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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:ISG15-IFITM1 (FusionGDB2 ID:40301)

Fusion Gene Summary for ISG15-IFITM1

check button Fusion gene summary
Fusion gene informationFusion gene name: ISG15-IFITM1
Fusion gene ID: 40301
HgeneTgene
Gene symbol

ISG15

IFITM1

Gene ID

9636

8519

Gene nameISG15 ubiquitin like modifierinterferon induced transmembrane protein 1
SynonymsG1P2|IFI15|IMD38|IP17|UCRP|hUCRP9-27|CD225|DSPA2a|IFI17|LEU13
Cytomap

1p36.33

11p15.5

Type of geneprotein-codingprotein-coding
Descriptionubiquitin-like protein ISG15interferon, alpha-inducible protein (clone IFI-15K)interferon-induced 17-kDa/15-kDa proteininterferon-stimulated protein, 15 kDaubiquitin cross-reactive proteininterferon-induced transmembrane protein 1dispanin subfamily A member 2ainterferon-induced protein 17interferon-inducible protein 9-27leu-13 antigen
Modification date2020031320200313
UniProtAcc

P05161

A6NMD0

Ensembl transtripts involved in fusion geneENST00000379389, ENST00000525554, 
ENST00000408968, ENST00000528780, 
ENST00000328221, 
Fusion gene scores* DoF score2 X 1 X 1=27 X 8 X 5=280
# samples 18
** MAII scorelog2(1/2*10)=2.32192809488736log2(8/280*10)=-1.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: ISG15 [Title/Abstract] AND IFITM1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointISG15(949543)-IFITM1(314961), # samples:1
Anticipated loss of major functional domain due to fusion event.ISG15-IFITM1 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted 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
HgeneISG15

GO:0007229

integrin-mediated signaling pathway

29100055

HgeneISG15

GO:0031397

negative regulation of protein ubiquitination

18305167

HgeneISG15

GO:0032020

ISG15-protein conjugation

16122702|21543490

HgeneISG15

GO:0034340

response to type I interferon

22859821

HgeneISG15

GO:0072608

interleukin-10 secretion

29100055

HgeneISG15

GO:0072643

interferon-gamma secretion

29100055

TgeneIFITM1

GO:0009615

response to virus

21253575|22479637

TgeneIFITM1

GO:0034341

response to interferon-gamma

21253575

TgeneIFITM1

GO:0035455

response to interferon-alpha

22479637

TgeneIFITM1

GO:0035456

response to interferon-beta

21253575

TgeneIFITM1

GO:0045071

negative regulation of viral genome replication

21253575

TgeneIFITM1

GO:0046597

negative regulation of viral entry into host cell

21253575|23358889


check buttonFusion gene breakpoints across ISG15 (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 IFITM1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

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
ChimerDB4UCECTCGA-EY-A1GR-01AISG15chr1

949543

+IFITM1chr11

314961

+


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Fusion Gene ORF analysis for ISG15-IFITM1

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-intronENST00000379389ENST00000525554ISG15chr1

949543

+IFITM1chr11

314961

+
Frame-shiftENST00000379389ENST00000408968ISG15chr1

949543

+IFITM1chr11

314961

+
Frame-shiftENST00000379389ENST00000528780ISG15chr1

949543

+IFITM1chr11

314961

+
In-frameENST00000379389ENST00000328221ISG15chr1

949543

+IFITM1chr11

314961

+

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)
ENST00000379389ISG15chr1949543+ENST00000328221IFITM1chr11314961+81053122468148

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
ENST00000379389ENST00000328221ISG15chr1949543+IFITM1chr11314961+0.198417860.80158216

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Fusion Genomic Features for ISG15-IFITM1


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)

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.
genomic feature

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 ISG15-IFITM1


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/chr1:949543/chr11:314961)
- 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
ISG15

P05161

IFITM1

A6NMD0

FUNCTION: Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Can also isgylate: EIF2AK2/PKR which results in its activation, DDX58/RIG-I which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade thereby inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL (PubMed:29100055). {ECO:0000269|PubMed:1373138, ECO:0000269|PubMed:16009940, ECO:0000269|PubMed:16112642, ECO:0000269|PubMed:16428300, ECO:0000269|PubMed:16434471, ECO:0000269|PubMed:16872604, ECO:0000269|PubMed:18305167, ECO:0000269|PubMed:19270716, ECO:0000269|PubMed:19357168, ECO:0000269|PubMed:2005397, ECO:0000269|PubMed:20133869, ECO:0000269|PubMed:20308324, ECO:0000269|PubMed:20639253, ECO:0000269|PubMed:21543490, ECO:0000269|PubMed:22693631, ECO:0000269|PubMed:22859821, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:29100055, ECO:0000269|PubMed:7526157, ECO:0000269|PubMed:8550581}.

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
TgeneIFITM1chr1:949543chr11:314961ENST000003282210337_570126.0IntramembraneHelical
TgeneIFITM1chr1:949543chr11:314961ENST000004089680237_570126.0IntramembraneHelical
TgeneIFITM1chr1:949543chr11:314961ENST000005287800337_570126.0IntramembraneHelical
TgeneIFITM1chr1:949543chr11:314961ENST0000032822103108_1250126.0Topological domainExtracellular
TgeneIFITM1chr1:949543chr11:314961ENST00000328221031_360126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST000003282210358_860126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST0000040896802108_1250126.0Topological domainExtracellular
TgeneIFITM1chr1:949543chr11:314961ENST00000408968021_360126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST000004089680258_860126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST0000052878003108_1250126.0Topological domainExtracellular
TgeneIFITM1chr1:949543chr11:314961ENST00000528780031_360126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST000005287800358_860126.0Topological domainCytoplasmic
TgeneIFITM1chr1:949543chr11:314961ENST000003282210387_1070126.0TransmembraneHelical
TgeneIFITM1chr1:949543chr11:314961ENST000004089680287_1070126.0TransmembraneHelical
TgeneIFITM1chr1:949543chr11:314961ENST000005287800387_1070126.0TransmembraneHelical

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneISG15chr1:949543chr11:314961ENST00000379389+122_780166.0DomainUbiquitin-like 1
HgeneISG15chr1:949543chr11:314961ENST00000379389+1279_1570166.0DomainUbiquitin-like 2
HgeneISG15chr1:949543chr11:314961ENST00000379389+12152_1570166.0MotifNote=LRLRGG
HgeneISG15chr1:949543chr11:314961ENST00000379389+12153_1570166.0RegionInvolved in the ligation of specific target proteins


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Fusion Gene Sequence for ISG15-IFITM1


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.
>40301_40301_1_ISG15-IFITM1_ISG15_chr1_949543_ENST00000379389_IFITM1_chr11_314961_ENST00000328221_length(transcript)=810nt_BP=531nt
CGCAGGCTCGGCGGCACGCCCCCTGACGTGTGTGCCTCAGGCTTATAATAGGGCCGGTGCTGCCTGCCGAAGCCGGCGGCTGAGAGGCAG
CGAACTCATCTTTGCCAGTACAGGAGCTTGTGCCGTGGCCCACAGCCCACAGCCCACAGCCATGAGCCAGGGCCTGGGCCCCGGCAGCAC
GGTCCTGCTGGTGGTGGACAAATGCGACGAACCTCTGAGCATCCTGGTGAGGAATAACAAGGGCCGCAGCAGCACCTACGAGGTACGGCT
GACGCAGACCGTGGCCCACCTGAAGCAGCAAGTGAGCGGGCTGGAGGGTGTGCAGGACGACCTGTTCTGGCTGACCTTCGAGGGGAAGCC
CCTGGAGGACCAGCTCCCGCTGGGGGAGTACGGCCTCAAGCCCCTGAGCACCGTGTTCATGAATCTGCGCCTGCGGGGAGGCGGCACAGA
GCCTGGCGGGCGGAGCTAAGGGCCTCCACCAGCATCCGAGCAGGATCAAGGGCCGGAAATAAAGGCTGTTGTAAAGAGAAAAGGCCTATG
CCTCCACCGCCAAGTGCCTGAACATCTGGGCCCTGATTCTGGGCATCCTCATGACCATTGGATTCATCCTGTTACTGGTATTCGGCTCTG
TGACAGTCTACCATATTATGTTACAGATAATACAGGAAAAACGGGGTTACTAGTAGCCGCCCATAGCCTGCAACCTTTGCACTCCACTGT
GCAATGCTGGCCCTGCACGCTGGGGCTGTTGCCCCTGCCCCCTTGGTCCTGCCCCTAGATACAGCAGTTTATACCCACACACCTGTCTAC

>40301_40301_1_ISG15-IFITM1_ISG15_chr1_949543_ENST00000379389_IFITM1_chr11_314961_ENST00000328221_length(amino acids)=148AA_BP=
MTCVPQAYNRAGAACRSRRLRGSELIFASTGACAVAHSPQPTAMSQGLGPGSTVLLVVDKCDEPLSILVRNNKGRSSTYEVRLTQTVAHL

--------------------------------------------------------------

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Fusion Gene PPI Analysis for ISG15-IFITM1


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
TgeneIFITM1chr1:949543chr11:314961ENST000003282210384_1250126.0CAV1
TgeneIFITM1chr1:949543chr11:314961ENST000004089680284_1250126.0CAV1
TgeneIFITM1chr1:949543chr11:314961ENST000005287800384_1250126.0CAV1


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 ISG15-IFITM1


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 ISG15-IFITM1


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