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Fusion Protein:TPM4-NTRK1

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: TPM4-NTRK1
	FusionPDB ID: 93411
	FusionGDB2.0 ID: 93411
		Hgene	Tgene
	Gene symbol	TPM4	NTRK1
	Gene ID	7171	4914
	Gene name	tropomyosin 4	neurotrophic receptor tyrosine kinase 1
	Synonyms	HEL-S-108	MTC\|TRK\|TRK1\|TRKA\|Trk-A\|p140-TrkA
	Cytomap	19p13.12-p13.11	1q23.1
	Type of gene	protein-coding	protein-coding
	Description	tropomyosin alpha-4 chainTM30p1epididymis secretory protein Li 108	high affinity nerve growth factor receptorOncogene TRKTRK1-transforming tyrosine kinase proteingp140trkneurotrophic tyrosine kinase, receptor, type 1tropomyosin-related kinase Atyrosine kinase receptor A
	Modification date	20200320	20200313
	UniProtAcc	P67936 Main function of 5'-partner protein: FUNCTION: Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments (By similarity). Binds calcium (PubMed:1836432). {ECO:0000250\|UniProtKB:P09495, ECO:0000269\|PubMed:1836432}.	P04629 Main function of 5'-partner protein: FUNCTION: Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1850821, PubMed:1849459, PubMed:1281417, PubMed:8325889, PubMed:15488758, PubMed:22649032, PubMed:17196528, PubMed:27445338). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. {ECO:0000250\|UniProtKB:P35739, ECO:0000250\|UniProtKB:Q3UFB7, ECO:0000269\|PubMed:11244088, ECO:0000269\|PubMed:1281417, ECO:0000269\|PubMed:15488758, ECO:0000269\|PubMed:17196528, ECO:0000269\|PubMed:1849459, ECO:0000269\|PubMed:1850821, ECO:0000269\|PubMed:22649032, ECO:0000269\|PubMed:27445338, ECO:0000269\|PubMed:27676246, ECO:0000269\|PubMed:8155326, ECO:0000269\|PubMed:8325889}.; FUNCTION: [Isoform TrkA-III]: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed. {ECO:0000269\|PubMed:15488758}.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000591645, ENST00000300933, ENST00000344824, ENST00000538887,	ENST00000358660, ENST00000368196, ENST00000392302, ENST00000524377, ENST00000531606,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	22 X 19 X 9=3762	25 X 24 X 13=7800
	# samples	25	33
	** MAII score	log2(25/3762*10)=-3.91149984886111 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(33/7800*10)=-4.56293619439116 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: TPM4 [Title/Abstract] AND NTRK1 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: TPM4 [Title/Abstract] AND NTRK1 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	TPM4(16204563)-NTRK1(156845311), # samples:1 TPM4(16204563)-NTRK1(156845871), # samples:1 TPM4(16204563)-NTRK1(156844362), # samples:1
Anticipated loss of major functional domain due to fusion event.	TPM4-NTRK1 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. TPM4-NTRK1 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. TPM4-NTRK1 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. TPM4-NTRK1 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
Tgene	NTRK1	GO:0006468	protein phosphorylation	15488758
Tgene	NTRK1	GO:0008285	negative regulation of cell proliferation	15488758
Tgene	NTRK1	GO:0010976	positive regulation of neuron projection development	15488758
Tgene	NTRK1	GO:0018108	peptidyl-tyrosine phosphorylation	2927393
Tgene	NTRK1	GO:0043547	positive regulation of GTPase activity	15488758
Tgene	NTRK1	GO:0046579	positive regulation of Ras protein signal transduction	15488758
Tgene	NTRK1	GO:0046777	protein autophosphorylation	15488758
Tgene	NTRK1	GO:0048011	neurotrophin TRK receptor signaling pathway	15488758
Tgene	NTRK1	GO:0051092	positive regulation of NF-kappaB transcription factor activity	15488758
Tgene	NTRK1	GO:0070374	positive regulation of ERK1 and ERK2 cascade	15488758
Tgene	NTRK1	GO:1904646	cellular response to amyloid-beta	11927634

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:16204563/chr1:156845311)
- 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.

Retention analysis results 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, are available here.

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 NTRK1 (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 Amino Acid Sequences

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)
ENST00000344824	TPM4	chr19	16204563	+	ENST00000392302	NTRK1	chr1	156845311	+	2079	890	58	1926	622
ENST00000344824	TPM4	chr19	16204563	+	ENST00000368196	NTRK1	chr1	156845311	+	2135	890	58	1926	622
ENST00000344824	TPM4	chr19	16204563	+	ENST00000524377	NTRK1	chr1	156845311	+	1927	890	58	1926	623
ENST00000344824	TPM4	chr19	16204563	+	ENST00000358660	NTRK1	chr1	156845311	+	2005	890	58	1935	625
ENST00000538887	TPM4	chr19	16204563	+	ENST00000392302	NTRK1	chr1	156845311	+	2048	859	27	1895	622
ENST00000538887	TPM4	chr19	16204563	+	ENST00000368196	NTRK1	chr1	156845311	+	2104	859	27	1895	622
ENST00000538887	TPM4	chr19	16204563	+	ENST00000524377	NTRK1	chr1	156845311	+	1896	859	27	1895	622
ENST00000538887	TPM4	chr19	16204563	+	ENST00000358660	NTRK1	chr1	156845311	+	1974	859	27	1904	625
ENST00000300933	TPM4	chr19	16204563	+	ENST00000392302	NTRK1	chr1	156845311	+	2113	924	29	1960	643
ENST00000300933	TPM4	chr19	16204563	+	ENST00000368196	NTRK1	chr1	156845311	+	2169	924	29	1960	643
ENST00000300933	TPM4	chr19	16204563	+	ENST00000524377	NTRK1	chr1	156845311	+	1961	924	29	1960	644
ENST00000300933	TPM4	chr19	16204563	+	ENST00000358660	NTRK1	chr1	156845311	+	2039	924	29	1969	646
ENST00000344824	TPM4	chr19	16204563	+	ENST00000392302	NTRK1	chr1	156845871	+	1932	890	58	1779	573
ENST00000344824	TPM4	chr19	16204563	+	ENST00000368196	NTRK1	chr1	156845871	+	1988	890	58	1779	573
ENST00000344824	TPM4	chr19	16204563	+	ENST00000524377	NTRK1	chr1	156845871	+	1780	890	58	1779	574
ENST00000344824	TPM4	chr19	16204563	+	ENST00000358660	NTRK1	chr1	156845871	+	1849	890	58	1779	573
ENST00000538887	TPM4	chr19	16204563	+	ENST00000392302	NTRK1	chr1	156845871	+	1901	859	27	1748	573
ENST00000538887	TPM4	chr19	16204563	+	ENST00000368196	NTRK1	chr1	156845871	+	1957	859	27	1748	573
ENST00000538887	TPM4	chr19	16204563	+	ENST00000524377	NTRK1	chr1	156845871	+	1749	859	27	1748	573
ENST00000538887	TPM4	chr19	16204563	+	ENST00000358660	NTRK1	chr1	156845871	+	1818	859	27	1748	573
ENST00000300933	TPM4	chr19	16204563	+	ENST00000392302	NTRK1	chr1	156845871	+	1966	924	29	1813	594
ENST00000300933	TPM4	chr19	16204563	+	ENST00000368196	NTRK1	chr1	156845871	+	2022	924	29	1813	594
ENST00000300933	TPM4	chr19	16204563	+	ENST00000524377	NTRK1	chr1	156845871	+	1814	924	29	1813	595
ENST00000300933	TPM4	chr19	16204563	+	ENST00000358660	NTRK1	chr1	156845871	+	1883	924	29	1813	594
ENST00000344824	TPM4	chr19	16204563	+	ENST00000392302	NTRK1	chr1	156844362	+	2238	890	58	2085	675
ENST00000344824	TPM4	chr19	16204563	+	ENST00000368196	NTRK1	chr1	156844362	+	2294	890	58	2085	675
ENST00000344824	TPM4	chr19	16204563	+	ENST00000524377	NTRK1	chr1	156844362	+	2086	890	58	2085	676
ENST00000344824	TPM4	chr19	16204563	+	ENST00000358660	NTRK1	chr1	156844362	+	2164	890	58	2094	678
ENST00000538887	TPM4	chr19	16204563	+	ENST00000392302	NTRK1	chr1	156844362	+	2207	859	27	2054	675
ENST00000538887	TPM4	chr19	16204563	+	ENST00000368196	NTRK1	chr1	156844362	+	2263	859	27	2054	675
ENST00000538887	TPM4	chr19	16204563	+	ENST00000524377	NTRK1	chr1	156844362	+	2055	859	27	2054	675
ENST00000538887	TPM4	chr19	16204563	+	ENST00000358660	NTRK1	chr1	156844362	+	2133	859	27	2063	678
ENST00000300933	TPM4	chr19	16204563	+	ENST00000392302	NTRK1	chr1	156844362	+	2272	924	29	2119	696
ENST00000300933	TPM4	chr19	16204563	+	ENST00000368196	NTRK1	chr1	156844362	+	2328	924	29	2119	696
ENST00000300933	TPM4	chr19	16204563	+	ENST00000524377	NTRK1	chr1	156844362	+	2120	924	29	2119	697
ENST00000300933	TPM4	chr19	16204563	+	ENST00000358660	NTRK1	chr1	156844362	+	2198	924	29	2128	699

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
ENST00000344824	ENST00000392302	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.008812213	0.9911878
ENST00000344824	ENST00000368196	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.008390485	0.9916095
ENST00000344824	ENST00000524377	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.008906594	0.99109346
ENST00000344824	ENST00000358660	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.009621481	0.9903785
ENST00000538887	ENST00000392302	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.008879779	0.9911203
ENST00000538887	ENST00000368196	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.008409904	0.9915901
ENST00000538887	ENST00000524377	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.009016261	0.9909837
ENST00000538887	ENST00000358660	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.009684945	0.990315
ENST00000300933	ENST00000392302	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.012892977	0.987107
ENST00000300933	ENST00000368196	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.012581601	0.9874184
ENST00000300933	ENST00000524377	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.01334206	0.9866579
ENST00000300933	ENST00000358660	TPM4	chr19	16204563	+	NTRK1	chr1	156845311	+	0.014596606	0.9854034
ENST00000344824	ENST00000392302	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.006403816	0.9935962
ENST00000344824	ENST00000368196	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.006257534	0.9937424
ENST00000344824	ENST00000524377	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.006509149	0.9934909
ENST00000344824	ENST00000358660	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.006396844	0.99360317
ENST00000538887	ENST00000392302	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.006495504	0.9935045
ENST00000538887	ENST00000368196	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.006186881	0.99381316
ENST00000538887	ENST00000524377	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.0065583	0.9934417
ENST00000538887	ENST00000358660	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.006496291	0.99350375
ENST00000300933	ENST00000392302	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.010059488	0.98994046
ENST00000300933	ENST00000368196	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.009582909	0.9904171
ENST00000300933	ENST00000524377	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.010041977	0.989958
ENST00000300933	ENST00000358660	TPM4	chr19	16204563	+	NTRK1	chr1	156845871	+	0.009984542	0.99001545
ENST00000344824	ENST00000392302	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.012606453	0.9873935
ENST00000344824	ENST00000368196	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.012219594	0.98778045
ENST00000344824	ENST00000524377	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.013045374	0.9869546
ENST00000344824	ENST00000358660	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.012486731	0.98751324
ENST00000538887	ENST00000392302	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.012536842	0.9874631
ENST00000538887	ENST00000368196	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.012154347	0.9878456
ENST00000538887	ENST00000524377	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.012998179	0.9870018
ENST00000538887	ENST00000358660	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.01242334	0.9875766
ENST00000300933	ENST00000392302	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.015559483	0.98444057
ENST00000300933	ENST00000368196	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.014842508	0.9851575
ENST00000300933	ENST00000524377	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.016557984	0.983442
ENST00000300933	ENST00000358660	TPM4	chr19	16204563	+	NTRK1	chr1	156844362	+	0.015467046	0.984533

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

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for TPM4-NTRK1

+/-13 AA sequence from the breakpoints of the fusion protein sequences.

Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	Length(fusion protein)	BP in fusion protein	Peptide
TPM4	chr19	16204563	NTRK1	chr1	156844362	859	277	TVAKLEKTIDDLEDTNSTSGDPVEKK
TPM4	chr19	16204563	NTRK1	chr1	156844362	890	277	TVAKLEKTIDDLEDTNSTSGDPVEKK
TPM4	chr19	16204563	NTRK1	chr1	156844362	924	298	TVAKLEKTIDDLEDTNSTSGDPVEKK
TPM4	chr19	16204563	NTRK1	chr1	156845311	859	277	TVAKLEKTIDDLEGPAVLAPEDGLAM
TPM4	chr19	16204563	NTRK1	chr1	156845311	890	277	TVAKLEKTIDDLEGPAVLAPEDGLAM
TPM4	chr19	16204563	NTRK1	chr1	156845311	924	298	TVAKLEKTIDDLEGPAVLAPEDGLAM
TPM4	chr19	16204563	NTRK1	chr1	156845871	859	277	TVAKLEKTIDDLEGVHHIKRRDIVLK
TPM4	chr19	16204563	NTRK1	chr1	156845871	890	277	TVAKLEKTIDDLEGVHHIKRRDIVLK
TPM4	chr19	16204563	NTRK1	chr1	156845871	924	298	TVAKLEKTIDDLEGVHHIKRRDIVLK

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Potential FusionNeoAntigen Information of TPM4-NTRK1 in HLA I

Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

TPM4-NTRK1_16204563_156845311.msa
TPM4-NTRK1_16204563_156845871.msa

Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)

Fusion gene	Hchr	Hbp	Tgene	Tchr	Tbp	HLA I	FusionNeoAntigen peptide	Binding score	Immunogenic score	Neoantigen start (at BP 13)	Neoantigen end (at BP 13)
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-B45:01	LEGPAVLAP	0.9905	0.9889	11	20
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-B50:02	LEGPAVLAP	0.9772	0.8097	11	20
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-B41:01	LEGPAVLAP	0.4767	0.992	11	20
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-B50:01	LEGPAVLAP	0.4746	0.906	11	20
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-A02:21	KTIDDLEGPAV	0.9887	0.785	6	17
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-A02:20	KTIDDLEGPAV	0.9731	0.7009	6	17
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-B40:06	LEGPAVLAP	0.9932	0.9683	11	20
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-B39:08	IDDLEGPAVL	0.9331	0.9019	8	18
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-C05:09	TIDDLEGPAVL	1	0.9539	7	18
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-C08:15	TIDDLEGPAVL	1	0.9813	7	18
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-B50:05	LEGPAVLAP	0.4746	0.906	11	20
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-B50:04	LEGPAVLAP	0.4746	0.906	11	20
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-B18:08	DDLEGPAVL	0.3455	0.9448	9	18
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-B18:03	DDLEGPAVL	0.3317	0.9516	9	18
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-C04:03	TIDDLEGPAVL	1	0.907	7	18
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-C05:01	TIDDLEGPAVL	1	0.9539	7	18
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-C08:02	TIDDLEGPAVL	1	0.9813	7	18
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-A02:06	KTIDDLEGPAV	0.9887	0.785	6	17
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	HLA-A02:14	KTIDDLEGPAV	0.9886	0.6723	6	17
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:38	KTIDDLEGV	0.9866	0.7403	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:21	KTIDDLEGV	0.9837	0.8233	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:35	KTIDDLEGV	0.9815	0.7634	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:22	KTIDDLEGV	0.98	0.5593	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:11	KTIDDLEGV	0.9767	0.7597	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:60	KTIDDLEGV	0.9767	0.7138	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:04	KTIDDLEGV	0.9759	0.738	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:30	KTIDDLEGV	0.9758	0.7374	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:67	KTIDDLEGV	0.9758	0.7374	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:24	KTIDDLEGV	0.9758	0.7374	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:29	KTIDDLEGV	0.966	0.7392	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:20	KTIDDLEGV	0.9634	0.7428	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:27	KTIDDLEGV	0.9614	0.6856	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:16	KTIDDLEGV	0.9586	0.7245	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:13	KTIDDLEGV	0.9087	0.7593	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-B51:07	DDLEGVHHI	0.9831	0.7667	9	18
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:01	KTIDDLEGV	0.9758	0.7374	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:07	KTIDDLEGV	0.9752	0.7341	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:14	KTIDDLEGV	0.9845	0.6636	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:06	KTIDDLEGV	0.9837	0.8233	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A02:03	KTIDDLEGV	0.9506	0.7221	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A68:02	KTIDDLEGV	0.9342	0.5992	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A69:01	KTIDDLEGV	0.9105	0.8646	6	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A68:02	EKTIDDLEGV	0.7843	0.706	5	15
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	HLA-A69:01	EKTIDDLEGV	0.6499	0.8482	5	15

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Potential FusionNeoAntigen Information of TPM4-NTRK1 in HLA II

TPM4-NTRK1_16204563_156845311.msa
TPM4-NTRK1_16204563_156845871.msa

Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).

Fusion gene	Hchr	Hbp	Tgene	Tchr	Tbp	HLA II	FusionNeoAntigen peptide	Neoantigen start (at BP 13)	Neoantigen end (at BP 13)
TPM4-NTRK1	chr19	16204563	chr1	156845311	924	DRB1-0102	EKTIDDLEGPAVLAP	5	20
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	DRB1-1354	LEGVHHIKRRDIVLK	11	26
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	DRB1-1354	DLEGVHHIKRRDIVL	10	25
TPM4-NTRK1	chr19	16204563	chr1	156845871	924	DRB1-1354	DDLEGVHHIKRRDIV	9	24

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Fusion breakpoint peptide structures of TPM4-NTRK1

3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.

File name	BPseq	Hgene	Tgene	Hchr	Hbp	Tchr	Tbp	AAlen
4632	KTIDDLEGPAVLAP	TPM4	NTRK1	chr19	16204563	chr1	156845311	924

File name	BPseq	Hgene	Tgene	Hchr	Hbp	Tchr	Tbp	AAlen
4633	KTIDDLEGVHHIKR	TPM4	NTRK1	chr19	16204563	chr1	156845871	924

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TPM4-NTRK1

Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.

HLA allele	PDB ID	File name	BPseq	Docking score	Glide score
HLA-B14:02	3BVN	4632	KTIDDLEGPAVLAP	-7.15543	-7.26883
HLA-B14:02	3BVN	4632	KTIDDLEGPAVLAP	-4.77435	-5.80965
HLA-B52:01	3W39	4632	KTIDDLEGPAVLAP	-6.80875	-6.92215
HLA-B52:01	3W39	4632	KTIDDLEGPAVLAP	-4.20386	-5.23916
HLA-A11:01	4UQ2	4632	KTIDDLEGPAVLAP	-7.5194	-8.5547
HLA-A11:01	4UQ2	4632	KTIDDLEGPAVLAP	-6.9601	-7.0735
HLA-A24:02	5HGA	4632	KTIDDLEGPAVLAP	-7.52403	-7.63743
HLA-A24:02	5HGA	4632	KTIDDLEGPAVLAP	-5.82433	-6.85963
HLA-B27:05	6PYJ	4632	KTIDDLEGPAVLAP	-3.28285	-4.31815
HLA-B44:05	3DX8	4632	KTIDDLEGPAVLAP	-5.91172	-6.94702
HLA-B44:05	3DX8	4632	KTIDDLEGPAVLAP	-4.24346	-4.35686
HLA-B14:02	3BVN	4633	KTIDDLEGVHHIKR	-7.15543	-7.26883
HLA-B14:02	3BVN	4633	KTIDDLEGVHHIKR	-4.77435	-5.80965
HLA-B52:01	3W39	4633	KTIDDLEGVHHIKR	-6.80875	-6.92215
HLA-B52:01	3W39	4633	KTIDDLEGVHHIKR	-4.20386	-5.23916
HLA-A11:01	4UQ2	4633	KTIDDLEGVHHIKR	-7.5194	-8.5547
HLA-A11:01	4UQ2	4633	KTIDDLEGVHHIKR	-6.9601	-7.0735
HLA-A24:02	5HGA	4633	KTIDDLEGVHHIKR	-7.52403	-7.63743
HLA-A24:02	5HGA	4633	KTIDDLEGVHHIKR	-5.82433	-6.85963
HLA-B27:05	6PYJ	4633	KTIDDLEGVHHIKR	-3.28285	-4.31815
HLA-B44:05	3DX8	4633	KTIDDLEGVHHIKR	-5.91172	-6.94702
HLA-B44:05	3DX8	4633	KTIDDLEGVHHIKR	-4.24346	-4.35686

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Vaccine Design for the FusionNeoAntigens of TPM4-NTRK1

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.

Fusion gene	Hchr	Hbp	Tchr	Tbp	Start in +/-13AA	End in +/-13AA	FusionNeoAntigen peptide sequence	FusionNeoAntigen RNA sequence
TPM4-NTRK1	chr19	16204563	chr1	156845311	11	20	LEGPAVLAP	TGGAAGGCCCGGCTGTGCTGGCTCCAG
TPM4-NTRK1	chr19	16204563	chr1	156845311	6	17	KTIDDLEGPAV	AGACAATTGATGACCTGGAAGGCCCGGCTGTGC
TPM4-NTRK1	chr19	16204563	chr1	156845311	7	18	TIDDLEGPAVL	CAATTGATGACCTGGAAGGCCCGGCTGTGCTGG
TPM4-NTRK1	chr19	16204563	chr1	156845311	8	18	IDDLEGPAVL	TTGATGACCTGGAAGGCCCGGCTGTGCTGG
TPM4-NTRK1	chr19	16204563	chr1	156845311	9	18	DDLEGPAVL	ATGACCTGGAAGGCCCGGCTGTGCTGG
TPM4-NTRK1	chr19	16204563	chr1	156845871	5	15	EKTIDDLEGV	AAAAGACAATTGATGACCTGGAAGGTGTTC
TPM4-NTRK1	chr19	16204563	chr1	156845871	6	15	KTIDDLEGV	AGACAATTGATGACCTGGAAGGTGTTC
TPM4-NTRK1	chr19	16204563	chr1	156845871	9	18	DDLEGVHHI	ATGACCTGGAAGGTGTTCACCACATCA

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.

Fusion gene	Hchr	Hbp	Tchr	Tbp	Start in +/-13AA	End in +/-13AA	FusionNeoAntigen peptide	FusionNEoAntigen RNA sequence
TPM4-NTRK1	chr19	16204563	chr1	156845311	5	20	EKTIDDLEGPAVLAP	AAAAGACAATTGATGACCTGGAAGGCCCGGCTGTGCTGGCTCCAG
TPM4-NTRK1	chr19	16204563	chr1	156845871	10	25	DLEGVHHIKRRDIVL	ACCTGGAAGGTGTTCACCACATCAAGCGCCGGGACATCGTGCTCA
TPM4-NTRK1	chr19	16204563	chr1	156845871	11	26	LEGVHHIKRRDIVLK	TGGAAGGTGTTCACCACATCAAGCGCCGGGACATCGTGCTCAAGT
TPM4-NTRK1	chr19	16204563	chr1	156845871	9	24	DDLEGVHHIKRRDIV	ATGACCTGGAAGGTGTTCACCACATCAAGCGCCGGGACATCGTGC

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Information of the samples that have these potential fusion neoantigens of TPM4-NTRK1

These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.

Cancer type	Fusion gene	Hchr	Hbp	Henst	Tchr	Tbp	Tenst	Sample
SARC	TPM4-NTRK1	chr19	16204563	ENST00000300933	chr1	156845311	ENST00000358660	TCGA-DX-A3UA
SARC	TPM4-NTRK1	chr19	16204563	ENST00000300933	chr1	156845871	ENST00000358660	TCGA-DX-A3UA

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Potential target of CAR-T therapy development for TPM4-NTRK1

Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features

* Minus value of BPloci means that the break point is located before the CDS.

- In-frame and retained 'Transmembrane'.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

NTRK1

chr19:16204563

chr1:156844362

ENST00000368196

424_439

791.0

Transmembrane

Helical

Tgene

NTRK1

chr19:16204563

chr1:156844362

ENST00000392302

424_439

761.0

Transmembrane

Helical

Tgene

NTRK1

chr19:16204563

chr1:156844362

ENST00000524377

424_439

797.0

Transmembrane

Helical

Tgene

NTRK1

chr19:16204563

chr1:156845311

ENST00000392302

424_439

761.0

Transmembrane

Helical

Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.

Hgene

Hchr

Hbp

Henst

Tgene

Tchr

Tbp

Tenst

DeepLoc result

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Related Drugs to TPM4-NTRK1

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 TPM4-NTRK1

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	TPM4	C0001787	Osteoporosis, Age-Related	1	CTD_human
Hgene	TPM4	C0003949	Asbestosis	1	CTD_human
Hgene	TPM4	C0005818	Blood Platelet Disorders	1	GENOMICS_ENGLAND
Hgene	TPM4	C0014859	Esophageal Neoplasms	1	CTD_human
Hgene	TPM4	C0023893	Liver Cirrhosis, Experimental	1	CTD_human
Hgene	TPM4	C0027627	Neoplasm Metastasis	1	CTD_human
Hgene	TPM4	C0029456	Osteoporosis	1	CTD_human
Hgene	TPM4	C0029459	Osteoporosis, Senile	1	CTD_human
Hgene	TPM4	C0032927	Precancerous Conditions	1	CTD_human
Hgene	TPM4	C0043094	Weight Gain	1	CTD_human
Hgene	TPM4	C0282313	Condition, Preneoplastic	1	CTD_human
Hgene	TPM4	C0334121	Inflammatory Myofibroblastic Tumor	1	ORPHANET
Hgene	TPM4	C0546837	Malignant neoplasm of esophagus	1	CTD_human
Hgene	TPM4	C0751406	Post-Traumatic Osteoporosis	1	CTD_human
Hgene	TPM4	C0948089	Acute Coronary Syndrome	1	CTD_human
Hgene	TPM4	C2751260	Macrothrombocytopenia	1	GENOMICS_ENGLAND
Hgene	TPM4	C2930617	Pulmonary Fibrosis - from Asbestos Exposure	1	CTD_human
Hgene	TPM4	C4304021	Autosomal dominant macrothrombocytopenia	1	ORPHANET
Tgene	NTRK1	C0020074	HSAN Type IV	17	CTD_human;GENOMICS_ENGLAND;UNIPROT
Tgene	NTRK1	C0238463	Papillary thyroid carcinoma	3	ORPHANET
Tgene	NTRK1	C0002768	Congenital Pain Insensitivity	1	ORPHANET
Tgene	NTRK1	C0005586	Bipolar Disorder	1	CTD_human
Tgene	NTRK1	C0005587	Depression, Bipolar	1	CTD_human
Tgene	NTRK1	C0017638	Glioma	1	CTD_human
Tgene	NTRK1	C0020075	Hereditary Sensory Autonomic Neuropathy, Type 5	1	CTD_human;ORPHANET
Tgene	NTRK1	C0024713	Manic Disorder	1	CTD_human
Tgene	NTRK1	C0027796	Neuralgia	1	CTD_human
Tgene	NTRK1	C0027819	Neuroblastoma	1	CTD_human
Tgene	NTRK1	C0033958	Psychosis, Brief Reactive	1	CTD_human
Tgene	NTRK1	C0033975	Psychotic Disorders	1	CTD_human
Tgene	NTRK1	C0036337	Schizoaffective Disorder	1	CTD_human
Tgene	NTRK1	C0036341	Schizophrenia	1	CTD_human
Tgene	NTRK1	C0036358	Schizophreniform Disorders	1	CTD_human
Tgene	NTRK1	C0038870	Neuralgia, Supraorbital	1	CTD_human
Tgene	NTRK1	C0042656	Neuralgia, Vidian	1	CTD_human
Tgene	NTRK1	C0234247	Neuralgia, Atypical	1	CTD_human
Tgene	NTRK1	C0234249	Neuralgia, Stump	1	CTD_human
Tgene	NTRK1	C0259783	mixed gliomas	1	CTD_human
Tgene	NTRK1	C0273115	Lung Injury	1	CTD_human
Tgene	NTRK1	C0338831	Manic	1	CTD_human
Tgene	NTRK1	C0423711	Neuralgia, Perineal	1	CTD_human
Tgene	NTRK1	C0423712	Neuralgia, Iliohypogastric Nerve	1	CTD_human
Tgene	NTRK1	C0555198	Malignant Glioma	1	CTD_human
Tgene	NTRK1	C0598589	Inherited neuropathies	1	GENOMICS_ENGLAND
Tgene	NTRK1	C0751371	Neuralgia, Ilioinguinal	1	CTD_human
Tgene	NTRK1	C0751372	Nerve Pain	1	CTD_human
Tgene	NTRK1	C0751373	Paroxysmal Nerve Pain	1	CTD_human
Tgene	NTRK1	C0752347	Lewy Body Disease	1	CTD_human
Tgene	NTRK1	C1833921	Familial medullary thyroid carcinoma	1	CTD_human;GENOMICS_ENGLAND;ORPHANET
Tgene	NTRK1	C2350344	Chronic Lung Injury	1	CTD_human

	Fusion Gene and Fusion Protein Summary
	Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)
	Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)
	Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)
	Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)
	Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)
	Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)
	Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)
	Potential target of CAR-T therapy development
	Information on the samples that have these potential fusion neoantigens
	Fusion Protein Targeting Drugs - (Manual Curation)
	Fusion Protein Related diseases - (Manual Curation)