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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:MAML2-YAP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAML2-YAP1
FusionPDB ID: 51014
FusionGDB2.0 ID: 51014
HgeneTgene
Gene symbol

MAML2

YAP1

Gene ID

84441

10413

Gene namemastermind like transcriptional coactivator 2Yes1 associated transcriptional regulator
SynonymsMAM-3|MAM2|MAM3|MLL-MAML2COB1|YAP|YAP2|YAP65|YKI
Cytomap

11q21

11q22.1

Type of geneprotein-codingprotein-coding
Descriptionmastermind-like protein 2mam-2mastermind-like 2transcriptional coactivator YAP165 kDa Yes-associated proteinYes associated protein 1protein yorkie homologyes-associated protein 1yes-associated protein 2yes-associated protein YAP65 homologyorkie homolog
Modification date2020031320200329
UniProtAcc

Q8IZL2

Main function of 5'-partner protein: FUNCTION: Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Potentiates activation by NOTCH3 and NOTCH4 more efficiently than MAML1 or MAML3. {ECO:0000269|PubMed:12370315, ECO:0000269|PubMed:12386158, ECO:0000269|PubMed:12539049}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000524717, ENST00000528834, 
ENST00000282441, ENST00000345877, 
ENST00000524575, ENST00000526343, 
ENST00000531439, ENST00000537274, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 15 X 8=192020 X 10 X 13=2600
# samples 2021
** MAII scorelog2(20/1920*10)=-3.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(21/2600*10)=-3.63005039024969
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MAML2 [Title/Abstract] AND YAP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MAML2 [Title/Abstract] AND YAP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAML2(96074547)-YAP1(102094353), # samples:3
YAP1(102076805)-MAML2(95826681), # samples:3
Anticipated loss of major functional domain due to fusion event.MAML2-YAP1 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.
MAML2-YAP1 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.
MAML2-YAP1 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.
MAML2-YAP1 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.
YAP1-MAML2 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.
YAP1-MAML2 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
HgeneMAML2

GO:0007219

Notch signaling pathway

12370315

HgeneMAML2

GO:0045944

positive regulation of transcription by RNA polymerase II

12370315

TgeneYAP1

GO:0006974

cellular response to DNA damage stimulus

18280240

TgeneYAP1

GO:0008283

cell proliferation

17974916

TgeneYAP1

GO:0032570

response to progesterone

16772533

TgeneYAP1

GO:0033148

positive regulation of intracellular estrogen receptor signaling pathway

16772533

TgeneYAP1

GO:0045893

positive regulation of transcription, DNA-templated

20368466

TgeneYAP1

GO:0045944

positive regulation of transcription by RNA polymerase II

25796446

TgeneYAP1

GO:0050767

regulation of neurogenesis

25433207

TgeneYAP1

GO:0050847

progesterone receptor signaling pathway

16772533

TgeneYAP1

GO:0060242

contact inhibition

17974916

TgeneYAP1

GO:0065003

protein-containing complex assembly

20368466

TgeneYAP1

GO:0071480

cellular response to gamma radiation

18280240

TgeneYAP1

GO:0072091

regulation of stem cell proliferation

25433207



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/chr11:96074547/chr11:102094353)
- 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 MAML2 (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 YAP1 (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)
ENST00000524717MAML2chr1196074547-ENST00000526343YAP1chr11102094353+2933179812852280331
ENST00000524717MAML2chr1196074547-ENST00000282441YAP1chr11102094353+5764179812852280331
ENST00000524717MAML2chr1196074547-ENST00000537274YAP1chr11102094353+5764179812852280331
ENST00000524717MAML2chr1196074547-ENST00000345877YAP1chr11102094353+5764179812852280331
ENST00000524717MAML2chr1196074547-ENST00000531439YAP1chr11102094353+2304179812852280331
ENST00000524717MAML2chr1196074547-ENST00000524575YAP1chr11102094353+2493179812852280331

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
ENST00000524717ENST00000526343MAML2chr1196074547-YAP1chr11102094353+0.0043111540.99568886
ENST00000524717ENST00000282441MAML2chr1196074547-YAP1chr11102094353+0.0005088290.9994911
ENST00000524717ENST00000537274MAML2chr1196074547-YAP1chr11102094353+0.0005088290.9994911
ENST00000524717ENST00000345877MAML2chr1196074547-YAP1chr11102094353+0.0005088290.9994911
ENST00000524717ENST00000531439MAML2chr1196074547-YAP1chr11102094353+0.011307440.9886925
ENST00000524717ENST00000524575MAML2chr1196074547-YAP1chr11102094353+0.0097876740.99021226

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 MAML2-YAP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MAML2chr1196074547YAP1chr111020943531798171STPGDQRNSALIAELALRSQLPTLEQ

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Potential FusionNeoAntigen Information of MAML2-YAP1 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.
MAML2-YAP1_96074547_102094353.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)
MAML2-YAP1chr1196074547chr111020943531798HLA-B13:01AELALRSQL0.99790.98511221
MAML2-YAP1chr1196074547chr111020943531798HLA-B44:03AELALRSQL0.99780.98521221
MAML2-YAP1chr1196074547chr111020943531798HLA-B50:02AELALRSQL0.99630.76261221
MAML2-YAP1chr1196074547chr111020943531798HLA-B48:01AELALRSQL0.99330.50481221
MAML2-YAP1chr1196074547chr111020943531798HLA-B47:01AELALRSQL0.98710.70741221
MAML2-YAP1chr1196074547chr111020943531798HLA-B45:01AELALRSQL0.98380.97911221
MAML2-YAP1chr1196074547chr111020943531798HLA-B35:03SALIAELAL0.96220.8139817
MAML2-YAP1chr1196074547chr111020943531798HLA-A74:03ALIAELALR0.93650.6727918
MAML2-YAP1chr1196074547chr111020943531798HLA-A74:09ALIAELALR0.93650.6727918
MAML2-YAP1chr1196074547chr111020943531798HLA-A74:11ALIAELALR0.93650.6727918
MAML2-YAP1chr1196074547chr111020943531798HLA-A31:02ALIAELALR0.8770.6474918
MAML2-YAP1chr1196074547chr111020943531798HLA-B35:02SALIAELAL0.84050.9578817
MAML2-YAP1chr1196074547chr111020943531798HLA-B35:04SALIAELAL0.84050.9578817
MAML2-YAP1chr1196074547chr111020943531798HLA-B41:01AELALRSQL0.62160.97961221
MAML2-YAP1chr1196074547chr111020943531798HLA-B39:13AELALRSQL0.5650.98261221
MAML2-YAP1chr1196074547chr111020943531798HLA-B50:01AELALRSQL0.39990.80941221
MAML2-YAP1chr1196074547chr111020943531798HLA-B27:04QRNSALIAEL0.99990.7257515
MAML2-YAP1chr1196074547chr111020943531798HLA-B27:05QRNSALIAEL0.99990.7885515
MAML2-YAP1chr1196074547chr111020943531798HLA-B27:07QRNSALIAEL0.99980.5409515
MAML2-YAP1chr1196074547chr111020943531798HLA-B45:01AELALRSQLP0.9960.99181222
MAML2-YAP1chr1196074547chr111020943531798HLA-B50:02AELALRSQLP0.99120.82041222
MAML2-YAP1chr1196074547chr111020943531798HLA-B07:10QRNSALIAEL0.7820.5042515
MAML2-YAP1chr1196074547chr111020943531798HLA-B40:06AELALRSQL0.99960.71771221
MAML2-YAP1chr1196074547chr111020943531798HLA-C03:19SALIAELAL0.99940.9918817
MAML2-YAP1chr1196074547chr111020943531798HLA-B44:10AELALRSQL0.99930.7221221
MAML2-YAP1chr1196074547chr111020943531798HLA-C03:08SALIAELAL0.99920.9414817
MAML2-YAP1chr1196074547chr111020943531798HLA-C03:07SALIAELAL0.99920.9682817
MAML2-YAP1chr1196074547chr111020943531798HLA-B44:09AELALRSQL0.99720.58641221
MAML2-YAP1chr1196074547chr111020943531798HLA-C08:13SALIAELAL0.98090.9692817
MAML2-YAP1chr1196074547chr111020943531798HLA-C08:04SALIAELAL0.98090.9692817
MAML2-YAP1chr1196074547chr111020943531798HLA-C08:03SALIAELAL0.91770.99817
MAML2-YAP1chr1196074547chr111020943531798HLA-B35:12SALIAELAL0.84050.9578817
MAML2-YAP1chr1196074547chr111020943531798HLA-B39:08AELALRSQL0.80670.96141221
MAML2-YAP1chr1196074547chr111020943531798HLA-B27:03QRNSALIAEL0.99660.8095515
MAML2-YAP1chr1196074547chr111020943531798HLA-B73:01QRNSALIAELA0.99740.7611516
MAML2-YAP1chr1196074547chr111020943531798HLA-B40:04AELALRSQL0.99950.80331221
MAML2-YAP1chr1196074547chr111020943531798HLA-C03:03SALIAELAL0.99930.9918817
MAML2-YAP1chr1196074547chr111020943531798HLA-C03:04SALIAELAL0.99930.9918817
MAML2-YAP1chr1196074547chr111020943531798HLA-C03:17SALIAELAL0.99860.9656817
MAML2-YAP1chr1196074547chr111020943531798HLA-C03:05SALIAELAL0.99840.9476817
MAML2-YAP1chr1196074547chr111020943531798HLA-B44:07AELALRSQL0.99780.98521221
MAML2-YAP1chr1196074547chr111020943531798HLA-B44:26AELALRSQL0.99780.98521221
MAML2-YAP1chr1196074547chr111020943531798HLA-B44:13AELALRSQL0.99780.98521221
MAML2-YAP1chr1196074547chr111020943531798HLA-C03:06SALIAELAL0.970.992817
MAML2-YAP1chr1196074547chr111020943531798HLA-B35:13SALIAELAL0.95580.8239817
MAML2-YAP1chr1196074547chr111020943531798HLA-A74:01ALIAELALR0.93650.6727918
MAML2-YAP1chr1196074547chr111020943531798HLA-C08:01SALIAELAL0.91770.99817
MAML2-YAP1chr1196074547chr111020943531798HLA-C16:01SALIAELAL0.90940.9793817
MAML2-YAP1chr1196074547chr111020943531798HLA-B35:22SALIAELAL0.90770.5195817
MAML2-YAP1chr1196074547chr111020943531798HLA-B18:11AELALRSQL0.84250.86711221
MAML2-YAP1chr1196074547chr111020943531798HLA-B35:09SALIAELAL0.84050.9578817
MAML2-YAP1chr1196074547chr111020943531798HLA-B41:03AELALRSQL0.78760.76591221
MAML2-YAP1chr1196074547chr111020943531798HLA-C17:01SALIAELAL0.74020.9592817
MAML2-YAP1chr1196074547chr111020943531798HLA-B39:02AELALRSQL0.63460.98271221
MAML2-YAP1chr1196074547chr111020943531798HLA-B48:02AELALRSQL0.47490.94031221
MAML2-YAP1chr1196074547chr111020943531798HLA-B50:05AELALRSQL0.39990.80941221
MAML2-YAP1chr1196074547chr111020943531798HLA-B50:04AELALRSQL0.39990.80941221
MAML2-YAP1chr1196074547chr111020943531798HLA-B07:13SALIAELAL0.32720.8384817
MAML2-YAP1chr1196074547chr111020943531798HLA-B15:53AELALRSQL0.17410.82911221
MAML2-YAP1chr1196074547chr111020943531798HLA-B27:08QRNSALIAEL0.99990.67515
MAML2-YAP1chr1196074547chr111020943531798HLA-B27:06QRNSALIAEL0.99980.7341515
MAML2-YAP1chr1196074547chr111020943531798HLA-B27:09QRNSALIAEL0.99980.7587515

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Potential FusionNeoAntigen Information of MAML2-YAP1 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 MAML2-YAP1

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
8064RNSALIAELALRSQMAML2YAP1chr1196074547chr111020943531798

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MAML2-YAP1

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-B14:023BVN8064RNSALIAELALRSQ-7.9962-8.1096
HLA-B14:023BVN8064RNSALIAELALRSQ-5.70842-6.74372
HLA-B52:013W398064RNSALIAELALRSQ-6.83737-6.95077
HLA-B52:013W398064RNSALIAELALRSQ-4.4836-5.5189
HLA-A11:014UQ28064RNSALIAELALRSQ-10.0067-10.1201
HLA-A11:014UQ28064RNSALIAELALRSQ-9.03915-10.0745
HLA-A24:025HGA8064RNSALIAELALRSQ-6.56204-6.67544
HLA-A24:025HGA8064RNSALIAELALRSQ-5.42271-6.45801
HLA-B44:053DX88064RNSALIAELALRSQ-7.85648-8.89178
HLA-B44:053DX88064RNSALIAELALRSQ-5.3978-5.5112
HLA-A02:016TDR8064RNSALIAELALRSQ-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of MAML2-YAP1

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
MAML2-YAP1chr1196074547chr111020943531221AELALRSQLGCGGAGTTAGCCCTGCGTAGCCAGTTA
MAML2-YAP1chr1196074547chr111020943531222AELALRSQLPGCGGAGTTAGCCCTGCGTAGCCAGTTACCA
MAML2-YAP1chr1196074547chr11102094353515QRNSALIAELCAGAGGAACTCAGCCCTGATTGCGGAGTTA
MAML2-YAP1chr1196074547chr11102094353516QRNSALIAELACAGAGGAACTCAGCCCTGATTGCGGAGTTAGCC
MAML2-YAP1chr1196074547chr11102094353817SALIAELALTCAGCCCTGATTGCGGAGTTAGCCCTG
MAML2-YAP1chr1196074547chr11102094353918ALIAELALRGCCCTGATTGCGGAGTTAGCCCTGCGT

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 MAML2-YAP1

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
SKCMMAML2-YAP1chr1196074547ENST00000524717chr11102094353ENST00000282441TCGA-EE-A17Z-06A

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Potential target of CAR-T therapy development for MAML2-YAP1

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 MAML2-YAP1

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 MAML2-YAP1

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
HgeneMAML2C0087031Juvenile-Onset Still Disease1CTD_human
HgeneMAML2C3495559Juvenile arthritis1CTD_human
HgeneMAML2C3714758Juvenile psoriatic arthritis1CTD_human
HgeneMAML2C4552091Polyarthritis, Juvenile, Rheumatoid Factor Negative1CTD_human
HgeneMAML2C4704862Polyarthritis, Juvenile, Rheumatoid Factor Positive1CTD_human