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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:HIVEP3-FOXO3 (FusionGDB2 ID:36417)

Fusion Gene Summary for HIVEP3-FOXO3

check button Fusion gene summary
Fusion gene informationFusion gene name: HIVEP3-FOXO3
Fusion gene ID: 36417
HgeneTgene
Gene symbol

HIVEP3

FOXO3

Gene ID

59269

2309

Gene nameHIVEP zinc finger 3forkhead box O3
SynonymsKBP-1|KBP1|KRC|SHN3|Schnurri-3|ZAS3|ZNF40CAF6q21|FKHRL1|FKHRL1P2|FOXO2|FOXO3A
Cytomap

1p34.2

6q21

Type of geneprotein-codingprotein-coding
Descriptiontranscription factor HIVEP3ZAS family, member 3human immunodeficiency virus type I enhancer binding protein 3kappa-B and V(D)J recombination signal sequences-binding proteinkappa-binding protein 1zinc finger protein ZAS3forkhead box protein O3forkhead box O3Aforkhead homolog (rhabdomyosarcoma) like 1forkhead in rhabdomyosarcoma-like 1forkhead, Drosophila, homolog of, in rhabdomyosarcoma-like 1
Modification date2020031320200329
UniProtAcc

Q5T1R4

O43524

Ensembl transtripts involved in fusion geneENST00000372583, ENST00000372584, 
ENST00000247584, ENST00000429157, 
ENST00000460604, 
ENST00000343882, 
ENST00000406360, ENST00000540898, 
Fusion gene scores* DoF score21 X 18 X 10=378010 X 7 X 6=420
# samples 2510
** MAII scorelog2(25/3780*10)=-3.91838623444635
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/420*10)=-2.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: HIVEP3 [Title/Abstract] AND FOXO3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointHIVEP3(42094419)-FOXO3(108984657), # 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
HgeneHIVEP3

GO:0045893

positive regulation of transcription, DNA-templated

15790681

TgeneFOXO3

GO:0000122

negative regulation of transcription by RNA polymerase II

20371612

TgeneFOXO3

GO:0006417

regulation of translation

21329882

TgeneFOXO3

GO:0043065

positive regulation of apoptotic process

20371612

TgeneFOXO3

GO:0045648

positive regulation of erythrocyte differentiation

14734530

TgeneFOXO3

GO:0045893

positive regulation of transcription, DNA-templated

10102273|15084260

TgeneFOXO3

GO:0045944

positive regulation of transcription by RNA polymerase II

10102273|14734530


check buttonFusion gene breakpoints across HIVEP3 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonFusion gene breakpoints across FOXO3 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4OVTCGA-25-1319HIVEP3chr1

42094419

-FOXO3chr6

108984657

+


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Fusion Gene ORF analysis for HIVEP3-FOXO3

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5UTR-3CDSENST00000372583ENST00000343882HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-3CDSENST00000372583ENST00000406360HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-5UTRENST00000372583ENST00000540898HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-3CDSENST00000372584ENST00000343882HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-3CDSENST00000372584ENST00000406360HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-5UTRENST00000372584ENST00000540898HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-3CDSENST00000247584ENST00000343882HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-3CDSENST00000247584ENST00000406360HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-5UTRENST00000247584ENST00000540898HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-3CDSENST00000429157ENST00000343882HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-3CDSENST00000429157ENST00000406360HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
5UTR-5UTRENST00000429157ENST00000540898HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
intron-3CDSENST00000460604ENST00000343882HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
intron-3CDSENST00000460604ENST00000406360HIVEP3chr1

42094419

-FOXO3chr6

108984657

+
intron-5UTRENST00000460604ENST00000540898HIVEP3chr1

42094419

-FOXO3chr6

108984657

+

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)

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

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Fusion Genomic Features for HIVEP3-FOXO3


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)
HIVEP3chr142094419-FOXO3chr6108984657+0.0001105750.9998894
HIVEP3chr142094419-FOXO3chr6108984657+0.0001105750.9998894

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for HIVEP3-FOXO3


check button Go to

FGviewer for the breakpoints of :-:

.
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
HIVEP3

Q5T1R4

FOXO3

O43524

FUNCTION: Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Binds also to the kappa-B motif of gene such as S100A4, involved in cell progression and differentiation. Kappa-B motif is a gene regulatory element found in promoters and enhancers of genes involved in immunity, inflammation, and growth and that responds to viral antigens, mitogens, and cytokines. Involvement of HIVEP3 in cell growth is strengthened by the fact that its down-regulation promotes cell cycle progression with ultimate formation of multinucleated giant cells. Strongly inhibits TNF-alpha-induced NF-kappa-B activation; Interferes with nuclear factor NF-kappa-B by several mechanisms: as transcription factor, by competing for Kappa-B motif and by repressing transcription in the nucleus; through a non transcriptional process, by inhibiting nuclear translocation of RELA by association with TRAF2, an adapter molecule in the tumor necrosis factor signaling, which blocks the formation of IKK complex. Interaction with TRAF proteins inhibits both NF-Kappa-B-mediated and c-Jun N-terminal kinase/JNK-mediated responses that include apoptosis and proinflammatory cytokine gene expression. Positively regulates the expression of IL2 in T-cell. Essential regulator of adult bone formation. {ECO:0000269|PubMed:11161801}.FUNCTION: Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:10102273, PubMed:16751106, PubMed:21329882). Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins (By similarity). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (PubMed:10102273, PubMed:16751106). Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (PubMed:21329882). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription (PubMed:23283301). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). {ECO:0000250|UniProtKB:Q9WVH4, ECO:0000269|PubMed:10102273, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:23283301}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page


* Minus value of BPloci means that the break pointn is located before the CDS.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for HIVEP3-FOXO3


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for HIVEP3-FOXO3


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for HIVEP3-FOXO3


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for HIVEP3-FOXO3


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneHIVEP3C1535926Neurodevelopmental Disorders1CTD_human
TgeneFOXO3C0002152Alloxan Diabetes2CTD_human
TgeneFOXO3C0011853Diabetes Mellitus, Experimental2CTD_human
TgeneFOXO3C0038433Streptozotocin Diabetes2CTD_human
TgeneFOXO3C0007131Non-Small Cell Lung Carcinoma1CTD_human
TgeneFOXO3C0010606Adenoid Cystic Carcinoma1CTD_human
TgeneFOXO3C0014072Experimental Autoimmune Encephalomyelitis1CTD_human
TgeneFOXO3C0024117Chronic Obstructive Airway Disease1CTD_human
TgeneFOXO3C0028754Obesity1CTD_human
TgeneFOXO3C0152013Adenocarcinoma of lung (disorder)1CTD_human
TgeneFOXO3C1527303Chronic Airflow Obstruction1CTD_human