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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:GLI3-HIBADH

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GLI3-HIBADH
FusionPDB ID: 33276
FusionGDB2.0 ID: 33276
HgeneTgene
Gene symbol

GLI3

HIBADH

Gene ID

2737

11112

Gene nameGLI family zinc finger 33-hydroxyisobutyrate dehydrogenase
SynonymsACLS|GCPS|GLI3-190|GLI3FL|PAP-A|PAPA|PAPA1|PAPB|PHS|PPDIVNS5ATP1
Cytomap

7p14.1

7p15.2

Type of geneprotein-codingprotein-coding
Descriptiontranscriptional activator GLI3GLI-Kruppel family member GLI3glioma-associated oncogene family zinc finger 3oncogene GLI3zinc finger protein GLI33-hydroxyisobutyrate dehydrogenase, mitochondrial3'-hydroxyisobutyrate dehydrogenaseepididymis secretory sperm binding protein
Modification date2020031320200313
UniProtAcc

P10071

Main function of 5'-partner protein: FUNCTION: Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development. The full-length GLI3 form (GLI3FL) after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor. A proper balance between the GLI3 activator and the repressor GLI3R, rather than the repressor gradient itself or the activator/repressor ratio gradient, specifies limb digit number and identity. In concert with TRPS1, plays a role in regulating the size of the zone of distal chondrocytes, in restricting the zone of PTHLH expression in distal cells and in activating chondrocyte proliferation. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'. {ECO:0000269|PubMed:10693759, ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:17764085}.

P31937

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000479210, ENST00000395925, 
ENST00000437480, 
ENST00000265395, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 11 X 8=9689 X 8 X 7=504
# samples 1411
** MAII scorelog2(14/968*10)=-2.78958022032963
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/504*10)=-2.19592020997526
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GLI3 [Title/Abstract] AND HIBADH [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GLI3 [Title/Abstract] AND HIBADH [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GLI3(42187825)-HIBADH(27672064), # samples:3
Anticipated loss of major functional domain due to fusion event.GLI3-HIBADH 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.
GLI3-HIBADH 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
HgeneGLI3

GO:0000122

negative regulation of transcription by RNA polymerase II

10693759|12435627|19084012

HgeneGLI3

GO:0045892

negative regulation of transcription, DNA-templated

12435627|16254602|19084012

HgeneGLI3

GO:0045944

positive regulation of transcription by RNA polymerase II

17000779

HgeneGLI3

GO:0090090

negative regulation of canonical Wnt signaling pathway

17331723

TgeneHIBADH

GO:0006574

valine catabolic process

16466957



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/chr7:42187825/chr7:27672064)
- 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 GLI3 (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 HIBADH (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)
ENST00000395925GLI3chr742187825-ENST00000265395HIBADHchr727672064-19834523561210284
ENST00000395925GLI3chr742187825-ENST00000265395HIBADHchr727672045-196445285687200

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
ENST00000395925ENST00000265395GLI3chr742187825-HIBADHchr727672064-0.0012993020.9987006
ENST00000395925ENST00000265395GLI3chr742187825-HIBADHchr727672045-0.0093341230.99066585

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 GLI3-HIBADH

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GLI3chr742187825HIBADHchr72767206445232PWTPGMVTWSPTTVVSSPADVAEKAD

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Potential FusionNeoAntigen Information of GLI3-HIBADH 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.
GLI3-HIBADH_42187825_27672064.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)
GLI3-HIBADHchr742187825chr727672064452HLA-B52:01VTWSPTTV0.98980.9845614
GLI3-HIBADHchr742187825chr727672064452HLA-B15:16VTWSPTTVV0.92990.9038615
GLI3-HIBADHchr742187825chr727672064452HLA-B52:01VTWSPTTVV0.80890.9794615
GLI3-HIBADHchr742187825chr727672064452HLA-A02:35VTWSPTTVV0.76950.5324615
GLI3-HIBADHchr742187825chr727672064452HLA-A02:21VTWSPTTVV0.7380.632615
GLI3-HIBADHchr742187825chr727672064452HLA-A30:08VTWSPTTVV0.68370.7538615
GLI3-HIBADHchr742187825chr727672064452HLA-A02:20VTWSPTTVV0.67470.5189615
GLI3-HIBADHchr742187825chr727672064452HLA-C15:04VTWSPTTVV0.99910.8823615
GLI3-HIBADHchr742187825chr727672064452HLA-C15:06VTWSPTTVV0.99880.8806615
GLI3-HIBADHchr742187825chr727672064452HLA-C04:06VTWSPTTVV0.99770.966615
GLI3-HIBADHchr742187825chr727672064452HLA-C03:07VTWSPTTVV0.99750.9746615
GLI3-HIBADHchr742187825chr727672064452HLA-C12:04VTWSPTTVV0.98290.9912615
GLI3-HIBADHchr742187825chr727672064452HLA-C06:03VTWSPTTVV0.98270.99615
GLI3-HIBADHchr742187825chr727672064452HLA-C03:19VTWSPTTVV0.96790.9843615
GLI3-HIBADHchr742187825chr727672064452HLA-C03:08VTWSPTTVV0.96430.8907615
GLI3-HIBADHchr742187825chr727672064452HLA-C02:06VTWSPTTVV0.50540.9649615
GLI3-HIBADHchr742187825chr727672064452HLA-C15:02VTWSPTTVV0.99930.8917615
GLI3-HIBADHchr742187825chr727672064452HLA-C15:09VTWSPTTVV0.99910.8823615
GLI3-HIBADHchr742187825chr727672064452HLA-C15:05VTWSPTTVV0.99890.9346615
GLI3-HIBADHchr742187825chr727672064452HLA-C15:02MVTWSPTTV0.99860.9333514
GLI3-HIBADHchr742187825chr727672064452HLA-A68:02MVTWSPTTV0.99570.5682514
GLI3-HIBADHchr742187825chr727672064452HLA-A69:01MVTWSPTTV0.99040.6682514
GLI3-HIBADHchr742187825chr727672064452HLA-A69:01TVVSSPADV0.96280.60411221
GLI3-HIBADHchr742187825chr727672064452HLA-C12:03VTWSPTTVV0.96080.9715615
GLI3-HIBADHchr742187825chr727672064452HLA-C16:02VTWSPTTVV0.95510.9919615
GLI3-HIBADHchr742187825chr727672064452HLA-C03:06VTWSPTTVV0.95180.9879615
GLI3-HIBADHchr742187825chr727672064452HLA-A69:01VTWSPTTVV0.87680.6757615
GLI3-HIBADHchr742187825chr727672064452HLA-A02:14VTWSPTTVV0.74470.5705615
GLI3-HIBADHchr742187825chr727672064452HLA-A02:06VTWSPTTVV0.7380.632615
GLI3-HIBADHchr742187825chr727672064452HLA-C17:01VTWSPTTVV0.3830.9734615
GLI3-HIBADHchr742187825chr727672064452HLA-A68:02MVTWSPTTVV0.98270.5911515
GLI3-HIBADHchr742187825chr727672064452HLA-A69:01MVTWSPTTVV0.96510.6668515

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Potential FusionNeoAntigen Information of GLI3-HIBADH 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.
GLI3-HIBADH_42187825_27672064.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)
GLI3-HIBADHchr742187825chr727672064452DRB1-0422PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB1-0906PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB1-0906SPTTVVSSPADVAEK924
GLI3-HIBADHchr742187825chr727672064452DRB3-0201PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB3-0204PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB3-0224PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB4-0101PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB4-0101SPTTVVSSPADVAEK924
GLI3-HIBADHchr742187825chr727672064452DRB4-0101TTVVSSPADVAEKAD1126
GLI3-HIBADHchr742187825chr727672064452DRB4-0101WSPTTVVSSPADVAE823
GLI3-HIBADHchr742187825chr727672064452DRB4-0103PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB4-0103SPTTVVSSPADVAEK924
GLI3-HIBADHchr742187825chr727672064452DRB4-0103TTVVSSPADVAEKAD1126
GLI3-HIBADHchr742187825chr727672064452DRB4-0103WSPTTVVSSPADVAE823
GLI3-HIBADHchr742187825chr727672064452DRB4-0104PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB4-0104SPTTVVSSPADVAEK924
GLI3-HIBADHchr742187825chr727672064452DRB4-0104TTVVSSPADVAEKAD1126
GLI3-HIBADHchr742187825chr727672064452DRB4-0104WSPTTVVSSPADVAE823
GLI3-HIBADHchr742187825chr727672064452DRB4-0106PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB4-0106SPTTVVSSPADVAEK924
GLI3-HIBADHchr742187825chr727672064452DRB4-0106TTVVSSPADVAEKAD1126
GLI3-HIBADHchr742187825chr727672064452DRB4-0106WSPTTVVSSPADVAE823
GLI3-HIBADHchr742187825chr727672064452DRB4-0107PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB4-0107SPTTVVSSPADVAEK924
GLI3-HIBADHchr742187825chr727672064452DRB4-0107TTVVSSPADVAEKAD1126
GLI3-HIBADHchr742187825chr727672064452DRB4-0107WSPTTVVSSPADVAE823
GLI3-HIBADHchr742187825chr727672064452DRB4-0108PTTVVSSPADVAEKA1025
GLI3-HIBADHchr742187825chr727672064452DRB4-0108SPTTVVSSPADVAEK924
GLI3-HIBADHchr742187825chr727672064452DRB4-0108TTVVSSPADVAEKAD1126
GLI3-HIBADHchr742187825chr727672064452DRB4-0108WSPTTVVSSPADVAE823

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Fusion breakpoint peptide structures of GLI3-HIBADH

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
10335VTWSPTTVVSSPADGLI3HIBADHchr742187825chr727672064452

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GLI3-HIBADH

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-B14:023BVN10335VTWSPTTVVSSPAD-6.33173-6.44513
HLA-B14:023BVN10335VTWSPTTVVSSPAD-1.81046-2.84576
HLA-B52:013W3910335VTWSPTTVVSSPAD-5.92784-6.04124
HLA-B52:013W3910335VTWSPTTVVSSPAD-4.3074-5.3427
HLA-A24:025HGA10335VTWSPTTVVSSPAD-6.68795-7.72325
HLA-A24:025HGA10335VTWSPTTVVSSPAD-5.73606-5.84946
HLA-B44:053DX810335VTWSPTTVVSSPAD-6.99493-8.03023
HLA-B44:053DX810335VTWSPTTVVSSPAD-6.82556-6.93896
HLA-B35:011A1N10335VTWSPTTVVSSPAD-4.41016-5.44546
HLA-B35:011A1N10335VTWSPTTVVSSPAD-3.14066-3.25406
HLA-A02:016TDR10335VTWSPTTVVSSPAD-4.47214-5.50744

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Vaccine Design for the FusionNeoAntigens of GLI3-HIBADH

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
GLI3-HIBADHchr742187825chr7276720641221TVVSSPADVACCGTAGTATCTTCCCCAGCAGATGTT
GLI3-HIBADHchr742187825chr727672064514MVTWSPTTVATGGTTACATGGAGCCCCACTACCGTA
GLI3-HIBADHchr742187825chr727672064515MVTWSPTTVVATGGTTACATGGAGCCCCACTACCGTAGTA
GLI3-HIBADHchr742187825chr727672064614VTWSPTTVGTTACATGGAGCCCCACTACCGTA
GLI3-HIBADHchr742187825chr727672064615VTWSPTTVVGTTACATGGAGCCCCACTACCGTAGTA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
GLI3-HIBADHchr742187825chr7276720641025PTTVVSSPADVAEKACCCACTACCGTAGTATCTTCCCCAGCAGATGTTGCTGAAAAAGCT
GLI3-HIBADHchr742187825chr7276720641126TTVVSSPADVAEKADACTACCGTAGTATCTTCCCCAGCAGATGTTGCTGAAAAAGCTGAC
GLI3-HIBADHchr742187825chr727672064823WSPTTVVSSPADVAETGGAGCCCCACTACCGTAGTATCTTCCCCAGCAGATGTTGCTGAA
GLI3-HIBADHchr742187825chr727672064924SPTTVVSSPADVAEKAGCCCCACTACCGTAGTATCTTCCCCAGCAGATGTTGCTGAAAAA

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Information of the samples that have these potential fusion neoantigens of GLI3-HIBADH

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
LUADGLI3-HIBADHchr742187825ENST00000395925chr727672064ENST00000265395TCGA-50-6591-01A

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Potential target of CAR-T therapy development for GLI3-HIBADH

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 GLI3-HIBADH

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 GLI3-HIBADH

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