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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:HMGN2-TPM2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HMGN2-TPM2
FusionPDB ID: 36957
FusionGDB2.0 ID: 36957
HgeneTgene
Gene symbol

HMGN2

TPM2

Gene ID

3151

7169

Gene namehigh mobility group nucleosomal binding domain 2tropomyosin 2
SynonymsHMG17AMCD1|DA1|DA2B|DA2B4|HEL-S-273|NEM4|TMSB
Cytomap

1p36.11

9p13.3

Type of geneprotein-codingprotein-coding
Descriptionnon-histone chromosomal protein HMG-17high mobility group nucleosome-binding domain-containing protein 2high mobility group protein N2high-mobility group (nonhistone chromosomal) protein 17nonhistone chromosomal protein HMG-17tropomyosin beta chainepididymis secretory protein Li 273nemaline myopathy type 4tropomyosin 2 (beta)
Modification date2020031320200328
UniProtAcc

Q86SG4

Main function of 5'-partner protein:
.
Ensembl transtripts involved in fusion geneENST idsENST00000493418, ENST00000361427, 
ENST00000329305, ENST00000360958, 
ENST00000378292, ENST00000378300, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 4 X 4=14417 X 13 X 5=1105
# samples 817
** MAII scorelog2(8/144*10)=-0.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(17/1105*10)=-2.70043971814109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HMGN2 [Title/Abstract] AND TPM2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HMGN2 [Title/Abstract] AND TPM2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HMGN2(26800018)-TPM2(35684312), # samples:1
Anticipated loss of major functional domain due to fusion event.
* 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
TgeneTPM2

GO:0043462

regulation of ATPase activity

17194691



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/chr1:26800018/chr9:35684312)
- 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 HMGN2 (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 TPM2 (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)
ENST00000361427HMGN2chr126800018+ENST00000378300TPM2chr935684312-11371545150172
ENST00000361427HMGN2chr126800018+ENST00000378292TPM2chr935684312-3961549430670
ENST00000361427HMGN2chr126800018+ENST00000329305TPM2chr935684312-3741549430670
ENST00000361427HMGN2chr126800018+ENST00000360958TPM2chr935684312-53615430352774

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
ENST00000361427ENST00000378300HMGN2chr126800018+TPM2chr935684312-0.183682260.8163178
ENST00000361427ENST00000378292HMGN2chr126800018+TPM2chr935684312-0.08583910.91416085
ENST00000361427ENST00000329305HMGN2chr126800018+TPM2chr935684312-0.0959568840.90404314
ENST00000361427ENST00000360958HMGN2chr126800018+TPM2chr935684312-0.0131829620.98681706

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 HMGN2-TPM2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HMGN2chr126800018TPM2chr93568431215420GDAKGDKAKVKDEAETRAEFAERSVA

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Potential FusionNeoAntigen Information of HMGN2-TPM2 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.
HMGN2-TPM2_26800018_35684312.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)
HMGN2-TPM2chr126800018chr935684312154HLA-B18:01DEAETRAEF0.99940.96651120
HMGN2-TPM2chr126800018chr935684312154HLA-B44:03DEAETRAEF0.99880.97011120
HMGN2-TPM2chr126800018chr935684312154HLA-B15:37DEAETRAEF0.71180.75741120
HMGN2-TPM2chr126800018chr935684312154HLA-B47:01KDEAETRAEF0.98780.59481020
HMGN2-TPM2chr126800018chr935684312154HLA-B45:01DEAETRAEFA0.97710.85751121
HMGN2-TPM2chr126800018chr935684312154HLA-B44:03KDEAETRAEF0.93240.97651020
HMGN2-TPM2chr126800018chr935684312154HLA-B50:02DEAETRAEFA0.91040.54551121
HMGN2-TPM2chr126800018chr935684312154HLA-B18:01KDEAETRAEF0.48570.96241020
HMGN2-TPM2chr126800018chr935684312154HLA-A33:05EAETRAEFAER0.99680.52041223
HMGN2-TPM2chr126800018chr935684312154HLA-A33:01EAETRAEFAER0.99680.52041223
HMGN2-TPM2chr126800018chr935684312154HLA-B18:04DEAETRAEF0.99960.97341120
HMGN2-TPM2chr126800018chr935684312154HLA-B18:07DEAETRAEF0.99950.94261120
HMGN2-TPM2chr126800018chr935684312154HLA-B18:08DEAETRAEF0.99940.95931120
HMGN2-TPM2chr126800018chr935684312154HLA-B18:05DEAETRAEF0.99940.96651120
HMGN2-TPM2chr126800018chr935684312154HLA-B18:06DEAETRAEF0.99930.97041120
HMGN2-TPM2chr126800018chr935684312154HLA-B18:03DEAETRAEF0.9990.9641120
HMGN2-TPM2chr126800018chr935684312154HLA-B44:07DEAETRAEF0.99880.97011120
HMGN2-TPM2chr126800018chr935684312154HLA-B44:26DEAETRAEF0.99880.97011120
HMGN2-TPM2chr126800018chr935684312154HLA-B44:13DEAETRAEF0.99880.97011120
HMGN2-TPM2chr126800018chr935684312154HLA-B18:11DEAETRAEF0.99320.93481120
HMGN2-TPM2chr126800018chr935684312154HLA-B40:04DEAETRAEF0.96010.72481120
HMGN2-TPM2chr126800018chr935684312154HLA-B35:20DEAETRAEF0.78640.95921120
HMGN2-TPM2chr126800018chr935684312154HLA-B41:03DEAETRAEF0.54920.56061120
HMGN2-TPM2chr126800018chr935684312154HLA-B15:53DEAETRAEF0.22950.92361120
HMGN2-TPM2chr126800018chr935684312154HLA-B48:02KDEAETRAEF0.98870.96791020
HMGN2-TPM2chr126800018chr935684312154HLA-B15:53KDEAETRAEF0.98690.95011020
HMGN2-TPM2chr126800018chr935684312154HLA-B44:13KDEAETRAEF0.93240.97651020
HMGN2-TPM2chr126800018chr935684312154HLA-B44:26KDEAETRAEF0.93240.97651020
HMGN2-TPM2chr126800018chr935684312154HLA-B44:07KDEAETRAEF0.93240.97651020
HMGN2-TPM2chr126800018chr935684312154HLA-B18:05KDEAETRAEF0.48570.96241020
HMGN2-TPM2chr126800018chr935684312154HLA-B18:03KDEAETRAEF0.48160.9591020

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Potential FusionNeoAntigen Information of HMGN2-TPM2 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 HMGN2-TPM2

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
4105KAKVKDEAETRAEFHMGN2TPM2chr126800018chr935684312154

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HMGN2-TPM2

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-B14:023BVN4105KAKVKDEAETRAEF-7.86699-7.98039
HLA-B14:023BVN4105KAKVKDEAETRAEF-5.17617-6.21147
HLA-B52:013W394105KAKVKDEAETRAEF-6.45508-6.56848
HLA-B52:013W394105KAKVKDEAETRAEF-4.28574-5.32104
HLA-A11:014UQ24105KAKVKDEAETRAEF-9.00881-9.12221
HLA-A24:025HGA4105KAKVKDEAETRAEF-8.29865-8.41205
HLA-A24:025HGA4105KAKVKDEAETRAEF-4.23297-5.26827
HLA-B44:053DX84105KAKVKDEAETRAEF-7.41059-7.52399
HLA-B44:053DX84105KAKVKDEAETRAEF-4.31231-5.34761

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Vaccine Design for the FusionNeoAntigens of HMGN2-TPM2

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
HMGN2-TPM2chr126800018chr9356843121020KDEAETRAEFAAGGACGAAGCTGAGACCCGAGCAGAGTTT
HMGN2-TPM2chr126800018chr9356843121120DEAETRAEFGACGAAGCTGAGACCCGAGCAGAGTTT
HMGN2-TPM2chr126800018chr9356843121121DEAETRAEFAGACGAAGCTGAGACCCGAGCAGAGTTTGCC
HMGN2-TPM2chr126800018chr9356843121223EAETRAEFAERGAAGCTGAGACCCGAGCAGAGTTTGCCGAGAGG

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 HMGN2-TPM2

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
STADHMGN2-TPM2chr126800018ENST00000361427chr935684312ENST00000329305TCGA-BR-A4J5-01A

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Potential target of CAR-T therapy development for HMGN2-TPM2

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 HMGN2-TPM2

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 HMGN2-TPM2

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