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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:IGF1R-TMSB4X (FusionGDB2 ID:HG3480TG7114)

Fusion Gene Summary for IGF1R-TMSB4X

check button Fusion gene summary
Fusion gene informationFusion gene name: IGF1R-TMSB4X
Fusion gene ID: hg3480tg7114
HgeneTgene
Gene symbol

IGF1R

TMSB4X

Gene ID

3480

7114

Gene nameinsulin like growth factor 1 receptorthymosin beta 4 X-linked
SynonymsCD221|IGFIR|IGFR|JTK13FX|PTMB4|TB4X|TMSB4
Cytomap('IGF1R')('TMSB4X')

15q26.3

Xp22.2

Type of geneprotein-codingprotein-coding
Descriptioninsulin-like growth factor 1 receptorIGF-I receptorsoluble IGF1R variant 1soluble IGF1R variant 2thymosin beta-4prothymosin beta-4t beta-4thymosin, beta 4, X chromosome
Modification date2020032920200313
UniProtAcc

P08069

.
Ensembl transtripts involved in fusion geneENST00000268035, ENST00000558762, 
ENST00000560432, 
Fusion gene scores* DoF score24 X 15 X 6=216010 X 7 X 4=280
# samples 2510
** MAII scorelog2(25/2160*10)=-3.11103131238874
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(10/280*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: IGF1R [Title/Abstract] AND TMSB4X [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointIGF1R(99223162)-TMSB4X(12995342), # 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
HgeneIGF1R

GO:0043066

negative regulation of apoptotic process

12556535

HgeneIGF1R

GO:0046328

regulation of JNK cascade

12556535

HgeneIGF1R

GO:0046777

protein autophosphorylation

1846292|7679099|11162456

HgeneIGF1R

GO:0048009

insulin-like growth factor receptor signaling pathway

7679099

HgeneIGF1R

GO:0048015

phosphatidylinositol-mediated signaling

7692086

HgeneIGF1R

GO:0051389

inactivation of MAPKK activity

12556535

TgeneTMSB4X

GO:0042989

sequestering of actin monomers

1447300|1999398

TgeneTMSB4X

GO:0043536

positive regulation of blood vessel endothelial cell migration

21106936

TgeneTMSB4X

GO:1903026

negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding

21343177

TgeneTMSB4X

GO:1905273

positive regulation of proton-transporting ATP synthase activity, rotational mechanism

21106936

TgeneTMSB4X

GO:2000483

negative regulation of interleukin-8 secretion

21343177

TgeneTMSB4X

GO:2001028

positive regulation of endothelial cell chemotaxis

21106936

TgeneTMSB4X

GO:2001171

positive regulation of ATP biosynthetic process

21106936



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/ABF477802IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-


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Fusion Gene ORF analysis for IGF1R-TMSB4X

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
intron-intronENST00000268035ENST00000380633IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000268035ENST00000380635IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000268035ENST00000380636IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000268035ENST00000451311IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000558762ENST00000380633IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000558762ENST00000380635IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000558762ENST00000380636IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000558762ENST00000451311IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000560432ENST00000380633IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000560432ENST00000380635IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000560432ENST00000380636IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-
intron-intronENST00000560432ENST00000451311IGF1Rchr15

99223162

-TMSB4XchrX

12995342

-

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 IGF1R-TMSB4X


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)


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Fusion Protein Features for IGF1R-TMSB4X


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/:99223162/:12995342)
- 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
IGF1R

P08069

.
FUNCTION: Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.; FUNCTION: When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.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}.

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 IGF1R-TMSB4X


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 IGF1R-TMSB4X


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 IGF1R-TMSB4X


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
HgeneIGF1RP08069DB00046Insulin lisproBiotechApproved
HgeneIGF1RP08069DB00047Insulin glargineBiotechApproved
HgeneIGF1RP08069DB00071Insulin porkBiotechApproved
HgeneIGF1RP08069DB01306Insulin aspartBiotechApproved
HgeneIGF1RP08069DB01307Insulin detemirBiotechApproved
HgeneIGF1RP08069DB01309Insulin glulisineBiotechApproved
HgeneIGF1RP08069DB09564Insulin degludecBiotechApproved
HgeneIGF1RP08069DB14751Mecasermin rinfabateAgonistBiotechApproved
HgeneIGF1RP08069DB00030Insulin humanBiotechApproved|Investigational
HgeneIGF1RP08069DB01277MecaserminAgonistBiotechApproved|Investigational
HgeneIGF1RP08069DB06343TeprotumumabInhibitorBiotechApproved|Investigational
HgeneIGF1RP08069DB12267BrigatinibInhibitorSmall moleculeApproved|Investigational
HgeneIGF1RP08069DB09098SomatremBiotechApproved|Investigational|Withdrawn

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Related Diseases for IGF1R-TMSB4X


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneIGF1RC1849157Resistance to Insulin-Like Growth Factor I5CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
HgeneIGF1RC0004238Atrial Fibrillation2CTD_human
HgeneIGF1RC0024115Lung diseases2CTD_human
HgeneIGF1RC0235480Paroxysmal atrial fibrillation2CTD_human
HgeneIGF1RC0235833Congenital diaphragmatic hernia2CTD_human
HgeneIGF1RC0265699Congenital hernia of foramen of Morgagni2CTD_human
HgeneIGF1RC0265700Congenital hernia of foramen of Bochdalek2CTD_human
HgeneIGF1RC2239176Liver carcinoma2CTD_human
HgeneIGF1RC2585653Persistent atrial fibrillation2CTD_human
HgeneIGF1RC3468561familial atrial fibrillation2CTD_human
HgeneIGF1RC0002395Alzheimer's Disease1CTD_human
HgeneIGF1RC0006142Malignant neoplasm of breast1CTD_human
HgeneIGF1RC0007114Malignant neoplasm of skin1CTD_human
HgeneIGF1RC0007621Neoplastic Cell Transformation1CTD_human
HgeneIGF1RC0011265Presenile dementia1CTD_human
HgeneIGF1RC0014170Endometrial Neoplasms1CTD_human
HgeneIGF1RC0015934Fetal Growth Retardation1CTD_human
HgeneIGF1RC0018273Growth Disorders1CTD_human
HgeneIGF1RC0030567Parkinson Disease1CTD_human
HgeneIGF1RC0035229Respiratory Insufficiency1CTD_human
HgeneIGF1RC0037286Skin Neoplasms1CTD_human
HgeneIGF1RC0087031Juvenile-Onset Still Disease1CTD_human
HgeneIGF1RC0206686Adrenocortical carcinoma1CTD_human
HgeneIGF1RC0235063Respiratory Depression1CTD_human
HgeneIGF1RC0276496Familial Alzheimer Disease (FAD)1CTD_human
HgeneIGF1RC0424605Developmental delay (disorder)1GENOMICS_ENGLAND
HgeneIGF1RC0476089Endometrial Carcinoma1CTD_human
HgeneIGF1RC0494463Alzheimer Disease, Late Onset1CTD_human
HgeneIGF1RC0546126Acute Confusional Senile Dementia1CTD_human
HgeneIGF1RC0557874Global developmental delay1GENOMICS_ENGLAND
HgeneIGF1RC0678222Breast Carcinoma1CTD_human
HgeneIGF1RC0750900Alzheimer's Disease, Focal Onset1CTD_human
HgeneIGF1RC0750901Alzheimer Disease, Early Onset1CTD_human
HgeneIGF1RC0752347Lewy Body Disease1CTD_human
HgeneIGF1RC1145670Respiratory Failure1CTD_human
HgeneIGF1RC1257931Mammary Neoplasms, Human1CTD_human
HgeneIGF1RC1458155Mammary Neoplasms1CTD_human
HgeneIGF1RC3495559Juvenile arthritis1CTD_human
HgeneIGF1RC3714758Juvenile psoriatic arthritis1CTD_human
HgeneIGF1RC4552091Polyarthritis, Juvenile, Rheumatoid Factor Negative1CTD_human
HgeneIGF1RC4704862Polyarthritis, Juvenile, Rheumatoid Factor Positive1CTD_human
HgeneIGF1RC4704874Mammary Carcinoma, Human1CTD_human
HgeneIGF1RC4721453Peripheral Nervous System Diseases1CTD_human
TgeneC0033578Prostatic Neoplasms1CTD_human
TgeneC0376358Malignant neoplasm of prostate1CTD_human
TgeneC1862939AMYOTROPHIC LATERAL SCLEROSIS 11CTD_human
TgeneC1862941Amyotrophic Lateral Sclerosis, Sporadic1CTD_human
TgeneC4551993Amyotrophic Lateral Sclerosis, Familial1CTD_human