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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:PRUNE-ARNT

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PRUNE-ARNT
FusionPDB ID: 69361
FusionGDB2.0 ID: 69361
HgeneTgene
Gene symbol

PRUNE

ARNT

Gene ID

58497

375056

Gene nameprune exopolyphosphatase 1MIA SH3 domain ER export factor 3
SynonymsDRES-17|DRES17|H-PRUNE|HTCD37|NMIHBA|PRUNEARNT|D320|TANGO|TANGO1|UNQ6077
Cytomap

1q21.3

1q41

Type of geneprotein-codingprotein-coding
Descriptionexopolyphosphatase PRUNE1Drosophila-related expressed sequence 17protein prune homologprotein prune homolog 1transport and Golgi organization protein 1 homologC219-reactive peptideMIA family member 3, ER export factormelanoma inhibitory activity family, member 3melanoma inhibitory activity protein 3transport and Golgi organization protein 1
Modification date2020031320200313
UniProtAcc.

Q8WYA1

Main function of 5'-partner protein: FUNCTION: Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. {ECO:0000269|PubMed:11018023, ECO:0000269|PubMed:12738229, ECO:0000269|PubMed:14672706}.
Ensembl transtripts involved in fusion geneENST idsENST00000467771, ENST00000271620, 
ENST00000271619, ENST00000368934, 
ENST00000368935, ENST00000368936, 
ENST00000368937, 
ENST00000354396, 
ENST00000358595, ENST00000505755, 
ENST00000515192, ENST00000468970, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 5 X 6=2109 X 6 X 6=324
# samples 89
** MAII scorelog2(8/210*10)=-1.39231742277876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/324*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PRUNE [Title/Abstract] AND ARNT [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PRUNE [Title/Abstract] AND ARNT [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRUNE(150991145)-ARNT(150812130), # samples:1
Anticipated loss of major functional domain due to fusion event.PRUNE-ARNT 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.
PRUNE-ARNT 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.
PRUNE-ARNT 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.
PRUNE-ARNT 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
TgeneARNT

GO:0002687

positive regulation of leukocyte migration

17726152

TgeneARNT

GO:0007162

negative regulation of cell adhesion

17726152

TgeneARNT

GO:0030336

negative regulation of cell migration

17044017

TgeneARNT

GO:0042060

wound healing

17044017



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/chr1:150991145/chr1:150812130)
- 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 PRUNE (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 ARNT (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)
ENST00000271620PRUNEchr1150991145+ENST00000358595ARNTchr1150812130-4905491602588842
ENST00000271620PRUNEchr1150991145+ENST00000354396ARNTchr1150812130-3745491602582840
ENST00000271620PRUNEchr1150991145+ENST00000515192ARNTchr1150812130-2914491602573837
ENST00000271620PRUNEchr1150991145+ENST00000505755ARNTchr1150812130-2649491602588842

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
ENST00000271620ENST00000358595PRUNEchr1150991145+ARNTchr1150812130-0.0010342560.99896574
ENST00000271620ENST00000354396PRUNEchr1150991145+ARNTchr1150812130-0.0022165680.9977835
ENST00000271620ENST00000515192PRUNEchr1150991145+ARNTchr1150812130-0.0048479420.995152
ENST00000271620ENST00000505755PRUNEchr1150991145+ARNTchr1150812130-0.0078701840.99212974

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 PRUNE-ARNT

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PRUNEchr1150991145ARNTchr1150812130491139YQAGQLTLILVDHHILSKENHSEIER

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Potential FusionNeoAntigen Information of PRUNE-ARNT 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.
PRUNE-ARNT_150991145_150812130.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)
PRUNE-ARNTchr1150991145chr1150812130491HLA-A02:35TLILVDHHI0.88560.5061615
PRUNE-ARNTchr1150991145chr1150812130491HLA-B15:18HHILSKENH0.26990.5281221

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Potential FusionNeoAntigen Information of PRUNE-ARNT 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.
PRUNE-ARNT_150991145_150812130.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)
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0301LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0313LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0318LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0320LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0322LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0324LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0326LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0328LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0330LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0332LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0334LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0336LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0342LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0344LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0346LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0348LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0350LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0352LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0354LTLILVDHHILSKEN520
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0437DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0801DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0803DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0806DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0806VDHHILSKENHSEIE1025
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0808DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0810DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0810VDHHILSKENHSEIE1025
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0810LVDHHILSKENHSEI924
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0811DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0812DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0812VDHHILSKENHSEIE1025
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0814DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0816DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0822DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0822VDHHILSKENHSEIE1025
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0823DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0826DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0827DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0833DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0835DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0836DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0838DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-0839DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-1332DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-1348DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-1431QLTLILVDHHILSKE419
PRUNE-ARNTchr1150991145chr1150812130491DRB1-1439QLTLILVDHHILSKE419
PRUNE-ARNTchr1150991145chr1150812130491DRB1-1455QLTLILVDHHILSKE419
PRUNE-ARNTchr1150991145chr1150812130491DRB1-1457DHHILSKENHSEIER1126
PRUNE-ARNTchr1150991145chr1150812130491DRB1-1457VDHHILSKENHSEIE1025
PRUNE-ARNTchr1150991145chr1150812130491DRB1-1457LVDHHILSKENHSEI924
PRUNE-ARNTchr1150991145chr1150812130491DRB1-1478DHHILSKENHSEIER1126

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Fusion breakpoint peptide structures of PRUNE-ARNT

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
9461TLILVDHHILSKENPRUNEARNTchr1150991145chr1150812130491

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PRUNE-ARNT

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-B14:023BVN9461TLILVDHHILSKEN-7.33537-7.45267
HLA-B14:023BVN9461TLILVDHHILSKEN-6.76001-7.79921
HLA-B52:013W399461TLILVDHHILSKEN-6.07283-6.19013
HLA-B52:013W399461TLILVDHHILSKEN-5.27422-6.31342
HLA-A11:014UQ29461TLILVDHHILSKEN-7.62346-7.74076
HLA-A24:025HGA9461TLILVDHHILSKEN-8.38572-8.50302
HLA-A24:025HGA9461TLILVDHHILSKEN-4.93038-5.96958
HLA-B27:056PYJ9461TLILVDHHILSKEN-3.63989-4.67909
HLA-B44:053DX89461TLILVDHHILSKEN-5.85539-5.97269
HLA-B44:053DX89461TLILVDHHILSKEN-3.30708-4.34628

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Vaccine Design for the FusionNeoAntigens of PRUNE-ARNT

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
PRUNE-ARNTchr1150991145chr11508121301221HHILSKENHCAAGGAAAATCACAGTGAAATTGAACG
PRUNE-ARNTchr1150991145chr1150812130615TLILVDHHICGACCATCATATCTTATCCAAGGAAAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PRUNE-ARNTchr1150991145chr11508121301025VDHHILSKENHSEIECTTATCCAAGGAAAATCACAGTGAAATTGAACGGCGGCGACGGAA
PRUNE-ARNTchr1150991145chr11508121301126DHHILSKENHSEIERATCCAAGGAAAATCACAGTGAAATTGAACGGCGGCGACGGAACAA
PRUNE-ARNTchr1150991145chr1150812130419QLTLILVDHHILSKECCTTGTCGACCATCATATCTTATCCAAGGAAAATCACAGTGAAAT
PRUNE-ARNTchr1150991145chr1150812130520LTLILVDHHILSKENTGTCGACCATCATATCTTATCCAAGGAAAATCACAGTGAAATTGA
PRUNE-ARNTchr1150991145chr1150812130924LVDHHILSKENHSEITATCTTATCCAAGGAAAATCACAGTGAAATTGAACGGCGGCGACG

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Information of the samples that have these potential fusion neoantigens of PRUNE-ARNT

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
STADPRUNE-ARNTchr1150991145ENST00000271620chr1150812130ENST00000354396TCGA-BR-8284-01A

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Potential target of CAR-T therapy development for PRUNE-ARNT

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 PRUNE-ARNT

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 PRUNE-ARNT

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