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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:AHRR-AVIL

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: AHRR-AVIL
FusionPDB ID: 3138
FusionGDB2.0 ID: 3138
HgeneTgene
Gene symbol

AHRR

AVIL

Gene ID

57491

10677

Gene namearyl-hydrocarbon receptor repressoradvillin
SynonymsAHH|AHHR|bHLHe77ADVIL|DOC6|NPHS21|p92
Cytomap

5p15.33

12q14.1

Type of geneprotein-codingprotein-coding
Descriptionaryl hydrocarbon receptor repressorahR repressoraryl hydrocarbon hydroxylase regulatorclass E basic helix-loop-helix protein 77dioxin receptor repressoradvillin
Modification date2020032220200313
UniProtAcc

A9YTQ3

Main function of 5'-partner protein: FUNCTION: Mediates dioxin toxicity and is involved in regulation of cell growth and differentiation. Represses the transcription activity of AHR by competing with this transcription factor for heterodimer formation with the ARNT and subsequently binding to the xenobiotic response element (XRE) sequence present in the promoter regulatory region of variety of genes. Represses CYP1A1 by binding the XRE sequence and recruiting ANKRA2, HDAC4 and/or HDAC5. Autoregulates its expression by associating with its own XRE site. {ECO:0000269|PubMed:17890447, ECO:0000269|PubMed:18172554}.

O75366

Main function of 5'-partner protein: FUNCTION: Ca(2+)-regulated actin-binding protein which plays an important role in actin bundling (PubMed:29058690). May have a unique function in the morphogenesis of neuronal cells which form ganglia. Required for SREC1-mediated regulation of neurite-like outgrowth. Plays a role in regenerative sensory axon outgrowth and remodeling processes after peripheral injury in neonates. Involved in the formation of long fine actin-containing filopodia-like structures in fibroblast. Plays a role in ciliogenesis. In podocytes, controls lamellipodia formation through the regulation of EGF-induced diacylglycerol generation by PLCE1 and ARP2/3 complex assembly (PubMed:29058690). {ECO:0000269|PubMed:20393563, ECO:0000269|PubMed:29058690}.
Ensembl transtripts involved in fusion geneENST idsENST00000316418, ENST00000505113, 
ENST00000506456, ENST00000512529, 
ENST00000515206, 
ENST00000550083, 
ENST00000257861, ENST00000537081, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 4=14420 X 12 X 9=2160
# samples 720
** MAII scorelog2(7/144*10)=-1.04064198449735
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(20/2160*10)=-3.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: AHRR [Title/Abstract] AND AVIL [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: AHRR [Title/Abstract] AND AVIL [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)AHRR(376831)-AVIL(58193703), # samples:3
Anticipated loss of major functional domain due to fusion event.AHRR-AVIL 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.
AHRR-AVIL 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.
AHRR-AVIL 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.
AHRR-AVIL 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


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/chr5:376831/chr12:58193703)
- 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 AHRR (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 AVIL (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)
ENST00000505113AHRRchr5376831+ENST00000537081AVILchr1258193703-114740744646200
ENST00000505113AHRRchr5376831+ENST00000257861AVILchr1258193703-64740744646201
ENST00000316418AHRRchr5376831+ENST00000537081AVILchr1258193703-114740744646200
ENST00000316418AHRRchr5376831+ENST00000257861AVILchr1258193703-64740744646201

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
ENST00000505113ENST00000537081AHRRchr5376831+AVILchr1258193703-0.0071976710.9928023
ENST00000505113ENST00000257861AHRRchr5376831+AVILchr1258193703-0.0116397890.98836017
ENST00000316418ENST00000537081AHRRchr5376831+AVILchr1258193703-0.0071976710.9928023
ENST00000316418ENST00000257861AHRRchr5376831+AVILchr1258193703-0.0116397890.98836017

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 AHRR-AVIL

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
AHRRchr5376831AVILchr1258193703407121AGSAVLEGRLLLEDMKNATLSLNSND

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Potential FusionNeoAntigen Information of AHRR-AVIL 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.
AHRR-AVIL_376831_58193703.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)
AHRR-AVILchr5376831chr1258193703407HLA-A02:27LLLEDMKNA0.94880.7546918
AHRR-AVILchr5376831chr1258193703407HLA-A02:22LLLEDMKNA0.94820.8036918
AHRR-AVILchr5376831chr1258193703407HLA-A02:67LLLEDMKNA0.9470.6916918
AHRR-AVILchr5376831chr1258193703407HLA-A02:24LLLEDMKNA0.9470.6916918
AHRR-AVILchr5376831chr1258193703407HLA-A02:30LLLEDMKNA0.9470.6916918
AHRR-AVILchr5376831chr1258193703407HLA-A02:60LLLEDMKNA0.94640.6852918
AHRR-AVILchr5376831chr1258193703407HLA-A02:21LLLEDMKNA0.93110.7789918
AHRR-AVILchr5376831chr1258193703407HLA-A02:13LLLEDMKNA0.92230.7761918
AHRR-AVILchr5376831chr1258193703407HLA-A02:16LLLEDMKNA0.91440.6368918
AHRR-AVILchr5376831chr1258193703407HLA-A02:19LLLEDMKNA0.8330.6415918
AHRR-AVILchr5376831chr1258193703407HLA-A02:38LLLEDMKNA0.82420.7197918
AHRR-AVILchr5376831chr1258193703407HLA-A02:20LLLEDMKNA0.72520.7028918
AHRR-AVILchr5376831chr1258193703407HLA-A02:29LLLEDMKNA0.72480.6952918
AHRR-AVILchr5376831chr1258193703407HLA-B39:13LEDMKNATL0.57660.93791120
AHRR-AVILchr5376831chr1258193703407HLA-B41:01LEDMKNATL0.36870.93091120
AHRR-AVILchr5376831chr1258193703407HLA-A02:67LLLEDMKNATL0.99190.6217920
AHRR-AVILchr5376831chr1258193703407HLA-A02:24LLLEDMKNATL0.99190.6217920
AHRR-AVILchr5376831chr1258193703407HLA-A02:30LLLEDMKNATL0.99190.6217920
AHRR-AVILchr5376831chr1258193703407HLA-A02:60LLLEDMKNATL0.99160.5926920
AHRR-AVILchr5376831chr1258193703407HLA-A02:04LLLEDMKNATL0.990.703920
AHRR-AVILchr5376831chr1258193703407HLA-A02:16LLLEDMKNATL0.9820.5468920
AHRR-AVILchr5376831chr1258193703407HLA-A02:29LLLEDMKNATL0.91160.6222920
AHRR-AVILchr5376831chr1258193703407HLA-C04:10LEDMKNATL0.99960.76991120
AHRR-AVILchr5376831chr1258193703407HLA-C08:15LEDMKNATL0.99940.95771120
AHRR-AVILchr5376831chr1258193703407HLA-B27:14GRLLLEDMK0.99020.8671716
AHRR-AVILchr5376831chr1258193703407HLA-A02:01LLLEDMKNA0.9470.6916918
AHRR-AVILchr5376831chr1258193703407HLA-B14:03LEDMKNATL0.7550.82811120
AHRR-AVILchr5376831chr1258193703407HLA-B39:09LEDMKNATL0.70320.58651120
AHRR-AVILchr5376831chr1258193703407HLA-B39:08LEDMKNATL0.67210.90071120
AHRR-AVILchr5376831chr1258193703407HLA-B39:12LEDMKNATL0.56530.93651120
AHRR-AVILchr5376831chr1258193703407HLA-B39:05LEDMKNATL0.52210.91781120
AHRR-AVILchr5376831chr1258193703407HLA-B39:08LLEDMKNATL0.68880.9141020
AHRR-AVILchr5376831chr1258193703407HLA-A02:01LLLEDMKNATL0.99190.6217920
AHRR-AVILchr5376831chr1258193703407HLA-B39:08LEDMKNATLSL0.99040.92971122
AHRR-AVILchr5376831chr1258193703407HLA-C18:01LEDMKNATL0.99940.80381120
AHRR-AVILchr5376831chr1258193703407HLA-C08:02LEDMKNATL0.99940.95771120
AHRR-AVILchr5376831chr1258193703407HLA-B40:04LEDMKNATL0.99870.67051120
AHRR-AVILchr5376831chr1258193703407HLA-A02:03LLLEDMKNA0.96960.822918
AHRR-AVILchr5376831chr1258193703407HLA-A02:06LLLEDMKNA0.93110.7789918
AHRR-AVILchr5376831chr1258193703407HLA-B39:02LEDMKNATL0.65370.9381120
AHRR-AVILchr5376831chr1258193703407HLA-B39:31LEDMKNATL0.62370.93041120
AHRR-AVILchr5376831chr1258193703407HLA-B39:11LEDMKNATL0.62330.88061120
AHRR-AVILchr5376831chr1258193703407HLA-B41:03LEDMKNATL0.45780.64551120

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Potential FusionNeoAntigen Information of AHRR-AVIL 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 AHRR-AVIL

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
1750EGRLLLEDMKNATLAHRRAVILchr5376831chr1258193703407

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of AHRR-AVIL

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-B14:023BVN1750EGRLLLEDMKNATL-7.9962-8.1096
HLA-B14:023BVN1750EGRLLLEDMKNATL-5.70842-6.74372
HLA-B52:013W391750EGRLLLEDMKNATL-6.83737-6.95077
HLA-B52:013W391750EGRLLLEDMKNATL-4.4836-5.5189
HLA-A11:014UQ21750EGRLLLEDMKNATL-10.0067-10.1201
HLA-A11:014UQ21750EGRLLLEDMKNATL-9.03915-10.0745
HLA-A24:025HGA1750EGRLLLEDMKNATL-6.56204-6.67544
HLA-A24:025HGA1750EGRLLLEDMKNATL-5.42271-6.45801
HLA-B44:053DX81750EGRLLLEDMKNATL-7.85648-8.89178
HLA-B44:053DX81750EGRLLLEDMKNATL-5.3978-5.5112
HLA-A02:016TDR1750EGRLLLEDMKNATL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of AHRR-AVIL

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
AHRR-AVILchr5376831chr12581937031020LLEDMKNATLCTGTTGGAGGACATGAAGAATGCAACCCTC
AHRR-AVILchr5376831chr12581937031120LEDMKNATLTTGGAGGACATGAAGAATGCAACCCTC
AHRR-AVILchr5376831chr12581937031122LEDMKNATLSLTTGGAGGACATGAAGAATGCAACCCTCTCCCTG
AHRR-AVILchr5376831chr1258193703716GRLLLEDMKGGAAGGCTGCTGTTGGAGGACATGAAG
AHRR-AVILchr5376831chr1258193703918LLLEDMKNACTGCTGTTGGAGGACATGAAGAATGCA
AHRR-AVILchr5376831chr1258193703920LLLEDMKNATLCTGCTGTTGGAGGACATGAAGAATGCAACCCTC

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 AHRR-AVIL

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
SARCAHRR-AVILchr5376831ENST00000316418chr1258193703ENST00000257861TCGA-DX-A2IZ-01A

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Potential target of CAR-T therapy development for AHRR-AVIL

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 AHRR-AVIL

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 AHRR-AVIL

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