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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-KMO

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ARHGAP42-KMO
FusionPDB ID: 6112
FusionGDB2.0 ID: 6112
HgeneTgene
Gene symbol

ARHGAP42

KMO

Gene ID

143872

8564

Gene nameRho GTPase activating protein 42kynurenine 3-monooxygenase
SynonymsAD031|GRAF3|TMEM133dJ317G22.1
Cytomap

11q22.1

1q43

Type of geneprotein-codingprotein-coding
Descriptionrho GTPase-activating protein 42rho-type GTPase-activating protein 42transmembrane protein 133kynurenine 3-monooxygenasekynurenine 3-hydroxylase
Modification date2020031320200313
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}.

O15229

Main function of 5'-partner protein: FUNCTION: Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn) (PubMed:29429898, PubMed:23575632, PubMed:26752518, PubMed:28604669, PubMed:29208702). Required for synthesis of quinolinic acid, a neurotoxic NMDA receptor antagonist and potential endogenous inhibitor of NMDA receptor signaling in axonal targeting, synaptogenesis and apoptosis during brain development. Quinolinic acid may also affect NMDA receptor signaling in pancreatic beta cells, osteoblasts, myocardial cells, and the gastrointestinal tract (Probable). {ECO:0000269|PubMed:23575632, ECO:0000269|PubMed:26752518, ECO:0000269|PubMed:28604669, ECO:0000269|PubMed:29208702, ECO:0000269|PubMed:29429898, ECO:0000305|PubMed:12402501}.
Ensembl transtripts involved in fusion geneENST idsENST00000534060, ENST00000298815, 
ENST00000524892, 
ENST00000366558, 
ENST00000366559, ENST00000366557, 
ENST00000484628, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 7 X 7=5393 X 3 X 3=27
# samples 124
** MAII scorelog2(12/539*10)=-2.16725086714399
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/27*10)=0.567040592723894
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: ARHGAP42 [Title/Abstract] AND KMO [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ARHGAP42(100730356)-KMO(241749981), # samples:3
Anticipated loss of major functional domain due to fusion event.ARHGAP42-KMO 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-KMO 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

TgeneKMO

GO:0009651

response to salt stress

10672018

TgeneKMO

GO:0019674

NAD metabolic process

23575632|29429898

TgeneKMO

GO:0070189

kynurenine metabolic process

10672018|26752518|29208702|29429898



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/chr11:100730356/chr1:241749981)
- 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 KMO (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)
ENST00000524892ARHGAP42chr11100730356+ENST00000366558KMOchr1241749981+101041026874282
ENST00000524892ARHGAP42chr11100730356+ENST00000366559KMOchr1241749981+440341026913295
ENST00000298815ARHGAP42chr11100730356+ENST00000366558KMOchr1241749981+9873873851282
ENST00000298815ARHGAP42chr11100730356+ENST00000366559KMOchr1241749981+43803873890295
ENST00000524892ARHGAP42chr11100730356+ENST00000366558KMOchr1241749980+101041026874282
ENST00000524892ARHGAP42chr11100730356+ENST00000366559KMOchr1241749980+440341026913295
ENST00000298815ARHGAP42chr11100730356+ENST00000366558KMOchr1241749980+9873873851282
ENST00000298815ARHGAP42chr11100730356+ENST00000366559KMOchr1241749980+43803873890295

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
ENST00000524892ENST00000366558ARHGAP42chr11100730356+KMOchr1241749981+0.0033334420.9966666
ENST00000524892ENST00000366559ARHGAP42chr11100730356+KMOchr1241749981+0.0017661060.9982339
ENST00000298815ENST00000366558ARHGAP42chr11100730356+KMOchr1241749981+0.0031186590.99688137
ENST00000298815ENST00000366559ARHGAP42chr11100730356+KMOchr1241749981+0.0017608490.99823916
ENST00000524892ENST00000366558ARHGAP42chr11100730356+KMOchr1241749980+0.0033334420.9966666
ENST00000524892ENST00000366559ARHGAP42chr11100730356+KMOchr1241749980+0.0017661060.9982339
ENST00000298815ENST00000366558ARHGAP42chr11100730356+KMOchr1241749980+0.0031186590.99688137
ENST00000298815ENST00000366559ARHGAP42chr11100730356+KMOchr1241749980+0.0017608490.99823916

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-KMO

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ARHGAP42chr11100730356KMOchr1241749980387128LEKFRKEQIGAAKGFEDCLVFDELMD
ARHGAP42chr11100730356KMOchr1241749980410128LEKFRKEQIGAAKGFEDCLVFDELMD
ARHGAP42chr11100730356KMOchr1241749981387128LEKFRKEQIGAAKGFEDCLVFDELMD
ARHGAP42chr11100730356KMOchr1241749981410128LEKFRKEQIGAAKGFEDCLVFDELMD

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Potential FusionNeoAntigen Information of ARHGAP42-KMO 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-KMO_100730356_241749980.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-KMOchr11100730356chr1241749980387HLA-B44:05EQIGAAKGF0.57020.726615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:18EQIGAAKGF0.49030.8552615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:01KEQIGAAKGF0.99110.9239515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:03KEQIGAAKGF0.99080.9644515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:02KEQIGAAKGF0.98960.5065515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:05KEQIGAAKGF0.98250.6613515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B47:01KEQIGAAKGF0.9820.5424515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:03AKGFEDCLVF0.9760.9141121
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:21EQIGAAKGF0.85670.9489615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:31EQIGAAKGF0.79770.9072615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:08EQIGAAKGF0.73390.6689615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:09KEQIGAAKGF0.99280.7195515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:08KEQIGAAKGF0.99210.6385515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:07KEQIGAAKGF0.98690.7821515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:10KEQIGAAKGF0.94260.7351515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B18:04EQIGAAKGF0.88470.8016615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:12EQIGAAKGF0.78630.9581615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-A25:01EQIGAAKGF0.78520.9013615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B35:20EQIGAAKGF0.77190.9414615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:53EQIGAAKGF0.74430.9342615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:13EQIGAAKGF0.70980.9288615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:54EQIGAAKGF0.6070.9161615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B48:02EQIGAAKGF0.58380.9316615
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:53KEQIGAAKGF0.99330.9156515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:50KEQIGAAKGF0.99120.9259515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:33KEQIGAAKGF0.99110.9239515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:125KEQIGAAKGF0.99110.9239515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:34KEQIGAAKGF0.99110.9239515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:07KEQIGAAKGF0.99080.9644515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:26KEQIGAAKGF0.99080.9644515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:13KEQIGAAKGF0.99080.9644515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:135KEQIGAAKGF0.99030.922515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B44:22KEQIGAAKGF0.98960.5065515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:54KEQIGAAKGF0.98910.8918515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:68KEQIGAAKGF0.98660.68515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:24KEQIGAAKGF0.98590.9595515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:35KEQIGAAKGF0.98530.9261515
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:54AKGFEDCLVF0.96270.94111121
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:54RKEQIGAAKGF0.9990.8374415
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:68RKEQIGAAKGF0.9990.7099415
ARHGAP42-KMOchr11100730356chr1241749980387HLA-B15:24RKEQIGAAKGF0.99790.9337415

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Potential FusionNeoAntigen Information of ARHGAP42-KMO 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-KMO

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
2050EQIGAAKGFEDCLVARHGAP42KMOchr11100730356chr1241749980387

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ARHGAP42-KMO

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-B14:023BVN2050EQIGAAKGFEDCLV-7.15543-7.26883
HLA-B14:023BVN2050EQIGAAKGFEDCLV-4.77435-5.80965
HLA-B52:013W392050EQIGAAKGFEDCLV-6.80875-6.92215
HLA-B52:013W392050EQIGAAKGFEDCLV-4.20386-5.23916
HLA-A11:014UQ22050EQIGAAKGFEDCLV-7.5194-8.5547
HLA-A11:014UQ22050EQIGAAKGFEDCLV-6.9601-7.0735
HLA-A24:025HGA2050EQIGAAKGFEDCLV-7.52403-7.63743
HLA-A24:025HGA2050EQIGAAKGFEDCLV-5.82433-6.85963
HLA-B27:056PYJ2050EQIGAAKGFEDCLV-3.28285-4.31815
HLA-B44:053DX82050EQIGAAKGFEDCLV-5.91172-6.94702
HLA-B44:053DX82050EQIGAAKGFEDCLV-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ARHGAP42-KMO

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-KMOchr11100730356chr12417499801121AKGFEDCLVFGCAAAAGGCTTTGAAGACTGCTTGGTATTT
ARHGAP42-KMOchr11100730356chr1241749980415RKEQIGAAKGFCGAAAAGAACAGATAGGTGCAGCAAAAGGCTTT
ARHGAP42-KMOchr11100730356chr1241749980515KEQIGAAKGFAAAGAACAGATAGGTGCAGCAAAAGGCTTT
ARHGAP42-KMOchr11100730356chr1241749980615EQIGAAKGFGAACAGATAGGTGCAGCAAAAGGCTTT

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-KMO

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
LIHCARHGAP42-KMOchr11100730356ENST00000298815chr1241749980ENST00000366558TCGA-BC-A8YO

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

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
TgeneKMOchr11:100730356chr1:241749980ENST00000366557914385_4040453.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749980ENST00000366557914425_4450453.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749980ENST00000366558915385_4040474.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749980ENST00000366558915425_4450474.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749980ENST00000366559915385_4040487.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749980ENST00000366559915425_4450487.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749981ENST00000366557914385_4040453.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749981ENST00000366557914425_4450453.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749981ENST00000366558915385_4040474.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749981ENST00000366558915425_4450474.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749981ENST00000366559915385_4040487.0TransmembraneHelical
TgeneKMOchr11:100730356chr1:241749981ENST00000366559915425_4450487.0TransmembraneHelical

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-KMO

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-KMO

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