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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:TTLL3-TGFB1

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: TTLL3-TGFB1
	FusionPDB ID: 95163
	FusionGDB2.0 ID: 95163
		Hgene	Tgene
	Gene symbol	TTLL3	TGFB1
	Gene ID	26140	7040
	Gene name	tubulin tyrosine ligase like 3	transforming growth factor beta 1
	Synonyms	HOTTL	CED\|DPD1\|IBDIMDE\|LAP\|TGF-beta1\|TGFB\|TGFbeta
	Cytomap	3p25.3	19q13.2
	Type of gene	protein-coding	protein-coding
	Description	tubulin monoglycylase TTLL3tubulin tyrosine ligase-like family, member 3tubulin--tyrosine ligase-like protein 3	transforming growth factor beta-1 proproteinTGF-beta-1latency-associated peptideprepro-transforming growth factor beta-1transforming growth factor beta1
	Modification date	20200313	20200329
	UniProtAcc	.	TIAF1
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000397241, ENST00000427853, ENST00000426895, ENST00000547186, ENST00000383827, ENST00000430793, ENST00000455274, ENST00000466245,	ENST00000221930,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	5 X 5 X 3=75	8 X 6 X 7=336
	# samples	5	8
	** MAII score	log2(5/75*10)=-0.584962500721156 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(8/336*10)=-2.0703893278914 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: TTLL3 [Title/Abstract] AND TGFB1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	TTLL3(9859443)-TGFB1(41854360), # samples:1
Anticipated loss of major functional domain due to fusion event.	TTLL3-TGFB1 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. TTLL3-TGFB1 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. TTLL3-TGFB1 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. TTLL3-TGFB1 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	TTLL3	GO:0018094	protein polyglycylation	19524510
Tgene	TGFB1	GO:0001837	epithelial to mesenchymal transition	25893292\|29529050
Tgene	TGFB1	GO:0001933	negative regulation of protein phosphorylation	8053900
Tgene	TGFB1	GO:0001934	positive regulation of protein phosphorylation	18625725
Tgene	TGFB1	GO:0002062	chondrocyte differentiation	15040835
Tgene	TGFB1	GO:0002244	hematopoietic progenitor cell differentiation	15451575
Tgene	TGFB1	GO:0006611	protein export from nucleus	9770491\|17438144\|18588859
Tgene	TGFB1	GO:0006754	ATP biosynthetic process	10513816
Tgene	TGFB1	GO:0006796	phosphate-containing compound metabolic process	10513816
Tgene	TGFB1	GO:0006954	inflammatory response	21147091
Tgene	TGFB1	GO:0007050	cell cycle arrest	14555988
Tgene	TGFB1	GO:0007093	mitotic cell cycle checkpoint	15334054
Tgene	TGFB1	GO:0007173	epidermal growth factor receptor signaling pathway	18625725
Tgene	TGFB1	GO:0007179	transforming growth factor beta receptor signaling pathway	9389648\|11157754
Tgene	TGFB1	GO:0007182	common-partner SMAD protein phosphorylation	20573232
Tgene	TGFB1	GO:0007183	SMAD protein complex assembly	17438144
Tgene	TGFB1	GO:0008284	positive regulation of cell proliferation	10513816\|14633705
Tgene	TGFB1	GO:0008285	negative regulation of cell proliferation	15334054
Tgene	TGFB1	GO:0010628	positive regulation of gene expression	18625725\|18832382\|18941241\|19913496\|25322725\|26634652\|26687115\|27162619\|29167509
Tgene	TGFB1	GO:0010629	negative regulation of gene expression	19913496\|20067797\|22269326\|25163461\|26634652\|29167509\|29529050
Tgene	TGFB1	GO:0010718	positive regulation of epithelial to mesenchymal transition	17999987\|18505915
Tgene	TGFB1	GO:0010763	positive regulation of fibroblast migration	18555217
Tgene	TGFB1	GO:0010800	positive regulation of peptidyl-threonine phosphorylation	18625725\|19736306
Tgene	TGFB1	GO:0010862	positive regulation of pathway-restricted SMAD protein phosphorylation	9389648\|19736306\|26634652
Tgene	TGFB1	GO:0010936	negative regulation of macrophage cytokine production	20875417
Tgene	TGFB1	GO:0016477	cell migration	25893292
Tgene	TGFB1	GO:0017015	regulation of transforming growth factor beta receptor signaling pathway	15334054
Tgene	TGFB1	GO:0022408	negative regulation of cell-cell adhesion	18593713
Tgene	TGFB1	GO:0030214	hyaluronan catabolic process	17324121
Tgene	TGFB1	GO:0030308	negative regulation of cell growth	15334054
Tgene	TGFB1	GO:0030335	positive regulation of cell migration	19736306
Tgene	TGFB1	GO:0031293	membrane protein intracellular domain proteolysis	25310401
Tgene	TGFB1	GO:0031334	positive regulation of protein complex assembly	19366691
Tgene	TGFB1	GO:0031663	lipopolysaccharide-mediated signaling pathway	21147091
Tgene	TGFB1	GO:0032270	positive regulation of cellular protein metabolic process	15219857
Tgene	TGFB1	GO:0032355	response to estradiol	18039789
Tgene	TGFB1	GO:0032570	response to progesterone	18039789
Tgene	TGFB1	GO:0032740	positive regulation of interleukin-17 production	18453574
Tgene	TGFB1	GO:0032801	receptor catabolic process	17878231
Tgene	TGFB1	GO:0032930	positive regulation of superoxide anion generation	22073128
Tgene	TGFB1	GO:0032967	positive regulation of collagen biosynthetic process	19734317\|22269326\|25310401
Tgene	TGFB1	GO:0033138	positive regulation of peptidyl-serine phosphorylation	18625725\|19736306
Tgene	TGFB1	GO:0035307	positive regulation of protein dephosphorylation	14555988
Tgene	TGFB1	GO:0042307	positive regulation of protein import into nucleus	19366691
Tgene	TGFB1	GO:0043117	positive regulation of vascular permeability	21168935
Tgene	TGFB1	GO:0043406	positive regulation of MAP kinase activity	18625725
Tgene	TGFB1	GO:0043536	positive regulation of blood vessel endothelial cell migration	18555217
Tgene	TGFB1	GO:0043537	negative regulation of blood vessel endothelial cell migration	18555217
Tgene	TGFB1	GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity	18625725
Tgene	TGFB1	GO:0045216	cell-cell junction organization	18505915
Tgene	TGFB1	GO:0045599	negative regulation of fat cell differentiation	15040835
Tgene	TGFB1	GO:0045662	negative regulation of myoblast differentiation	9770491
Tgene	TGFB1	GO:0045786	negative regulation of cell cycle	11502704
Tgene	TGFB1	GO:0045892	negative regulation of transcription, DNA-templated	15702480\|18832382
Tgene	TGFB1	GO:0045893	positive regulation of transcription, DNA-templated	9389648\|14517293\|15334054\|16816361
Tgene	TGFB1	GO:0045918	negative regulation of cytolysis	24586048
Tgene	TGFB1	GO:0045930	negative regulation of mitotic cell cycle	14555988
Tgene	TGFB1	GO:0045944	positive regulation of transcription by RNA polymerase II	18832382
Tgene	TGFB1	GO:0048298	positive regulation of isotype switching to IgA isotypes	14988498
Tgene	TGFB1	GO:0048642	negative regulation of skeletal muscle tissue development	9770491
Tgene	TGFB1	GO:0050680	negative regulation of epithelial cell proliferation	9950587
Tgene	TGFB1	GO:0050714	positive regulation of protein secretion	18505915
Tgene	TGFB1	GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation	21168935
Tgene	TGFB1	GO:0050921	positive regulation of chemotaxis	18555217
Tgene	TGFB1	GO:0051897	positive regulation of protein kinase B signaling	18625725
Tgene	TGFB1	GO:0060389	pathway-restricted SMAD protein phosphorylation	11157754\|17999987\|18453574\|25893292
Tgene	TGFB1	GO:0060390	regulation of SMAD protein signal transduction	25893292
Tgene	TGFB1	GO:0060391	positive regulation of SMAD protein signal transduction	9389648\|19366691\|29167509
Tgene	TGFB1	GO:0070168	negative regulation of biomineral tissue development	26634652
Tgene	TGFB1	GO:0070374	positive regulation of ERK1 and ERK2 cascade	25310401
Tgene	TGFB1	GO:0070723	response to cholesterol	17878231
Tgene	TGFB1	GO:0071407	cellular response to organic cyclic compound	21147091
Tgene	TGFB1	GO:0071560	cellular response to transforming growth factor beta stimulus	19736306\|22269326
Tgene	TGFB1	GO:0085029	extracellular matrix assembly	19734317
Tgene	TGFB1	GO:0090263	positive regulation of canonical Wnt signaling pathway	12893825\|15040835
Tgene	TGFB1	GO:0097191	extrinsic apoptotic signaling pathway	15334054
Tgene	TGFB1	GO:1900126	negative regulation of hyaluronan biosynthetic process	17324121
Tgene	TGFB1	GO:1900182	positive regulation of protein localization to nucleus	26634652
Tgene	TGFB1	GO:1901666	positive regulation of NAD+ ADP-ribosyltransferase activity	22073128
Tgene	TGFB1	GO:1902895	positive regulation of pri-miRNA transcription by RNA polymerase II	26311719\|26493107
Tgene	TGFB1	GO:1903077	negative regulation of protein localization to plasma membrane	21168935\|24586048
Tgene	TGFB1	GO:1903800	positive regulation of production of miRNAs involved in gene silencing by miRNA	18548003
Tgene	TGFB1	GO:2000679	positive regulation of transcription regulatory region DNA binding	22073128
Tgene	TGFB1	GO:2000727	positive regulation of cardiac muscle cell differentiation	25163461

Fusion gene breakpoints across TTLL3 (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 TGFB1 (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	KIRC	TCGA-A3-3306-01A	TTLL3	chr3	9859443	+	TGFB1	chr19	41854360	-

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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)

ENST00000426895

TTLL3

chr3

9859443

ENST00000221930

TGFB1

chr19

41854360

2425

878

1695

558

ENST00000547186

TTLL3

chr3

9859443

ENST00000221930

TGFB1

chr19

41854360

2193

646

1463

459

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
ENST00000426895	ENST00000221930	TTLL3	chr3	9859443	+	TGFB1	chr19	41854360	-	0.03782389	0.9621761
ENST00000547186	ENST00000221930	TTLL3	chr3	9859443	+	TGFB1	chr19	41854360	-	0.007845259	0.9921548

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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

>95163_95163_1_TTLL3-TGFB1_TTLL3_chr3_9859443_ENST00000426895_TGFB1_chr19_41854360_ENST00000221930_length(amino acids)=558AA_BP=286
MQGPDAPLLLSARELGPGRRGSASWYRQEGGAVCNWLRKPQPLEPRTSFPSARRSEFRPPRRLPWAGPASAQSEEGHAGGRCQAGSPAPA
RRLSGAFKTLVPGTHAQGASDTHPLGPPHTPVLDPSPQDGFPVLWRGSSKASHMNRLRNAKIYVERAVKQKKIFTIQGCYPVIRCLLRRR
GWVEKKMVHRSGPTLLPPQKDLDSSAMGDSDTTEDEDEDEDEEFQPSQLFDFDDLLKFDDLDGTHALMVGLCLNLRNLPWFDEVDANSFF
PRCYCLGAEDDKKAFIEIYDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWRYLSNRLLAPSDS
PEWLSFDVTGVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFTTGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDT
NYCFSSTEKNCCVRQLYIDFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQALEPLPIVYYVGR

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

>95163_95163_2_TTLL3-TGFB1_TTLL3_chr3_9859443_ENST00000547186_TGFB1_chr19_41854360_ENST00000221930_length(amino acids)=459AA_BP=187
MVPGTHAQGASDTHPLGPPHTPVLDPSPQDGFPVLWRGSSKASHMNRLRNAKIYVERAVKQKKIFTIQGCYPVIRCLLRRRGWVEKKMVH
RSGPTLLPPQKDLDSSAMGDSDTTEDEDEDEDEEFQPSQLFDFDDLLKFDDLDGTHALMVGLCLNLRNLPWFDEVDANSFFPRCYCLGAE
DDKKAFIEIYDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWRYLSNRLLAPSDSPEWLSFDVT
GVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFTTGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDTNYCFSSTEK
NCCVRQLYIDFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQALEPLPIVYYVGRKPKVEQLSN

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

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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/chr3:9859443/chr19:41854360)
- 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
.	TGFB1 TIAF1
FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.	115

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

Tgene

TGFB1

chr3:9859443

chr19:41854360

ENST00000221930

244_246

118.33333333333333

391.0

Motif

Cell attachment site

Tgene

TGFB1

chr3:9859443

chr19:41854360

ENST00000221930

226_252

118.33333333333333

391.0

Region

Bowtie tail

- 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

TTLL3

chr3:9859443

chr19:41854360

ENST00000383827

151_510

353.0

Domain

TTL

Hgene

TTLL3

chr3:9859443

chr19:41854360

ENST00000397241

151_510

714.6666666666666

Domain

TTL

Hgene

TTLL3

chr3:9859443

chr19:41854360

ENST00000427853

151_510

353.0

Domain

TTL

Hgene

TTLL3

chr3:9859443

chr19:41854360

ENST00000430793

151_510

435.0

Domain

TTL

Hgene

TTLL3

chr3:9859443

chr19:41854360

ENST00000547186

151_510

143.33333333333334

773.0

Domain

TTL

Hgene

TTLL3

chr3:9859443

chr19:41854360

ENST00000383827

321_324

353.0

Nucleotide binding

ATP binding

Hgene

TTLL3

chr3:9859443

chr19:41854360

ENST00000397241

321_324

714.6666666666666

Nucleotide binding

ATP binding

Hgene

TTLL3

chr3:9859443

chr19:41854360

ENST00000427853

321_324

353.0

Nucleotide binding

ATP binding

Hgene

TTLL3

chr3:9859443

chr19:41854360

ENST00000430793

321_324

435.0

Nucleotide binding

ATP binding

Hgene

TTLL3

chr3:9859443

chr19:41854360

ENST00000547186

321_324

143.33333333333334

773.0

Nucleotide binding

ATP binding

Tgene

TGFB1

chr3:9859443

chr19:41854360

ENST00000221930

30_74

118.33333333333333

391.0

Region

Straightjacket domain

Tgene

TGFB1

chr3:9859443

chr19:41854360

ENST00000221930

75_271

118.33333333333333

391.0

Region

Arm domain

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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
TTLL3
TGFB1

- 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 TTLL3-TGFB1

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 TTLL3-TGFB1

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