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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
	Related Drugs
	Related Diseases

Fusion gene:TPM4-KLF2 (FusionGDB2 ID:93408)

Fusion Gene Summary for TPM4-KLF2

Fusion gene summary

Fusion gene information	Fusion gene name: TPM4-KLF2
	Fusion gene ID: 93408
		Hgene	Tgene
	Gene symbol	TPM4	KLF2
	Gene ID	7171	10365
	Gene name	tropomyosin 4	Kruppel like factor 2
	Synonyms	HEL-S-108	LKLF
	Cytomap	19p13.12-p13.11	19p13.11
	Type of gene	protein-coding	protein-coding
	Description	tropomyosin alpha-4 chainTM30p1epididymis secretory protein Li 108	Krueppel-like factor 2Kruppel-like factor 2 (lung)Kruppel-like factor LKLFlung Kruppel-like factorlung Kruppel-like zinc finger transcription factorlung krueppel-like factor
	Modification date	20200320	20200313
	UniProtAcc	.	.
	Ensembl transtripts involved in fusion gene	ENST00000300933, ENST00000344824, ENST00000538887, ENST00000591645,	ENST00000248071, ENST00000592003,
Fusion gene scores	* DoF score	22 X 19 X 9=3762	3 X 3 X 2=18
	# samples	25	4
	** MAII score	log2(25/3762*10)=-3.91149984886111 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(4/18*10)=1.15200309344505 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Context	PubMed: TPM4 [Title/Abstract] AND KLF2 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	TPM4(16187507)-KLF2(16437666), # 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)

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
Tgene	KLF2	GO:0000122	negative regulation of transcription by RNA polymerase II	26299712
Tgene	KLF2	GO:0045429	positive regulation of nitric oxide biosynthetic process	21768538
Tgene	KLF2	GO:0045893	positive regulation of transcription, DNA-templated	21063504
Tgene	KLF2	GO:0048386	positive regulation of retinoic acid receptor signaling pathway	26416422

Fusion 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.

Fusion gene breakpoints across KLF2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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	LAML	TCGA-AB-2944	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+

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Fusion Gene ORF analysis for TPM4-KLF2

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.

ORF	Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
In-frame	ENST00000300933	ENST00000248071	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+
In-frame	ENST00000300933	ENST00000592003	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+
intron-3CDS	ENST00000344824	ENST00000248071	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+
intron-3CDS	ENST00000344824	ENST00000592003	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+
intron-3CDS	ENST00000538887	ENST00000248071	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+
intron-3CDS	ENST00000538887	ENST00000592003	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+
intron-3CDS	ENST00000591645	ENST00000248071	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+
intron-3CDS	ENST00000591645	ENST00000592003	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+

ORFfinder result based on the fusion transcript sequence of in-frame fusion genes.

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)

ENST00000300933

TPM4

chr19

16187507

ENST00000248071

KLF2

chr19

16437666

1411

392

1057

455

200

ENST00000300933

TPM4

chr19

16187507

ENST00000592003

KLF2

chr19

16437666

797

392

553

174

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
ENST00000300933	ENST00000248071	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+	0.74224174	0.25775832
ENST00000300933	ENST00000592003	TPM4	chr19	16187507	+	KLF2	chr19	16437666	+	0.3589152	0.64108473

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Fusion Genomic Features for TPM4-KLF2

FusionAI 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.

Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	1-p	p (fusion gene breakpoint)
TPM4	chr19	16187507	+	KLF2	chr19	16437666	+	2.09E-06	0.99999785
TPM4	chr19	16187507	+	KLF2	chr19	16437666	+	2.09E-06	0.99999785

Distribution 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.

Distribution 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-KLF2

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:16187507/chr19:16437666)
- 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
.	.
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: 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}.

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.

- In-frame and 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

Tgene

KLF2

chr19:16187507

chr19:16437666

ENST00000248071

302_326

297

356.0

Zinc finger

C2H2-type 2

Tgene

KLF2

chr19:16187507

chr19:16437666

ENST00000248071

332_354

297

356.0

Zinc finger

C2H2-type 3

- In-frame and 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

TPM4

chr19:16187507

chr19:16437666

ENST00000300933

2_248

249.0

Coiled coil

Ontology_term=ECO:0000250

Hgene

TPM4

chr19:16187507

chr19:16437666

ENST00000344824

2_248

285.0

Coiled coil

Ontology_term=ECO:0000250

Hgene

TPM4

chr19:16187507

chr19:16437666

ENST00000538887

2_248

270.0

Coiled coil

Ontology_term=ECO:0000250

Tgene

KLF2

chr19:16187507

chr19:16437666

ENST00000248071

130_135

297

356.0

Compositional bias

Note=Poly-Gly

Tgene

KLF2

chr19:16187507

chr19:16437666

ENST00000248071

167_171

297

356.0

Compositional bias

Note=Poly-Pro

Tgene

KLF2

chr19:16187507

chr19:16437666

ENST00000248071

225_231

297

356.0

Compositional bias

Note=Poly-Ala

Tgene

KLF2

chr19:16187507

chr19:16437666

ENST00000248071

62_71

297

356.0

Compositional bias

Note=Poly-Pro

Tgene

KLF2

chr19:16187507

chr19:16437666

ENST00000248071

43_51

297

356.0

Motif

9aaTAD

Tgene

KLF2

chr19:16187507

chr19:16437666

ENST00000248071

272_296

297

356.0

Zinc finger

C2H2-type 1

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Fusion Gene Sequence for TPM4-KLF2

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.

>93408_93408_1_TPM4-KLF2_TPM4_chr19_16187507_ENST00000300933_KLF2_chr19_16437666_ENST00000248071_length(transcript)=1411nt_BP=392nt
AAGTCCCGAAAAGGGGCACTTTCCAGCAGCTGTGGCCAGCGGTGCCGACGTCAGGCCCTCCCCCAGCGGTGCTGACGTCGGCGGTCCGGC
CGGGTGACCTCATCGCCCCGACGGCAGCCGGCCCGGGGGGCGGGGAGAGGCGGGGGCGGCCCCCGCGCAGGCAAAGGCTTGGGGGGCCGG
GGCGCGGCTGTGCAGCTCTCGCCGGAGCCGAGCCCAGCCGAGCGTCCGCCGCTGCCCGTGCGCCTCTGCGCCTCCGCGCCATGGCCGGCC
TCAACTCCCTGGAGGCGGTGAAACGCAAGATCCAGGCCCTGCAGCAGCAGGCGGACGAGGCGGAAGACCGCGCGCAGGGCCTGCAGCGGG
AGCTGGACGGCGAGCGCGAGCGGCGCGAGAAAGTGAGAAGCCCTACCACTGCAACTGGGACGGCTGCGGCTGGAAGTTTGCGCGCTCAGA
CGAGCTCACGCGCCACTACCGAAAGCACACGGGCCACCGGCCATTCCAGTGCCATCTGTGCGATCGTGCCTTCTCGCGCTCCGATCACCT
GGCGCTGCACATGAAACGGCACATGTAGCCGGGACGCCCCCGCCCACCTGCGCGCGGCCGTGGCGGGTCCCACGCGCCGGGCGCGGCCCC
CTCCCAAACTGTGACTGGTATTTATTGGACCCAGAGAACCGGGCCGGGCACAGCGTGGCTACAGAGGGTCTCCCTCGATGACGACGACGA
CGACGCCACCACCCCAGCCCCCGTCTGTGACTGAAGGCCCGGTGGGAAAAGACCACGATCCTCCTTGACGAGTTTTGTTTTTCAAAATGG
TGCAATAATTTAAGTGGCATCTTCTCTCCCACCGGGTCTACACTAGAGGATCGAGGCTTGTGATGCCTTGTGAGAAATAAGGGCCTTAAT
TTGTACTGTCTGCGGCATTTTTTATAATATTGTATATAGTGACTGACAAATATTGTATTACTGTACATAGAGAGACAGGTGGGCATTTTT
GGGCTACCTGGTTCGTTTTTATAAGATTTTGCTGGGTTGGTTTTTTTTTTAATTAAAAAGTTTTGCATCTTTTAAAAAAAATCACAGCAC
TGGTCTGGTTGCTTGGAACTGGGGCCTTGGGGCACTTGGGAGGAGGGGGGAGCGGAGAGTTTGATGGAGGGCAGCCCCACTAAAGCATCG
TGTGCAGTGGGTCCTGCGTCTGCCAGCACCGGGACTGCCAGCTGCTGTGCCTGCCTGCCAGGAACCTGTGGGTTTTTCTGTAAATTTAGA
CACTGCATTTTAGGACTGAGGGAGGGTTATTTTAAGGTTGTTCTTTGAGCCATAAATTGCCTCTTTGCCCCACAGCTGGGGAAAGTGCTG

>93408_93408_1_TPM4-KLF2_TPM4_chr19_16187507_ENST00000300933_KLF2_chr19_16437666_ENST00000248071_length(amino acids)=200AA_BP=
MQNFLIKKKTNPAKSYKNEPGSPKMPTCLSMYSNTIFVSHYIQYYKKCRRQYKLRPLFLTRHHKPRSSSVDPVGEKMPLKLLHHFEKQNS
SRRIVVFSHRAFSHRRGLGWWRRRRRHRGRPSVATLCPARFSGSNKYQSQFGRGPRPARGTRHGRAQVGGGVPATCAVSCAAPGDRSARR

--------------------------------------------------------------
>93408_93408_2_TPM4-KLF2_TPM4_chr19_16187507_ENST00000300933_KLF2_chr19_16437666_ENST00000592003_length(transcript)=797nt_BP=392nt
AAGTCCCGAAAAGGGGCACTTTCCAGCAGCTGTGGCCAGCGGTGCCGACGTCAGGCCCTCCCCCAGCGGTGCTGACGTCGGCGGTCCGGC
CGGGTGACCTCATCGCCCCGACGGCAGCCGGCCCGGGGGGCGGGGAGAGGCGGGGGCGGCCCCCGCGCAGGCAAAGGCTTGGGGGGCCGG
GGCGCGGCTGTGCAGCTCTCGCCGGAGCCGAGCCCAGCCGAGCGTCCGCCGCTGCCCGTGCGCCTCTGCGCCTCCGCGCCATGGCCGGCC
TCAACTCCCTGGAGGCGGTGAAACGCAAGATCCAGGCCCTGCAGCAGCAGGCGGACGAGGCGGAAGACCGCGCGCAGGGCCTGCAGCGGG
AGCTGGACGGCGAGCGCGAGCGGCGCGAGAAAGTGAGAAGCCCTACCACTGCAACTGGGACGGCTGCGGCTGGAAGTTTGCGCGCTCAGA
CGAGCTCACGCGCCACTACCGAAAGCACACGGGCCACCGGCCATTCCAGTGCCATCTGTGCGATCGTGCCTTCTCGCGCTCCGATCACCT
GGCGCTGCACATGAAACGGCACATGTAGCCGGGACGCCCCCGCCCACCTGCGCGCGGCCGTGGCGGGTCCCACGCGCCGGGCGCGGCCCC
CTCCCAAACTGTGACTGGTATTTATTGGACCCAGAGAACCGGGCCGGGCACAGCGTGGCTACAGAGGGTCTCCCTCGATGACGACGACGA

>93408_93408_2_TPM4-KLF2_TPM4_chr19_16187507_ENST00000300933_KLF2_chr19_16437666_ENST00000592003_length(amino acids)=174AA_BP=1
MWPAVPTSGPPPAVLTSAVRPGDLIAPTAAGPGGGERRGRPPRRQRLGGPGRGCAALAGAEPSRASAAARAPLRLRAMAGLNSLEAVKRK

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

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Fusion Gene PPI Analysis for TPM4-KLF2

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 (BIOGRID-3.4.160)

Hgene

Hgene's interactors

Tgene

Tgene's interactors

- Retained PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost PPIs in in-frame fusion.

Partner	Gene	Hbp	Tbp	ENST	Strand	BPexon	TotalExon	Protein feature loci	*BPloci	TotalLen	Interaction lost with
Tgene	KLF2	chr19:16187507	chr19:16437666	ENST00000248071		1	3	111_268	297.3333333333333	356.0	WWP1

- Retained PPIs, but lost function due to frame-shift fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs for TPM4-KLF2

Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)

Partner

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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Related Diseases for TPM4-KLF2

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source