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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:TPM4-IL6ST (FusionGDB2 ID:93405)

Fusion Gene Summary for TPM4-IL6ST

check button Fusion gene summary
Fusion gene informationFusion gene name: TPM4-IL6ST
Fusion gene ID: 93405
HgeneTgene
Gene symbol

TPM4

IL6ST

Gene ID

7171

3572

Gene nametropomyosin 4interleukin 6 signal transducer
SynonymsHEL-S-108CD130|CDW130|GP130|HIES4|IL-6RB|sGP130
Cytomap

19p13.12-p13.11

5q11.2

Type of geneprotein-codingprotein-coding
Descriptiontropomyosin alpha-4 chainTM30p1epididymis secretory protein Li 108interleukin-6 receptor subunit betaCD130 antigenIL-6 receptor subunit betaIL-6R subunit betagp130 of the rheumatoid arthritis antigenic peptide-bearing soluble formgp130, oncostatin M receptorinterleukin receptor beta chainmembrane glycoprotein 130
Modification date2020032020200327
UniProtAcc.

P40189

Ensembl transtripts involved in fusion geneENST00000300933, ENST00000344824, 
ENST00000538887, ENST00000591645, 
ENST00000336909, ENST00000381286, 
ENST00000381287, ENST00000381293, 
ENST00000381294, ENST00000381298, 
ENST00000396816, ENST00000502326, 
ENST00000522633, ENST00000536319, 
ENST00000577363, 
Fusion gene scores* DoF score22 X 19 X 9=37627 X 8 X 3=168
# samples 258
** MAII scorelog2(25/3762*10)=-3.91149984886111
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(8/168*10)=-1.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: TPM4 [Title/Abstract] AND IL6ST [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointTPM4(16213646)-IL6ST(55240721), # 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
TgeneIL6ST

GO:0008284

positive regulation of cell proliferation

2261637

TgeneIL6ST

GO:0019221

cytokine-mediated signaling pathway

2261637

TgeneIL6ST

GO:0034097

response to cytokine

2261637|8999038

TgeneIL6ST

GO:0048861

leukemia inhibitory factor signaling pathway

8999038|12643274

TgeneIL6ST

GO:0070120

ciliary neurotrophic factor-mediated signaling pathway

12643274


check buttonFusion gene breakpoints across TPM4 (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 IL6ST (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
ChiTaRS5.0N/ABI858389TPM4chr19

16213646

+IL6STchr5

55240721

+


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Fusion Gene ORF analysis for TPM4-IL6ST

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
3UTR-intronENST00000300933ENST00000336909TPM4chr19

16213646

+IL6STchr5

55240721

+
3UTR-intronENST00000300933ENST00000381286TPM4chr19

16213646

+IL6STchr5

55240721

+
3UTR-intronENST00000300933ENST00000381287TPM4chr19

16213646

+IL6STchr5

55240721

+
3UTR-intronENST00000300933ENST00000381293TPM4chr19

16213646

+IL6STchr5

55240721

+
3UTR-intronENST00000300933ENST00000381294TPM4chr19

16213646

+IL6STchr5

55240721

+
3UTR-intronENST00000300933ENST00000381298TPM4chr19

16213646

+IL6STchr5

55240721

+
3UTR-intronENST00000300933ENST00000396816TPM4chr19

16213646

+IL6STchr5

55240721

+
3UTR-intronENST00000300933ENST00000502326TPM4chr19

16213646

+IL6STchr5

55240721

+
3UTR-intronENST00000300933ENST00000522633TPM4chr19

16213646

+IL6STchr5

55240721

+
3UTR-intronENST00000300933ENST00000536319TPM4chr19

16213646

+IL6STchr5

55240721

+
3UTR-intronENST00000300933ENST00000577363TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000336909TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000381286TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000381287TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000381293TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000381294TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000381298TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000396816TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000502326TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000522633TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000536319TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000344824ENST00000577363TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000336909TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000381286TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000381287TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000381293TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000381294TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000381298TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000396816TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000502326TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000522633TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000536319TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000538887ENST00000577363TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000336909TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000381286TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000381287TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000381293TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000381294TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000381298TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000396816TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000502326TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000522633TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000536319TPM4chr19

16213646

+IL6STchr5

55240721

+
intron-intronENST00000591645ENST00000577363TPM4chr19

16213646

+IL6STchr5

55240721

+

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 TPM4-IL6ST


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.

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 TPM4-IL6ST


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/:16213646/:55240721)
- 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
.IL6ST

P40189

FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.FUNCTION: Signal-transducing molecule (PubMed:2261637). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activate the intracellular JAK-MAPK and JAK-STAT3 signaling pathways (PubMed:2261637, PubMed:19915009, PubMed:23294003). That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3 (PubMed:19915009, PubMed:23294003, PubMed:25731159). In parallel, the IL6 signaling pathway induces the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop (By similarity). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (By similarity). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (By similarity). Required for expression of TRPA1 in nociceptive neurons (By similarity). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (By similarity). Required for normal trabecular bone mass and cortical bone composition (By similarity). {ECO:0000250|UniProtKB:Q00560, ECO:0000269|PubMed:19915009, ECO:0000269|PubMed:2261637, ECO:0000269|PubMed:23294003, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:28747427, ECO:0000269|PubMed:30309848}.; FUNCTION: [Isoform 2]: Binds to the soluble IL6:sIL6R complex (hyper-IL6), thereby blocking IL6 trans-signaling. Inhibits sIL6R-dependent acute phase response (PubMed:11121117, PubMed:21990364, PubMed:30279168). Also blocks IL11 cluster signaling through IL11R (PubMed:30279168). {ECO:0000269|PubMed:11121117, ECO:0000269|PubMed:21990364, ECO:0000269|PubMed:30279168}.

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 TPM4-IL6ST


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 TPM4-IL6ST


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 TPM4-IL6ST


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 TPM4-IL6ST


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