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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:AVIL-HIP1R

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: AVIL-HIP1R
FusionPDB ID: 8535
FusionGDB2.0 ID: 8535
HgeneTgene
Gene symbol

AVIL

HIP1R

Gene ID

10677

9026

Gene nameadvillinhuntingtin interacting protein 1 related
SynonymsADVIL|DOC6|NPHS21|p92HIP12|HIP3|ILWEQ
Cytomap

12q14.1

12q24.31

Type of geneprotein-codingprotein-coding
Descriptionadvillinhuntingtin-interacting protein 1-related proteinHIP-12HIP1-related proteinhuntingtin interacting protein 12
Modification date2020031320200320
UniProtAcc

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}.

O75146

Main function of 5'-partner protein: FUNCTION: Component of clathrin-coated pits and vesicles, that may link the endocytic machinery to the actin cytoskeleton. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis. {ECO:0000269|PubMed:11889126, ECO:0000269|PubMed:14732715}.
Ensembl transtripts involved in fusion geneENST idsENST00000257861, ENST00000537081, 
ENST00000550083, 
ENST00000537322, 
ENST00000253083, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 5 X 4=806 X 7 X 4=168
# samples 58
** MAII scorelog2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/168*10)=-1.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: AVIL [Title/Abstract] AND HIP1R [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: AVIL [Title/Abstract] AND HIP1R [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)AVIL(58200143)-HIP1R(123332578), # samples:2
Anticipated loss of major functional domain due to fusion event.AVIL-HIP1R 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.
AVIL-HIP1R 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.
AVIL-HIP1R 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.
AVIL-HIP1R 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
TgeneHIP1R

GO:0006919

activation of cysteine-type endopeptidase activity involved in apoptotic process

19255499

TgeneHIP1R

GO:0032092

positive regulation of protein binding

19255499

TgeneHIP1R

GO:0050821

protein stabilization

14732715



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/chr12:58200143/chr12:123332578)
- 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 AVIL (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 HIP1R (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)
ENST00000537081AVILchr1258200143-ENST00000253083HIP1Rchr12123332578+59711650047631587
ENST00000257861AVILchr1258200143-ENST00000253083HIP1Rchr12123332578+6423210243152151594

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
ENST00000537081ENST00000253083AVILchr1258200143-HIP1Rchr12123332578+0.003807050.99619293
ENST00000257861ENST00000253083AVILchr1258200143-HIP1Rchr12123332578+0.0051115420.9948885

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 AVIL-HIP1R

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
AVILchr1258200143HIP1Rchr121233325781650550LRTQAEHYLWYGKAISISKAINTQEA
AVILchr1258200143HIP1Rchr121233325782102557LRTQAEHYLWYGKAISISKAINTQEA

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Potential FusionNeoAntigen Information of AVIL-HIP1R 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.
AVIL-HIP1R_58200143_123332578.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)
AVIL-HIP1Rchr1258200143chr121233325782102HLA-A30:08YGKAISISK0.98450.63941019
AVIL-HIP1Rchr1258200143chr121233325782102HLA-B39:06EHYLWYGKA0.9810.8249514
AVIL-HIP1Rchr1258200143chr121233325782102HLA-B52:01KAISISKAI0.57980.61851221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-A02:11YLWYGKAISI0.99530.5261717
AVIL-HIP1Rchr1258200143chr121233325782102HLA-A02:13YLWYGKAISI0.99420.5921717
AVIL-HIP1Rchr1258200143chr121233325782102HLA-A02:27YLWYGKAISI0.99410.5048717
AVIL-HIP1Rchr1258200143chr121233325782102HLA-A02:04YLWYGKAISI0.99150.6615717
AVIL-HIP1Rchr1258200143chr121233325782102HLA-A02:35YLWYGKAISI0.96710.5082717
AVIL-HIP1Rchr1258200143chr121233325782102HLA-A02:38YLWYGKAISI0.95750.5033717
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C03:07KAISISKAI0.9990.96321221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C15:06KAISISKAI0.99850.87281221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C03:19KAISISKAI0.99540.97081221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C03:08KAISISKAI0.9950.83561221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C06:03KAISISKAI0.98790.98361221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C12:04KAISISKAI0.98650.98341221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C12:12KAISISKAI0.9810.8681221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C02:06KAISISKAI0.92970.93921221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-B73:01EHYLWYGKA0.03050.7283514
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C15:02KAISISKAI0.99890.81691221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C15:05KAISISKAI0.99850.85631221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C03:17KAISISKAI0.9960.94081221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C03:05KAISISKAI0.9960.92541221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C03:04KAISISKAI0.99120.97391221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C03:03KAISISKAI0.99120.97391221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-A30:01YGKAISISK0.98450.75881019
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C16:02KAISISKAI0.98170.98241221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C12:03KAISISKAI0.97860.9491221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C16:04KAISISKAI0.96350.9351221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C03:06KAISISKAI0.95110.97341221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C16:01KAISISKAI0.85260.96011221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-B35:13KAISISKAI0.84690.84971221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-B07:13KAISISKAI0.64830.73391221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C04:04LWYGKAISI0.55060.9146817
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C17:01KAISISKAI0.48170.65191221
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C14:02HYLWYGKAI0.00780.9562615
AVIL-HIP1Rchr1258200143chr121233325782102HLA-C14:03HYLWYGKAI0.00780.9562615
AVIL-HIP1Rchr1258200143chr121233325782102HLA-A02:03YLWYGKAISI0.99410.5974717

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Potential FusionNeoAntigen Information of AVIL-HIP1R 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.
AVIL-HIP1R_58200143_123332578.msa

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)
AVIL-HIP1Rchr1258200143chr121233325782102DRB1-0102GKAISISKAINTQEA1126
AVIL-HIP1Rchr1258200143chr121233325782102DRB1-0123GKAISISKAINTQEA1126
AVIL-HIP1Rchr1258200143chr121233325782102DRB1-0704GKAISISKAINTQEA1126
AVIL-HIP1Rchr1258200143chr121233325782102DRB1-0906GKAISISKAINTQEA1126
AVIL-HIP1Rchr1258200143chr121233325782102DRB1-0906YGKAISISKAINTQE1025
AVIL-HIP1Rchr1258200143chr121233325782102DRB1-1367GKAISISKAINTQEA1126
AVIL-HIP1Rchr1258200143chr121233325782102DRB3-0201GKAISISKAINTQEA1126
AVIL-HIP1Rchr1258200143chr121233325782102DRB3-0201YGKAISISKAINTQE1025
AVIL-HIP1Rchr1258200143chr121233325782102DRB3-0204GKAISISKAINTQEA1126
AVIL-HIP1Rchr1258200143chr121233325782102DRB3-0204YGKAISISKAINTQE1025
AVIL-HIP1Rchr1258200143chr121233325782102DRB3-0224GKAISISKAINTQEA1126
AVIL-HIP1Rchr1258200143chr121233325782102DRB3-0224YGKAISISKAINTQE1025
AVIL-HIP1Rchr1258200143chr121233325782102DRB3-0301GKAISISKAINTQEA1126

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Fusion breakpoint peptide structures of AVIL-HIP1R

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
3558HYLWYGKAISISKAAVILHIP1Rchr1258200143chr121233325782102

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of AVIL-HIP1R

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-B14:023BVN3558HYLWYGKAISISKA-6.46878-6.66328
HLA-B14:023BVN3558HYLWYGKAISISKA-4.33704-5.09154
HLA-B52:013W393558HYLWYGKAISISKA-6.45088-7.20538
HLA-B52:013W393558HYLWYGKAISISKA-6.08714-6.28164
HLA-A11:014UQ23558HYLWYGKAISISKA-7.67344-8.42794
HLA-A24:025HGA3558HYLWYGKAISISKA-7.49907-7.69357
HLA-A24:025HGA3558HYLWYGKAISISKA-4.36357-5.11807
HLA-B27:056PYJ3558HYLWYGKAISISKA-8.53231-9.28681
HLA-B44:053DX83558HYLWYGKAISISKA-5.69992-5.89442
HLA-B44:053DX83558HYLWYGKAISISKA-3.58931-4.34381
HLA-A02:016TDR3558HYLWYGKAISISKA-7.78181-7.97631

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Vaccine Design for the FusionNeoAntigens of AVIL-HIP1R

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
AVIL-HIP1Rchr1258200143chr121233325781019YGKAISISKTATGGCAAGGCCATCAGCATCAGCAAA
AVIL-HIP1Rchr1258200143chr121233325781221KAISISKAIAAGGCCATCAGCATCAGCAAAGCCATC
AVIL-HIP1Rchr1258200143chr12123332578514EHYLWYGKAGAGCACTACCTGTGGTATGGCAAGGCC
AVIL-HIP1Rchr1258200143chr12123332578615HYLWYGKAICACTACCTGTGGTATGGCAAGGCCATC
AVIL-HIP1Rchr1258200143chr12123332578717YLWYGKAISITACCTGTGGTATGGCAAGGCCATCAGCATC
AVIL-HIP1Rchr1258200143chr12123332578817LWYGKAISICTGTGGTATGGCAAGGCCATCAGCATC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
AVIL-HIP1Rchr1258200143chr121233325781025YGKAISISKAINTQETATGGCAAGGCCATCAGCATCAGCAAAGCCATCAACACCCAGGAG
AVIL-HIP1Rchr1258200143chr121233325781126GKAISISKAINTQEAGGCAAGGCCATCAGCATCAGCAAAGCCATCAACACCCAGGAGGCC

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Information of the samples that have these potential fusion neoantigens of AVIL-HIP1R

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
GBMAVIL-HIP1Rchr1258200143ENST00000257861chr12123332578ENST00000253083TCGA-06-0129-01A

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Potential target of CAR-T therapy development for AVIL-HIP1R

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 AVIL-HIP1R

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 AVIL-HIP1R

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