GO:0033523

histone H2B ubiquitination

16307923

TgeneCTR9

GO:0045638

negative regulation of myeloid cell differentiation

20541477

TgeneCTR9

GO:0045944

positive regulation of transcription by RNA polymerase II

20178742



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/chr11:12923660/chr11:10784978)
- 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 TEAD1 (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 CTR9 (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)
ENST00000361905TEAD1chr1112923660+ENST00000361367CTR9chr1110784978+4804149354241651207
ENST00000527636TEAD1chr1112923660+ENST00000361367CTR9chr1110784978+4635132437339961207
ENST00000361985TEAD1chr1112923660+ENST00000361367CTR9chr1110784978+4338102713336991188
ENST00000526600TEAD1chr1112923660+ENST00000361367CTR9chr1110784978+411980811534801121

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
ENST00000361905ENST00000361367TEAD1chr1112923660+CTR9chr1110784978+0.0018953070.9981047
ENST00000527636ENST00000361367TEAD1chr1112923660+CTR9chr1110784978+0.0015249510.998475
ENST00000361985ENST00000361367TEAD1chr1112923660+CTR9chr1110784978+0.0010433320.9989567
ENST00000526600ENST00000361367TEAD1chr1112923660+CTR9chr1110784978+0.0005545340.9994455

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 TEAD1-CTR9

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TEAD1chr1112923660CTR9chr11107849781027298KGPQNAFFLVKFWDYSKVQHLALHAF
TEAD1chr1112923660CTR9chr11107849781324317KGPQNAFFLVKFWDYSKVQHLALHAF
TEAD1chr1112923660CTR9chr11107849781493317KGPQNAFFLVKFWDYSKVQHLALHAF
TEAD1chr1112923660CTR9chr1110784978808231KGPQNAFFLVKFWDYSKVQHLALHAF

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Potential FusionNeoAntigen Information of TEAD1-CTR9 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.
TEAD1-CTR9_12923660_10784978.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)
TEAD1-CTR9chr1112923660chr11107849781493HLA-B39:13WDYSKVQHL0.6760.77711221
TEAD1-CTR9chr1112923660chr11107849781493HLA-B13:01WDYSKVQHL0.63850.811221
TEAD1-CTR9chr1112923660chr11107849781493HLA-B39:08WDYSKVQHL0.87240.77231221
TEAD1-CTR9chr1112923660chr11107849781493HLA-C04:10FWDYSKVQHL0.99990.87421121
TEAD1-CTR9chr1112923660chr11107849781493HLA-C04:07FWDYSKVQHL0.99980.87641121
TEAD1-CTR9chr1112923660chr11107849781493HLA-C07:29FWDYSKVQHL0.99290.91421121
TEAD1-CTR9chr1112923660chr11107849781493HLA-C07:13FWDYSKVQHL0.99090.88181121
TEAD1-CTR9chr1112923660chr11107849781493HLA-C04:14FWDYSKVQHL0.97770.79451121
TEAD1-CTR9chr1112923660chr11107849781493HLA-B39:02WDYSKVQHL0.84250.77231221
TEAD1-CTR9chr1112923660chr11107849781493HLA-B40:04WDYSKVQHL0.81770.57511221
TEAD1-CTR9chr1112923660chr11107849781493HLA-C18:01FWDYSKVQHL0.99980.86561121
TEAD1-CTR9chr1112923660chr11107849781493HLA-C04:01FWDYSKVQHL0.99980.87641121
TEAD1-CTR9chr1112923660chr11107849781493HLA-C07:04FWDYSKVQHL0.99550.92011121
TEAD1-CTR9chr1112923660chr11107849781493HLA-C04:04FWDYSKVQHL0.99190.8271121

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Potential FusionNeoAntigen Information of TEAD1-CTR9 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 TEAD1-CTR9

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
2364FFLVKFWDYSKVQHTEAD1CTR9chr1112923660chr11107849781493

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TEAD1-CTR9

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-B14:023BVN2364FFLVKFWDYSKVQH-6.6827-6.7945
HLA-B14:023BVN2364FFLVKFWDYSKVQH-1.45212-2.49522
HLA-B52:013W392364FFLVKFWDYSKVQH-6.45613-6.56793
HLA-B52:013W392364FFLVKFWDYSKVQH-3.70581-4.74891
HLA-A11:014UQ22364FFLVKFWDYSKVQH-9.38435-9.49615
HLA-A24:025HGA2364FFLVKFWDYSKVQH-8.10956-8.22136
HLA-A24:025HGA2364FFLVKFWDYSKVQH-6.02437-7.06747
HLA-B27:056PYJ2364FFLVKFWDYSKVQH-5.90005-6.94315
HLA-B44:053DX82364FFLVKFWDYSKVQH-6.67369-7.71679
HLA-B44:053DX82364FFLVKFWDYSKVQH-5.40805-5.51985

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Vaccine Design for the FusionNeoAntigens of TEAD1-CTR9

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
TEAD1-CTR9chr1112923660chr11107849781121FWDYSKVQHLTTCTGGGATTATAGTAAAGTCCAGCATCTG
TEAD1-CTR9chr1112923660chr11107849781221WDYSKVQHLTGGGATTATAGTAAAGTCCAGCATCTG

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 TEAD1-CTR9

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
UCECTEAD1-CTR9chr1112923660ENST00000361905chr1110784978ENST00000361367TCGA-EO-A3KU-01A

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Potential target of CAR-T therapy development for TEAD1-CTR9

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 TEAD1-CTR9

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 TEAD1-CTR9

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