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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:GLI4-GALT

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GLI4-GALT
FusionPDB ID: 33283
FusionGDB2.0 ID: 33283
HgeneTgene
Gene symbol

GLI4

GALT

Gene ID

2738

2592

Gene nameGLI family zinc finger 4galactose-1-phosphate uridylyltransferase
SynonymsHKR4|ZNF928-
Cytomap

8q24.3

9p13.3

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein GLI4GLI-Kruppel family member GLI4 (oncogene HKR4)glioma-associated oncogene family zinc finger 4krueppel-related zinc finger protein 4galactose-1-phosphate uridylyltransferaseUDP-glucose--hexose-1-phosphate uridylyltransferasegal-1-P uridylyltransferasegalactose-1-phosphate uridyl transferase
Modification date2020031320200327
UniProtAcc

P10075

Main function of 5'-partner protein:

P07902

Main function of 5'-partner protein: FUNCTION: Plays an important role in galactose metabolism. {ECO:0000269|PubMed:22461411, ECO:0000269|PubMed:27005423}.
Ensembl transtripts involved in fusion geneENST idsENST00000340042, ENST00000344692, 
ENST00000517468, ENST00000521682, 
ENST00000523522, ENST00000523812, 
ENST00000488412, ENST00000378842, 
ENST00000556278, ENST00000450095, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=85 X 4 X 4=80
# samples 25
** MAII scorelog2(2/8*10)=1.32192809488736log2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GLI4 [Title/Abstract] AND GALT [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GLI4 [Title/Abstract] AND GALT [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GLI4(144351690)-GALT(34649406), # samples:1
Anticipated loss of major functional domain due to fusion event.GLI4-GALT 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.
GLI4-GALT 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.
GLI4-GALT 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.
GLI4-GALT 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
TgeneGALT

GO:0006011

UDP-glucose metabolic process

27005423

TgeneGALT

GO:0006012

galactose metabolic process

27005423



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/chr8:144351690/chr9:34649406)
- 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 GLI4 (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 GALT (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)
ENST00000521682GLI4chr8144351690+ENST00000450095GALTchr934649406+52520985444119
ENST00000340042GLI4chr8144351690+ENST00000450095GALTchr934649406+52520985444119
ENST00000344692GLI4chr8144351690+ENST00000450095GALTchr934649406+47916339398119
ENST00000517468GLI4chr8144351690+ENST00000450095GALTchr934649406+47916339398119
ENST00000523522GLI4chr8144351690+ENST00000450095GALTchr934649406+47916339398119

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
ENST00000521682ENST00000450095GLI4chr8144351690+GALTchr934649406+0.0738748240.9261252
ENST00000340042ENST00000450095GLI4chr8144351690+GALTchr934649406+0.0738748240.9261252
ENST00000344692ENST00000450095GLI4chr8144351690+GALTchr934649406+0.1223023160.8776977
ENST00000517468ENST00000450095GLI4chr8144351690+GALTchr934649406+0.1223023160.8776977
ENST00000523522ENST00000450095GLI4chr8144351690+GALTchr934649406+0.1223023160.8776977

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 GLI4-GALT

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GLI4chr8144351690GALTchr93464940616341HHEPQLHLHGHQHGAPTGSEAGANWN
GLI4chr8144351690GALTchr93464940620941HHEPQLHLHGHQHGAPTGSEAGANWN

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Potential FusionNeoAntigen Information of GLI4-GALT 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.
GLI4-GALT_144351690_34649406.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)
GLI4-GALTchr8144351690chr934649406209HLA-B08:09HLHGHQHGA0.84090.7954615
GLI4-GALTchr8144351690chr934649406209HLA-B39:06LHLHGHQHGA0.98950.9314515
GLI4-GALTchr8144351690chr934649406209HLA-B39:06QHGAPTGSEA0.98290.90721121
GLI4-GALTchr8144351690chr934649406209HLA-A02:03HLHGHQHGA0.97950.6605615

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Potential FusionNeoAntigen Information of GLI4-GALT 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.
GLI4-GALT_144351690_34649406.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)
GLI4-GALTchr8144351690chr934649406209DRB1-1141EPQLHLHGHQHGAPT217
GLI4-GALTchr8144351690chr934649406209DRB1-1155EPQLHLHGHQHGAPT217

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Fusion breakpoint peptide structures of GLI4-GALT

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
3401HLHGHQHGAPTGSEGLI4GALTchr8144351690chr934649406209

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GLI4-GALT

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-B14:023BVN3401HLHGHQHGAPTGSE-6.9888-7.1022
HLA-B14:023BVN3401HLHGHQHGAPTGSE-3.71338-4.74868
HLA-B52:013W393401HLHGHQHGAPTGSE-5.59342-6.62872
HLA-B52:013W393401HLHGHQHGAPTGSE-5.47943-5.59283
HLA-A24:025HGA3401HLHGHQHGAPTGSE-6.88714-7.00054
HLA-A24:025HGA3401HLHGHQHGAPTGSE-6.46973-7.50503
HLA-B44:053DX83401HLHGHQHGAPTGSE-6.00524-6.11864
HLA-B44:053DX83401HLHGHQHGAPTGSE-5.7663-6.8016

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Vaccine Design for the FusionNeoAntigens of GLI4-GALT

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
GLI4-GALTchr8144351690chr9346494061121QHGAPTGSEAAACATGGGGCTCCCACAGGATCAGAGGCTG
GLI4-GALTchr8144351690chr934649406515LHLHGHQHGATTCACCTCCATGGGCATCAACATGGGGCTC
GLI4-GALTchr8144351690chr934649406615HLHGHQHGAACCTCCATGGGCATCAACATGGGGCTC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
GLI4-GALTchr8144351690chr934649406217EPQLHLHGHQHGAPTAGCCTCAGCTTCACCTCCATGGGCATCAACATGGGGCTCCCACAG

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Information of the samples that have these potential fusion neoantigens of GLI4-GALT

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
ESCAGLI4-GALTchr8144351690ENST00000340042chr934649406ENST00000450095TCGA-L5-A43H

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Potential target of CAR-T therapy development for GLI4-GALT

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 GLI4-GALT

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 GLI4-GALT

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