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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:FOXO1-PDGFRB

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: FOXO1-PDGFRB
	FusionPDB ID: 31166
	FusionGDB2.0 ID: 31166
		Hgene	Tgene
	Gene symbol	FOXO1	PDGFRB
	Gene ID	2308	5159
	Gene name	forkhead box O1	platelet derived growth factor receptor beta
	Synonyms	FKH1\|FKHR\|FOXO1A	CD140B\|IBGC4\|IMF1\|JTK12\|KOGS\|PDGFR\|PDGFR-1\|PDGFR1\|PENTT
	Cytomap	13q14.11	5q32
	Type of gene	protein-coding	protein-coding
	Description	forkhead box protein O1forkhead box protein O1Aforkhead, Drosophila, homolog of, in rhabdomyosarcoma	platelet-derived growth factor receptor betaActivated tyrosine kinase PDGFRBCD140 antigen-like family member BNDEL1-PDGFRBPDGF-R-betaPDGFR-betabeta-type platelet-derived growth factor receptorplatelet-derived growth factor receptor 1platelet-deriv
	Modification date	20200322	20200329
	UniProtAcc	Q12778	P09619
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000379561, ENST00000473775,	ENST00000523456, ENST00000261799,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	13 X 12 X 9=1404	28 X 26 X 6=4368
	# samples	16	15
	** MAII score	log2(16/1404*10)=-3.1333991254172 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(15/4368*10)=-4.86393845042397 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: FOXO1 [Title/Abstract] AND PDGFRB [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	FOXO1(41239720)-PDGFRB(149499686), # samples:2
Anticipated loss of major functional domain due to fusion event.	FOXO1-PDGFRB seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. FOXO1-PDGFRB seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. FOXO1-PDGFRB seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. FOXO1-PDGFRB seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.

* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	FOXO1	GO:0009267	cellular response to starvation	20543840
Hgene	FOXO1	GO:0032873	negative regulation of stress-activated MAPK cascade	19696738
Hgene	FOXO1	GO:0043066	negative regulation of apoptotic process	10871843
Hgene	FOXO1	GO:0045893	positive regulation of transcription, DNA-templated	7862145\|10871843\|12228231
Hgene	FOXO1	GO:0045944	positive regulation of transcription by RNA polymerase II	10871843\|12228231
Hgene	FOXO1	GO:0071455	cellular response to hyperoxia	20543840
Tgene	PDGFRB	GO:0007165	signal transduction	10821867
Tgene	PDGFRB	GO:0010863	positive regulation of phospholipase C activity	1653029
Tgene	PDGFRB	GO:0018108	peptidyl-tyrosine phosphorylation	1653029\|2536956\|2850496
Tgene	PDGFRB	GO:0030335	positive regulation of cell migration	17470632
Tgene	PDGFRB	GO:0032516	positive regulation of phosphoprotein phosphatase activity	7691811
Tgene	PDGFRB	GO:0038091	positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	17470632
Tgene	PDGFRB	GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity	1314164
Tgene	PDGFRB	GO:0046777	protein autophosphorylation	1314164\|2536956\|2850496
Tgene	PDGFRB	GO:0048008	platelet-derived growth factor receptor signaling pathway	1314164\|2536956
Tgene	PDGFRB	GO:0060326	cell chemotaxis	2554309\|17991872

Fusion gene breakpoints across FOXO1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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

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Fusion Gene Sample Information

Fusion gene information from FusionGDB2.0.

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.

Source	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	KICH	TCGA-KM-8443-01A	FOXO1	chr13	41239720	-	PDGFRB	chr5	149499686	-

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Fusion ORF Analysis

Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.

Henst

Tenst

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

Seq length
(transcript)

BP loci
(transcript)

Predicted start
(transcript)

Predicted stop
(transcript)

Seq length
(amino acids)

ENST00000379561

FOXO1

chr13

41239720

ENST00000261799

PDGFRB

chr5

149499686

3676

1015

1749

568

DeepORF 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.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	No-coding score	Coding score
ENST00000379561	ENST00000261799	FOXO1	chr13	41239720	-	PDGFRB	chr5	149499686	-	0.015304945	0.984695

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Fusion Amino Acid Sequences

For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>31166_31166_1_FOXO1-PDGFRB_FOXO1_chr13_41239720_ENST00000379561_PDGFRB_chr5_149499686_ENST00000261799_length(amino acids)=568AA_BP=324
MGRASGPRRPSVLPSAALSAGARRRLCPGPAALAGRPVRAADPEEPRCGWPREVKFWARASTPPRLPPSFRPLAAPASFPQISDRPFAPP
PRPPPVLRSPPLGSPAAGGGAGVTMAEAPQVVEIDPDFEPLPRPRSCTWPLPRPEFSQSNSATSSPAPSGSAAANPDAAAGLPSASAAAV
SADFMSNLSLLEESEDFPQAPGSVAAAVAAAAAAAATGGLCGDFQGPEAGCLHPAPPQPPPPGPLSQHPPVPPAAAGPLAGQPRKSSSSR
RNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKTFLPLKWMAPESIFNSLYTTLSDVWSFGILLWEIFT
LGGTPYPELPMNEQFYNAIKRGYRMAQPAHASDEIYEIMQKCWEEKFEIRPPFSQLVLLLERLLGEGYKKKYQQVDEEFLRSDHPAILRS
QARLPGFHGLRSPLDTSSVLYTAVQPNEGDNDYIIPLPDPKPEVADEGPLEGSPSLASSTLNEVNTSSTISCDSPLEPQDEPEPEPQLEL

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

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Fusion Protein Functional Features

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr13:41239720/chr5:149499686)
- 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.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
FOXO1 Q12778	PDGFRB P09619
FUNCTION: Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:10358076, PubMed:12228231, PubMed:15220471, PubMed:15890677, PubMed:18356527, PubMed:19221179, PubMed:20543840, PubMed:21245099). Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3' (PubMed:10358076). Activity suppressed by insulin (PubMed:10358076). Main regulator of redox balance and osteoblast numbers and controls bone mass (By similarity). Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (By similarity). 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). Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity (By similarity). Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP (By similarity). In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC1 and PCK1 (By similarity). Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1 (PubMed:18356527, PubMed:19221179). Promotes neural cell death (PubMed:18356527). Mediates insulin action on adipose tissue (By similarity). Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake (By similarity). Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells (By similarity). Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner (PubMed:20543840). Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity). Regulates endothelial cell (EC) viability and apoptosis in a PPIA/CYPA-dependent manner via transcription of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). {ECO:0000250\|UniProtKB:A4L7N3, ECO:0000250\|UniProtKB:G3V7R4, ECO:0000250\|UniProtKB:Q9R1E0, ECO:0000269\|PubMed:10358076, ECO:0000269\|PubMed:12228231, ECO:0000269\|PubMed:15220471, ECO:0000269\|PubMed:15890677, ECO:0000269\|PubMed:18356527, ECO:0000269\|PubMed:19221179, ECO:0000269\|PubMed:20543840, ECO:0000269\|PubMed:21245099, ECO:0000269\|PubMed:31063815}.	FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269\|PubMed:11297552, ECO:0000269\|PubMed:11331881, ECO:0000269\|PubMed:1314164, ECO:0000269\|PubMed:1396585, ECO:0000269\|PubMed:1653029, ECO:0000269\|PubMed:1709159, ECO:0000269\|PubMed:1846866, ECO:0000269\|PubMed:20494825, ECO:0000269\|PubMed:20529858, ECO:0000269\|PubMed:21098708, ECO:0000269\|PubMed:21679854, ECO:0000269\|PubMed:21733313, ECO:0000269\|PubMed:2554309, ECO:0000269\|PubMed:26599395, ECO:0000269\|PubMed:2835772, ECO:0000269\|PubMed:2850496, ECO:0000269\|PubMed:7685273, ECO:0000269\|PubMed:7691811, ECO:0000269\|PubMed:7692233, ECO:0000269\|PubMed:8195171}.

Retention 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.

- Retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

FOXO1

chr13:41239720

chr5:149499686

ENST00000379561

120_130

210.0

1440.3333333333333

Compositional bias

Note=Poly-Pro

Hgene

FOXO1

chr13:41239720

chr5:149499686

ENST00000379561

152_155

210.0

1440.3333333333333

Compositional bias

Note=Poly-Ser

Hgene

FOXO1

chr13:41239720

chr5:149499686

ENST00000379561

91_102

210.0

1440.3333333333333

Compositional bias

Note=Poly-Ala

- Not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

FOXO1

chr13:41239720

chr5:149499686

ENST00000379561

159_235

210.0

1440.3333333333333

DNA binding

Fork-head

Hgene

FOXO1

chr13:41239720

chr5:149499686

ENST00000379561

211_218

210.0

1440.3333333333333

Region

Note=DNA-binding

Hgene

FOXO1

chr13:41239720

chr5:149499686

ENST00000379561

234_237

210.0

1440.3333333333333

Region

Note=DNA-binding

Tgene

PDGFRB

chr13:41239720

chr5:149499686

ENST00000261799

129_210

862.0

1107.0

Domain

Note=Ig-like C2-type 2

Tgene

PDGFRB

chr13:41239720

chr5:149499686

ENST00000261799

214_309

862.0

1107.0

Domain

Note=Ig-like C2-type 3

Tgene

PDGFRB

chr13:41239720

chr5:149499686

ENST00000261799

331_403

862.0

1107.0

Domain

Note=Ig-like C2-type 4

Tgene

PDGFRB

chr13:41239720

chr5:149499686

ENST00000261799

33_120

862.0

1107.0

Domain

Note=Ig-like C2-type 1

Tgene

PDGFRB

chr13:41239720

chr5:149499686

ENST00000261799

416_524

862.0

1107.0

Domain

Note=Ig-like C2-type 5

Tgene

PDGFRB

chr13:41239720

chr5:149499686

ENST00000261799

600_962

862.0

1107.0

Domain

Protein kinase

Tgene

PDGFRB

chr13:41239720

chr5:149499686

ENST00000261799

606_614

862.0

1107.0

Nucleotide binding

ATP

Tgene

PDGFRB

chr13:41239720

chr5:149499686

ENST00000261799

33_532

862.0

1107.0

Topological domain

Extracellular

Tgene

PDGFRB

chr13:41239720

chr5:149499686

ENST00000261799

554_1106

862.0

1107.0

Topological domain

Cytoplasmic

Tgene

PDGFRB

chr13:41239720

chr5:149499686

ENST00000261799

533_553

862.0

1107.0

Transmembrane

Helical

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Fusion Protein-Protein Interaction

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)

Gene

PPI interactors

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
FOXO1
PDGFRB

- Retained interactions in fusion protein (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost interactions due to fusion (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs to FOXO1-PDGFRB

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

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Related Diseases to FOXO1-PDGFRB

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner	Gene	Disease ID	Disease name	# pubmeds	Source
Hgene	FOXO1	C0020542	Pulmonary Hypertension	1	CTD_human
Hgene	FOXO1	C0022578	Keratoconus	1	CTD_human
Hgene	FOXO1	C0023467	Leukemia, Myelocytic, Acute	1	CTD_human
Hgene	FOXO1	C0026998	Acute Myeloid Leukemia, M1	1	CTD_human
Hgene	FOXO1	C0033578	Prostatic Neoplasms	1	CTD_human
Hgene	FOXO1	C0206655	Alveolar rhabdomyosarcoma	1	CTD_human;GENOMICS_ENGLAND;ORPHANET
Hgene	FOXO1	C0376358	Malignant neoplasm of prostate	1	CTD_human
Hgene	FOXO1	C1879321	Acute Myeloid Leukemia (AML-M2)	1	CTD_human
Tgene	PDGFRB	C3554321	BASAL GANGLIA CALCIFICATION, IDIOPATHIC, 4	6	CTD_human;GENOMICS_ENGLAND;UNIPROT
Tgene	PDGFRB	C0393590	Fahr's syndrome (disorder)	3	GENOMICS_ENGLAND;ORPHANET
Tgene	PDGFRB	C4225270	Kosaki overgrowth syndrome	3	CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Tgene	PDGFRB	C4551572	MYOFIBROMATOSIS, INFANTILE, 1	3	GENOMICS_ENGLAND;UNIPROT
Tgene	PDGFRB	C0013421	Dystonia	2	GENOMICS_ENGLAND
Tgene	PDGFRB	C0023480	Leukemia, Myelomonocytic, Chronic	2	ORPHANET
Tgene	PDGFRB	C0023893	Liver Cirrhosis, Experimental	2	CTD_human
Tgene	PDGFRB	C0036341	Schizophrenia	2	PSYGENET
Tgene	PDGFRB	C0432284	Infantile myofibromatosis	2	CTD_human;GENOMICS_ENGLAND;ORPHANET
Tgene	PDGFRB	C0004782	Basal Ganglia Diseases	1	CTD_human
Tgene	PDGFRB	C0006663	Calcinosis	1	CTD_human
Tgene	PDGFRB	C0015371	Extrapyramidal Disorders	1	CTD_human
Tgene	PDGFRB	C0036337	Schizoaffective Disorder	1	PSYGENET
Tgene	PDGFRB	C0206648	Myofibromatosis	1	GENOMICS_ENGLAND
Tgene	PDGFRB	C0263628	Tumoral calcinosis	1	CTD_human
Tgene	PDGFRB	C0521174	Microcalcification	1	CTD_human
Tgene	PDGFRB	C0750951	Lenticulostriate Disorders	1	CTD_human
Tgene	PDGFRB	C1333046	Myeloproliferative Neoplasm, Unclassifiable	1	ORPHANET
Tgene	PDGFRB	C1866182	Penttinen-Aula syndrome	1	CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Tgene	PDGFRB	C3472621	Myeloid neoplasm with beta-type platelet-derived growth factor receptor gene rearrangement	1	ORPHANET
Tgene	PDGFRB	C3714756	Intellectual Disability	1	GENOMICS_ENGLAND