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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:GOLPH3-IKZF3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GOLPH3-IKZF3
FusionPDB ID: 33968
FusionGDB2.0 ID: 33968
HgeneTgene
Gene symbol

GOLPH3

IKZF3

Gene ID

64083

22806

Gene namegolgi phosphoprotein 3IKAROS family zinc finger 3
SynonymsGOPP1|GPP34|MIDAS|Vps74AIO|AIOLOS|ZNFN1A3
Cytomap

5p13.3

17q12-q21.1

Type of geneprotein-codingprotein-coding
DescriptionGolgi phosphoprotein 3coat protein GPP34coat-proteingolgi peripheral membrane protein 1, 34 kDagolgi proteingolgi-associated proteinmitochondrial DNA absence factorzinc finger protein Aioloszinc finger DNA binding protein Aioloszinc finger protein, subfamily 1A, 3 (Aiolos)
Modification date2020032920200327
UniProtAcc

Q9H4A5

Main function of 5'-partner protein: FUNCTION: Phosphatidylinositol-4-phosphate-binding protein that may antagonize the action of GOLPH3 which is required for the process of vesicle budding at the Golgi and anterograde transport to the plasma membrane. {ECO:0000269|PubMed:23345592}.

Q9UKT9

Main function of 5'-partner protein: FUNCTION: Transcription factor that plays an important role in the regulation of lymphocyte differentiation. Plays an essential role in regulation of B-cell differentiation, proliferation and maturation to an effector state. Involved in regulating BCL2 expression and controlling apoptosis in T-cells in an IL2-dependent manner. {ECO:0000269|PubMed:10369681}.
Ensembl transtripts involved in fusion geneENST idsENST00000265070, ENST00000512668, 
ENST00000583368, ENST00000346243, 
ENST00000350532, ENST00000351680, 
ENST00000377944, ENST00000377945, 
ENST00000377952, ENST00000377958, 
ENST00000394189, ENST00000439016, 
ENST00000439167, ENST00000467757, 
ENST00000535189, ENST00000346872, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 10 X 7=77034 X 12 X 14=5712
# samples 1649
** MAII scorelog2(16/770*10)=-2.2667865406949
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(49/5712*10)=-3.54314232502653
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GOLPH3 [Title/Abstract] AND IKZF3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GOLPH3 [Title/Abstract] AND IKZF3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GOLPH3(32173916)-IKZF3(37944627), # samples:3
Anticipated loss of major functional domain due to fusion event.GOLPH3-IKZF3 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.
GOLPH3-IKZF3 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.
GOLPH3-IKZF3 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.
GOLPH3-IKZF3 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.
GOLPH3-IKZF3 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
GOLPH3-IKZF3 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
GOLPH3-IKZF3 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF.
GOLPH3-IKZF3 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted 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
HgeneGOLPH3

GO:0010821

regulation of mitochondrion organization

16263763



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/chr5:32173916/chr17:37944627)
- 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 GOLPH3 (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 IKZF3 (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)
ENST00000265070GOLPH3chr532173915-ENST00000346243IKZF3chr1737922746-12455411171244375
ENST00000265070GOLPH3chr532173915-ENST00000350532IKZF3chr1737922746-12455411171244375
ENST00000265070GOLPH3chr532173915-ENST00000351680IKZF3chr1737922746-12455411171244375
ENST00000265070GOLPH3chr532173915-ENST00000467757IKZF3chr1737922746-12455411171244375
ENST00000265070GOLPH3chr532173916-ENST00000346243IKZF3chr1737922746-12455411171244375
ENST00000265070GOLPH3chr532173916-ENST00000350532IKZF3chr1737922746-12455411171244375
ENST00000265070GOLPH3chr532173916-ENST00000351680IKZF3chr1737922746-12455411171244375
ENST00000265070GOLPH3chr532173916-ENST00000467757IKZF3chr1737922746-12455411171244375

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
ENST00000265070ENST00000346243GOLPH3chr532173915-IKZF3chr1737922746-0.0015420170.998458
ENST00000265070ENST00000350532GOLPH3chr532173915-IKZF3chr1737922746-0.0015420170.998458
ENST00000265070ENST00000351680GOLPH3chr532173915-IKZF3chr1737922746-0.0015420170.998458
ENST00000265070ENST00000467757GOLPH3chr532173915-IKZF3chr1737922746-0.0015420170.998458
ENST00000265070ENST00000346243GOLPH3chr532173916-IKZF3chr1737922746-0.0015420170.998458
ENST00000265070ENST00000350532GOLPH3chr532173916-IKZF3chr1737922746-0.0015420170.998458
ENST00000265070ENST00000351680GOLPH3chr532173916-IKZF3chr1737922746-0.0015420170.998458
ENST00000265070ENST00000467757GOLPH3chr532173916-IKZF3chr1737922746-0.0015420170.998458

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 GOLPH3-IKZF3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GOLPH3chr532173915IKZF3chr173792274654189PGAAAHRGLPQRRRQGAGGGRRRRQQ
GOLPH3chr532173916IKZF3chr173792274654189PGAAAHRGLPQRRRQGAGGGRRRRQQ

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Potential FusionNeoAntigen Information of GOLPH3-IKZF3 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.
GOLPH3-IKZF3_32173915_37922746.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)
GOLPH3-IKZF3chr532173915chr1737922746541HLA-B08:09LPQRRRQGA0.97760.6563817
GOLPH3-IKZF3chr532173915chr1737922746541HLA-B27:10RRQGAGGGR0.98790.69961221

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Potential FusionNeoAntigen Information of GOLPH3-IKZF3 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 GOLPH3-IKZF3

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
7872RGLPQRRRQGAGGGGOLPH3IKZF3chr532173915chr1737922746541

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GOLPH3-IKZF3

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-B14:023BVN7872RGLPQRRRQGAGGG-7.19905-7.31085
HLA-B14:023BVN7872RGLPQRRRQGAGGG-4.95643-5.99953
HLA-B52:013W397872RGLPQRRRQGAGGG-5.83545-5.94725
HLA-B52:013W397872RGLPQRRRQGAGGG-5.05006-6.09316
HLA-A24:025HGA7872RGLPQRRRQGAGGG-7.70134-7.81314
HLA-A24:025HGA7872RGLPQRRRQGAGGG-3.44118-4.48428
HLA-B27:056PYJ7872RGLPQRRRQGAGGG-9.10792-9.21972
HLA-B44:053DX87872RGLPQRRRQGAGGG-4.82059-4.93239
HLA-B44:053DX87872RGLPQRRRQGAGGG-3.88198-4.92508
HLA-A02:016TDR7872RGLPQRRRQGAGGG-2.45382-2.56562

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Vaccine Design for the FusionNeoAntigens of GOLPH3-IKZF3

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
GOLPH3-IKZF3chr532173915chr17379227461221RRQGAGGGRGAGGTGAGAAGCGCCACTGCTTTGATG
GOLPH3-IKZF3chr532173915chr1737922746817LPQRRRQGACTCAAGGACCGCGAGGTGAGAAGCGCC

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 GOLPH3-IKZF3

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
ESCAGOLPH3-IKZF3chr532173915ENST00000265070chr1737922746ENST00000346243TCGA-L5-A8NI

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Potential target of CAR-T therapy development for GOLPH3-IKZF3

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 GOLPH3-IKZF3

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 GOLPH3-IKZF3

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