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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:ARHGAP42-YAP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ARHGAP42-YAP1
FusionPDB ID: 6118
FusionGDB2.0 ID: 6118
HgeneTgene
Gene symbol

ARHGAP42

YAP1

Gene ID

143872

10413

Gene nameRho GTPase activating protein 42Yes1 associated transcriptional regulator
SynonymsAD031|GRAF3|TMEM133COB1|YAP|YAP2|YAP65|YKI
Cytomap

11q22.1

11q22.1

Type of geneprotein-codingprotein-coding
Descriptionrho GTPase-activating protein 42rho-type GTPase-activating protein 42transmembrane protein 133transcriptional 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

A6NI28

Main function of 5'-partner protein: FUNCTION: May influence blood pressure by functioning as a GTPase-activating protein for RHOA in vascular smooth muscle. {ECO:0000269|PubMed:24335996}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000298815, ENST00000524892, 
ENST00000534060, 
ENST00000528834, 
ENST00000282441, ENST00000345877, 
ENST00000524575, ENST00000526343, 
ENST00000531439, ENST00000537274, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 7 X 7=53920 X 10 X 13=2600
# samples 1221
** MAII scorelog2(12/539*10)=-2.16725086714399
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: ARHGAP42 [Title/Abstract] AND YAP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ARHGAP42 [Title/Abstract] AND YAP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ARHGAP42(100558563)-YAP1(102076624), # samples:1
Anticipated loss of major functional domain due to fusion event.ARHGAP42-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.
ARHGAP42-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.
ARHGAP42-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.
ARHGAP42-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.
* 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
HgeneARHGAP42

GO:0090630

activation of GTPase activity

24335996

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/chr11:100558563/chr11:102076624)
- 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 ARHGAP42 (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)
ENST00000524892ARHGAP42chr11100558563+ENST00000526343YAP1chr11102076624+149718026844272
ENST00000524892ARHGAP42chr11100558563+ENST00000282441YAP1chr11102076624+437618026892288
ENST00000524892ARHGAP42chr11100558563+ENST00000537274YAP1chr11102076624+434018026856276
ENST00000524892ARHGAP42chr11100558563+ENST00000345877YAP1chr11102076624+434018026856276
ENST00000524892ARHGAP42chr11100558563+ENST00000531439YAP1chr11102076624+86818026844272
ENST00000524892ARHGAP42chr11100558563+ENST00000524575YAP1chr11102076624+110518026892288
ENST00000298815ARHGAP42chr11100558563+ENST00000526343YAP1chr11102076624+14741573821272
ENST00000298815ARHGAP42chr11100558563+ENST00000282441YAP1chr11102076624+43531573869288
ENST00000298815ARHGAP42chr11100558563+ENST00000537274YAP1chr11102076624+43171573833276
ENST00000298815ARHGAP42chr11100558563+ENST00000345877YAP1chr11102076624+43171573833276
ENST00000298815ARHGAP42chr11100558563+ENST00000531439YAP1chr11102076624+8451573821272
ENST00000298815ARHGAP42chr11100558563+ENST00000524575YAP1chr11102076624+10821573869288

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
ENST00000524892ENST00000526343ARHGAP42chr11100558563+YAP1chr11102076624+0.0073570870.99264294
ENST00000524892ENST00000282441ARHGAP42chr11100558563+YAP1chr11102076624+0.0005749240.99942505
ENST00000524892ENST00000537274ARHGAP42chr11100558563+YAP1chr11102076624+0.0004728090.9995272
ENST00000524892ENST00000345877ARHGAP42chr11100558563+YAP1chr11102076624+0.0004728090.9995272
ENST00000524892ENST00000531439ARHGAP42chr11100558563+YAP1chr11102076624+0.0122359960.98776406
ENST00000524892ENST00000524575ARHGAP42chr11100558563+YAP1chr11102076624+0.0090612230.9909388
ENST00000298815ENST00000526343ARHGAP42chr11100558563+YAP1chr11102076624+0.0068550810.99314487
ENST00000298815ENST00000282441ARHGAP42chr11100558563+YAP1chr11102076624+0.0005730910.99942696
ENST00000298815ENST00000537274ARHGAP42chr11100558563+YAP1chr11102076624+0.0004706580.99952936
ENST00000298815ENST00000345877ARHGAP42chr11100558563+YAP1chr11102076624+0.0004706580.99952936
ENST00000298815ENST00000531439ARHGAP42chr11100558563+YAP1chr11102076624+0.0111280310.988872
ENST00000298815ENST00000524575ARHGAP42chr11100558563+YAP1chr11102076624+0.0086090580.99139094

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 ARHGAP42-YAP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ARHGAP42chr11100558563YAP1chr1110207662415752IKDGSLLIGALRTMNQRISQSAPVKQ
ARHGAP42chr11100558563YAP1chr1110207662418052IKDGSLLIGALRTMNQRISQSAPVKQ

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Potential FusionNeoAntigen Information of ARHGAP42-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.
ARHGAP42-YAP1_100558563_102076624.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)
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-B15:25LLIGALRTM0.97470.9798514
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-B15:02LLIGALRTM0.97230.9806514
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-B46:01LLIGALRTM0.95940.6041514
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-A02:04LLIGALRTM0.93060.953514
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-A02:17LLIGALRTM0.92060.8665514
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-A31:06GALRTMNQR0.90770.7034817
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-A30:08RTMNQRISQ0.9010.80481120
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-A30:08RTMNQRISQSA0.99130.79831122
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-B15:07LLIGALRTM0.9970.7089514
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-B15:04LLIGALRTM0.97710.9568514
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-A31:01GALRTMNQR0.96120.8233817
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-B15:39LLIGALRTM0.97470.9566514
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-C03:02LLIGALRTM0.97030.9863514
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-B15:73LLIGALRTM0.91670.9193514
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-A30:01RTMNQRISQ0.90990.91251120
ARHGAP42-YAP1chr11100558563chr11102076624157HLA-B15:30LLIGALRTM0.84870.9436514

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Potential FusionNeoAntigen Information of ARHGAP42-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 ARHGAP42-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
5096LIGALRTMNQRISQARHGAP42YAP1chr11100558563chr11102076624157

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ARHGAP42-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-B14:023BVN5096LIGALRTMNQRISQ-7.9962-8.1096
HLA-B14:023BVN5096LIGALRTMNQRISQ-5.70842-6.74372
HLA-B52:013W395096LIGALRTMNQRISQ-6.83737-6.95077
HLA-B52:013W395096LIGALRTMNQRISQ-4.4836-5.5189
HLA-A11:014UQ25096LIGALRTMNQRISQ-10.0067-10.1201
HLA-A11:014UQ25096LIGALRTMNQRISQ-9.03915-10.0745
HLA-A24:025HGA5096LIGALRTMNQRISQ-6.56204-6.67544
HLA-A24:025HGA5096LIGALRTMNQRISQ-5.42271-6.45801
HLA-B44:053DX85096LIGALRTMNQRISQ-7.85648-8.89178
HLA-B44:053DX85096LIGALRTMNQRISQ-5.3978-5.5112
HLA-A02:016TDR5096LIGALRTMNQRISQ-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ARHGAP42-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
ARHGAP42-YAP1chr11100558563chr111020766241120RTMNQRISQTGAGGACCATGAACCAGAGAATCAGTC
ARHGAP42-YAP1chr11100558563chr111020766241122RTMNQRISQSATGAGGACCATGAACCAGAGAATCAGTCAGAGTG
ARHGAP42-YAP1chr11100558563chr11102076624514LLIGALRTMCTCTGCTCATTGGGGCGTTGAGGACCA
ARHGAP42-YAP1chr11100558563chr11102076624817GALRTMNQRTTGGGGCGTTGAGGACCATGAACCAGA

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 ARHGAP42-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
HNSCARHGAP42-YAP1chr11100558563ENST00000298815chr11102076624ENST00000282441TCGA-CV-7235-01A

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Potential target of CAR-T therapy development for ARHGAP42-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 ARHGAP42-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 ARHGAP42-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