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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:UTRN-HMGA2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: UTRN-HMGA2
FusionPDB ID: 97745
FusionGDB2.0 ID: 97745
HgeneTgene
Gene symbol

UTRN

HMGA2

Gene ID

7402

8091

Gene nameutrophinhigh mobility group AT-hook 2
SynonymsDMDL|DRP|DRP1BABL|HMGI-C|HMGIC|LIPO|STQTL9
Cytomap

6q24.2

12q14.3

Type of geneprotein-codingprotein-coding
DescriptionutrophinDRP-1dystrophin-related protein 1high mobility group protein HMGI-CHMGA2/KRT121P fusionhigh-mobility group (nonhistone chromosomal) protein isoform I-C
Modification date2020031320200329
UniProtAcc.

P52926

Main function of 5'-partner protein: FUNCTION: Functions as a transcriptional regulator. Functions in cell cycle regulation through CCNA2. Plays an important role in chromosome condensation during the meiotic G2/M transition of spermatocytes. Plays a role in postnatal myogenesis, is involved in satellite cell activation (By similarity). Positively regulates IGF2 expression through PLAG1 and in a PLAG1-independent manner (PubMed:28796236). {ECO:0000250|UniProtKB:P52927, ECO:0000269|PubMed:14645522, ECO:0000269|PubMed:28796236}.
Ensembl transtripts involved in fusion geneENST idsENST00000367526, ENST00000367545, 
ENST00000480333, 
ENST00000354636, 
ENST00000393577, ENST00000393578, 
ENST00000403681, ENST00000425208, 
ENST00000536545, ENST00000541363, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score34 X 28 X 11=1047216 X 12 X 5=960
# samples 3715
** MAII scorelog2(37/10472*10)=-4.82286792142893
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/960*10)=-2.67807190511264
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: UTRN [Title/Abstract] AND HMGA2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: UTRN [Title/Abstract] AND HMGA2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)UTRN(145021379)-HMGA2(66232299), # samples:2
Anticipated loss of major functional domain due to fusion event.UTRN-HMGA2 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.
UTRN-HMGA2 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.
UTRN-HMGA2 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.
UTRN-HMGA2 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
TgeneHMGA2

GO:0000122

negative regulation of transcription by RNA polymerase II

14627817

TgeneHMGA2

GO:0002062

chondrocyte differentiation

21484705

TgeneHMGA2

GO:0006284

base-excision repair

19465398

TgeneHMGA2

GO:0007095

mitotic G2 DNA damage checkpoint

16061642

TgeneHMGA2

GO:0010564

regulation of cell cycle process

14645522

TgeneHMGA2

GO:0010628

positive regulation of gene expression

18832382

TgeneHMGA2

GO:0031052

chromosome breakage

19549901

TgeneHMGA2

GO:0031507

heterochromatin assembly

16901784

TgeneHMGA2

GO:0035978

histone H2A-S139 phosphorylation

16061642

TgeneHMGA2

GO:0035986

senescence-associated heterochromatin focus assembly

16901784

TgeneHMGA2

GO:0035988

chondrocyte proliferation

21484705

TgeneHMGA2

GO:0042769

DNA damage response, detection of DNA damage

19465398

TgeneHMGA2

GO:0043065

positive regulation of apoptotic process

16061642

TgeneHMGA2

GO:0043066

negative regulation of apoptotic process

19465398

TgeneHMGA2

GO:0043392

negative regulation of DNA binding

14645522

TgeneHMGA2

GO:0043922

negative regulation by host of viral transcription

17005673

TgeneHMGA2

GO:0045869

negative regulation of single stranded viral RNA replication via double stranded DNA intermediate

17005673

TgeneHMGA2

GO:0045892

negative regulation of transcription, DNA-templated

18832382

TgeneHMGA2

GO:0045893

positive regulation of transcription, DNA-templated

15225648|15755872|17005673|17324944|17426251

TgeneHMGA2

GO:0045944

positive regulation of transcription by RNA polymerase II

14645522|18832382

TgeneHMGA2

GO:0071158

positive regulation of cell cycle arrest

16061642

TgeneHMGA2

GO:0071902

positive regulation of protein serine/threonine kinase activity

19549901

TgeneHMGA2

GO:0090402

oncogene-induced cell senescence

16901784

TgeneHMGA2

GO:2000648

positive regulation of stem cell proliferation

21484705

TgeneHMGA2

GO:2000679

positive regulation of transcription regulatory region DNA binding

18832382

TgeneHMGA2

GO:2000685

positive regulation of cellular response to X-ray

16061642

TgeneHMGA2

GO:2001022

positive regulation of response to DNA damage stimulus

16061642|19465398

TgeneHMGA2

GO:2001033

negative regulation of double-strand break repair via nonhomologous end joining

19549901

TgeneHMGA2

GO:2001038

regulation of cellular response to drug

16061642



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/chr6:145021379/chr12:66232299)
- 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 UTRN (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 HMGA2 (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)
ENST00000367545UTRNchr6145021379+ENST00000403681HMGA2chr1266232299+109447809079402646
ENST00000367545UTRNchr6145021379+ENST00000541363HMGA2chr1266232299+153327809079102636
ENST00000367545UTRNchr6145021379+ENST00000393577HMGA2chr1266232299+80747809079672655
ENST00000367545UTRNchr6145021379+ENST00000393578HMGA2chr1266232299+81987809078832627
ENST00000367545UTRNchr6145021379+ENST00000425208HMGA2chr1266232299+82447809078892629
ENST00000367545UTRNchr6145021379+ENST00000536545HMGA2chr1266232299+85887809080542684
ENST00000367545UTRNchr6145021379+ENST00000354636HMGA2chr1266232299+83297809079312643
ENST00000367526UTRNchr6145021379+ENST00000403681HMGA2chr1266232299+3856721247852201
ENST00000367526UTRNchr6145021379+ENST00000541363HMGA2chr1266232299+8244721247822191
ENST00000367526UTRNchr6145021379+ENST00000393577HMGA2chr1266232299+986721247879210
ENST00000367526UTRNchr6145021379+ENST00000393578HMGA2chr1266232299+1110721247795182
ENST00000367526UTRNchr6145021379+ENST00000425208HMGA2chr1266232299+1156721247801184
ENST00000367526UTRNchr6145021379+ENST00000536545HMGA2chr1266232299+1500721247966239
ENST00000367526UTRNchr6145021379+ENST00000354636HMGA2chr1266232299+1241721247843198

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
ENST00000367545ENST00000403681UTRNchr6145021379+HMGA2chr1266232299+0.0007693350.9992306
ENST00000367545ENST00000541363UTRNchr6145021379+HMGA2chr1266232299+0.0005558990.99944407
ENST00000367545ENST00000393577UTRNchr6145021379+HMGA2chr1266232299+0.0022766840.9977233
ENST00000367545ENST00000393578UTRNchr6145021379+HMGA2chr1266232299+0.0015581590.9984419
ENST00000367545ENST00000425208UTRNchr6145021379+HMGA2chr1266232299+0.0020409360.997959
ENST00000367545ENST00000536545UTRNchr6145021379+HMGA2chr1266232299+0.0021994150.9978005
ENST00000367545ENST00000354636UTRNchr6145021379+HMGA2chr1266232299+0.0015049730.998495
ENST00000367526ENST00000403681UTRNchr6145021379+HMGA2chr1266232299+0.000656830.9993431
ENST00000367526ENST00000541363UTRNchr6145021379+HMGA2chr1266232299+0.0010945590.9989054
ENST00000367526ENST00000393577UTRNchr6145021379+HMGA2chr1266232299+0.0012300060.99876994
ENST00000367526ENST00000393578UTRNchr6145021379+HMGA2chr1266232299+0.0018393030.99816066
ENST00000367526ENST00000425208UTRNchr6145021379+HMGA2chr1266232299+0.0031724410.99682754
ENST00000367526ENST00000536545UTRNchr6145021379+HMGA2chr1266232299+0.0191551220.98084486
ENST00000367526ENST00000354636UTRNchr6145021379+HMGA2chr1266232299+0.0025576050.99744236

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 UTRN-HMGA2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
UTRNchr6145021379HMGA2chr1266232299721158DVPALQLQYDHCKKAEATGEKRPRGR
UTRNchr6145021379HMGA2chr126623229978092603DVPALQLQYDHCKKAEATGEKRPRGR

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Potential FusionNeoAntigen Information of UTRN-HMGA2 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.
UTRN-HMGA2_145021379_66232299.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)
UTRN-HMGA2chr6145021379chr1266232299721HLA-B15:04LQYDHCKKA0.68720.8855615

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Potential FusionNeoAntigen Information of UTRN-HMGA2 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 UTRN-HMGA2

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
5502LQYDHCKKAEATGEUTRNHMGA2chr6145021379chr1266232299721

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of UTRN-HMGA2

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-B14:023BVN5502LQYDHCKKAEATGE-7.15543-7.26883
HLA-B14:023BVN5502LQYDHCKKAEATGE-4.77435-5.80965
HLA-B52:013W395502LQYDHCKKAEATGE-6.80875-6.92215
HLA-B52:013W395502LQYDHCKKAEATGE-4.20386-5.23916
HLA-A11:014UQ25502LQYDHCKKAEATGE-7.5194-8.5547
HLA-A11:014UQ25502LQYDHCKKAEATGE-6.9601-7.0735
HLA-A24:025HGA5502LQYDHCKKAEATGE-7.52403-7.63743
HLA-A24:025HGA5502LQYDHCKKAEATGE-5.82433-6.85963
HLA-B27:056PYJ5502LQYDHCKKAEATGE-3.28285-4.31815
HLA-B44:053DX85502LQYDHCKKAEATGE-5.91172-6.94702
HLA-B44:053DX85502LQYDHCKKAEATGE-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of UTRN-HMGA2

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
UTRN-HMGA2chr6145021379chr1266232299615LQYDHCKKACTCCAGTATGACCATTGTAAGAAAGCA

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 UTRN-HMGA2

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
SARCUTRN-HMGA2chr6145021379ENST00000367526chr1266232299ENST00000354636TCGA-IF-A3RQ-01A

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Potential target of CAR-T therapy development for UTRN-HMGA2

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 UTRN-HMGA2

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 UTRN-HMGA2

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
TgeneHMGA2C1519176Salivary Gland Pleomorphic Adenoma2ORPHANET
TgeneHMGA2C0005612Birth Weight1CTD_human
TgeneHMGA2C0006826Malignant Neoplasms1CTD_human
TgeneHMGA2C0027626Neoplasm Invasiveness1CTD_human
TgeneHMGA2C0027651Neoplasms1CTD_human
TgeneHMGA2C0086692Benign Neoplasm1CTD_human
TgeneHMGA2C0175693Russell-Silver syndrome1GENOMICS_ENGLAND
TgeneHMGA2C0473935Radiolabeled somatostatin analog study1GENOMICS_ENGLAND
TgeneHMGA2C0796160MENTAL RETARDATION, X-LINKED, SNYDER-ROBINSON TYPE1GENOMICS_ENGLAND
TgeneHMGA2C1096309Myolipoma1GENOMICS_ENGLAND
TgeneHMGA2C430514012q14 microdeletion syndrome1ORPHANET