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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:FOXO3-LETMD1 (FusionGDB2 ID:31178)

Fusion Gene Summary for FOXO3-LETMD1

check button Fusion gene summary
Fusion gene informationFusion gene name: FOXO3-LETMD1
Fusion gene ID: 31178
HgeneTgene
Gene symbol

FOXO3

LETMD1

Gene ID

2309

25875

Gene nameforkhead box O3LETM1 domain containing 1
SynonymsAF6q21|FKHRL1|FKHRL1P2|FOXO2|FOXO3A1110019O13Rik|HCCR|HCCR-1|HCCR-2|HCCR1|HCCR2|HCRR-2|SLC55A3
Cytomap

6q21

12q13.12

Type of geneprotein-codingprotein-coding
Descriptionforkhead box protein O3forkhead box O3Aforkhead homolog (rhabdomyosarcoma) like 1forkhead in rhabdomyosarcoma-like 1forkhead, Drosophila, homolog of, in rhabdomyosarcoma-like 1LETM1 domain-containing protein 1cervical cancer 1 proto-oncogene protein p40cervical cancer proto-oncogene 2 proteinepididymis secretory sperm binding proteinhuman cervical cancer oncogeneregulator of TP53
Modification date2020032920200322
UniProtAcc

O43524

Q6P1Q0

Ensembl transtripts involved in fusion geneENST00000343882, ENST00000406360, 
ENST00000540898, 
ENST00000548516, 
ENST00000262055, ENST00000380123, 
ENST00000418425, ENST00000547008, 
ENST00000550929, ENST00000552739, 
Fusion gene scores* DoF score9 X 5 X 7=3155 X 3 X 4=60
# samples 125
** MAII scorelog2(12/315*10)=-1.39231742277876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/60*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: FOXO3 [Title/Abstract] AND LETMD1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointFOXO3(108883032)-LETMD1(51442817), # 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
HgeneFOXO3

GO:0000122

negative regulation of transcription by RNA polymerase II

20371612

HgeneFOXO3

GO:0006417

regulation of translation

21329882

HgeneFOXO3

GO:0043065

positive regulation of apoptotic process

20371612

HgeneFOXO3

GO:0045648

positive regulation of erythrocyte differentiation

14734530

HgeneFOXO3

GO:0045893

positive regulation of transcription, DNA-templated

10102273|15084260

HgeneFOXO3

GO:0045944

positive regulation of transcription by RNA polymerase II

10102273|14734530


check buttonFusion gene breakpoints across FOXO3 (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 LETMD1 (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
ChimerDB4GBMTCGA-06-2561-01AFOXO3chr6

108883032

+LETMD1chr12

51442817

+


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Fusion Gene ORF analysis for FOXO3-LETMD1

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
5CDS-3UTRENST00000343882ENST00000548516FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-3UTRENST00000406360ENST00000548516FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-5UTRENST00000343882ENST00000262055FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-5UTRENST00000343882ENST00000380123FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-5UTRENST00000343882ENST00000418425FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-5UTRENST00000343882ENST00000547008FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-5UTRENST00000343882ENST00000550929FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-5UTRENST00000406360ENST00000262055FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-5UTRENST00000406360ENST00000380123FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-5UTRENST00000406360ENST00000418425FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-5UTRENST00000406360ENST00000547008FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-5UTRENST00000406360ENST00000550929FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-intronENST00000343882ENST00000552739FOXO3chr6

108883032

+LETMD1chr12

51442817

+
5CDS-intronENST00000406360ENST00000552739FOXO3chr6

108883032

+LETMD1chr12

51442817

+
intron-3UTRENST00000540898ENST00000548516FOXO3chr6

108883032

+LETMD1chr12

51442817

+
intron-5UTRENST00000540898ENST00000262055FOXO3chr6

108883032

+LETMD1chr12

51442817

+
intron-5UTRENST00000540898ENST00000380123FOXO3chr6

108883032

+LETMD1chr12

51442817

+
intron-5UTRENST00000540898ENST00000418425FOXO3chr6

108883032

+LETMD1chr12

51442817

+
intron-5UTRENST00000540898ENST00000547008FOXO3chr6

108883032

+LETMD1chr12

51442817

+
intron-5UTRENST00000540898ENST00000550929FOXO3chr6

108883032

+LETMD1chr12

51442817

+
intron-intronENST00000540898ENST00000552739FOXO3chr6

108883032

+LETMD1chr12

51442817

+

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 FOXO3-LETMD1


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)
FOXO3chr6108883032+LETMD1chr1251442816+4.85E-050.9999515
FOXO3chr6108883032+LETMD1chr1251442816+4.85E-050.9999515

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.
genomic feature of top 1%

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Fusion Protein Features for FOXO3-LETMD1


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/:108883032/:51442817)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
FOXO3

O43524

LETMD1

Q6P1Q0

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}.FUNCTION: Involved in tumorigenesis and may function as a negative regulator of the p53/TP53. {ECO:0000269|PubMed:12879013}.

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 FOXO3-LETMD1


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 FOXO3-LETMD1


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 FOXO3-LETMD1


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 FOXO3-LETMD1


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource