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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:SQSTM1-NTRK1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SQSTM1-NTRK1
FusionPDB ID: 86213
FusionGDB2.0 ID: 86213
HgeneTgene
Gene symbol

SQSTM1

NTRK1

Gene ID

8878

4914

Gene namesequestosome 1neurotrophic receptor tyrosine kinase 1
SynonymsA170|DMRV|FTDALS3|NADGP|OSIL|PDB3|ZIP3|p60|p62|p62BMTC|TRK|TRK1|TRKA|Trk-A|p140-TrkA
Cytomap

5q35.3

1q23.1

Type of geneprotein-codingprotein-coding
Descriptionsequestosome-1EBI3-associated protein of 60 kDaEBI3-associated protein p60EBIAPautophagy receptor p62oxidative stress induced likephosphotyrosine independent ligand for the Lck SH2 domain p62phosphotyrosine-independent ligand for the Lck SH2 domainhigh affinity nerve growth factor receptorOncogene TRKTRK1-transforming tyrosine kinase proteingp140trkneurotrophic tyrosine kinase, receptor, type 1tropomyosin-related kinase Atyrosine kinase receptor A
Modification date2020032720200313
UniProtAcc

Q13501

Main function of 5'-partner protein: FUNCTION: Autophagy receptor required for selective macroautophagy (aggrephagy). Functions as a bridge between polyubiquitinated cargo and autophagosomes. Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family (PubMed:16286508, PubMed:20168092, PubMed:24128730, PubMed:28404643, PubMed:22622177). Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:24128730, PubMed:20168092). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357, PubMed:33393215). {ECO:0000250|UniProtKB:O08623, ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:33393215}.

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 geneENST idsENST00000360718, ENST00000376929, 
ENST00000389805, ENST00000402874, 
ENST00000510187, ENST00000506690, 
ENST00000531606, ENST00000358660, 
ENST00000368196, ENST00000392302, 
ENST00000524377, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score29 X 23 X 12=800425 X 24 X 13=7800
# samples 3333
** MAII scorelog2(33/8004*10)=-4.60018323765993
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: SQSTM1 [Title/Abstract] AND NTRK1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SQSTM1 [Title/Abstract] AND NTRK1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SQSTM1(179252226)-NTRK1(156844363), # samples:3
Anticipated loss of major functional domain due to fusion event.SQSTM1-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.
SQSTM1-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.
SQSTM1-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.
SQSTM1-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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneSQSTM1

GO:0006914

autophagy

20452972

HgeneSQSTM1

GO:0007032

endosome organization

27368102

HgeneSQSTM1

GO:0031397

negative regulation of protein ubiquitination

20452972

HgeneSQSTM1

GO:0061635

regulation of protein complex stability

25127057

HgeneSQSTM1

GO:1905719

protein localization to perinuclear region of cytoplasm

27368102

TgeneNTRK1

GO:0006468

protein phosphorylation

15488758

TgeneNTRK1

GO:0008285

negative regulation of cell proliferation

15488758

TgeneNTRK1

GO:0010976

positive regulation of neuron projection development

15488758

TgeneNTRK1

GO:0018108

peptidyl-tyrosine phosphorylation

2927393

TgeneNTRK1

GO:0043547

positive regulation of GTPase activity

15488758

TgeneNTRK1

GO:0046579

positive regulation of Ras protein signal transduction

15488758

TgeneNTRK1

GO:0046777

protein autophosphorylation

15488758

TgeneNTRK1

GO:0048011

neurotrophin TRK receptor signaling pathway

15488758

TgeneNTRK1

GO:0051092

positive regulation of NF-kappaB transcription factor activity

15488758

TgeneNTRK1

GO:0070374

positive regulation of ERK1 and ERK2 cascade

15488758

TgeneNTRK1

GO:1904646

cellular response to amyloid-beta

11927634



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/chr5:179252226/chr1:156844363)
- 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 buttonRetention 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.

check buttonFusion gene breakpoints across SQSTM1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion 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.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)
ENST00000376929SQSTM1chr5179252226+ENST00000392302NTRK1chr1156844363+22108623032057584
ENST00000376929SQSTM1chr5179252226+ENST00000368196NTRK1chr1156844363+22668623032057584
ENST00000376929SQSTM1chr5179252226+ENST00000524377NTRK1chr1156844363+20588623032057584
ENST00000376929SQSTM1chr5179252226+ENST00000358660NTRK1chr1156844363+21368623032066587
ENST00000389805SQSTM1chr5179252226+ENST00000392302NTRK1chr1156844363+22809321782127649
ENST00000389805SQSTM1chr5179252226+ENST00000368196NTRK1chr1156844363+23369321782127649
ENST00000389805SQSTM1chr5179252226+ENST00000524377NTRK1chr1156844363+21289321782127650
ENST00000389805SQSTM1chr5179252226+ENST00000358660NTRK1chr1156844363+22069321782136652
ENST00000402874SQSTM1chr5179252226+ENST00000392302NTRK1chr1156844363+2120772181967649
ENST00000402874SQSTM1chr5179252226+ENST00000368196NTRK1chr1156844363+2176772181967649
ENST00000402874SQSTM1chr5179252226+ENST00000524377NTRK1chr1156844363+1968772181967649
ENST00000402874SQSTM1chr5179252226+ENST00000358660NTRK1chr1156844363+2046772181976652
ENST00000510187SQSTM1chr5179252226+ENST00000392302NTRK1chr1156844363+2118770161965649
ENST00000510187SQSTM1chr5179252226+ENST00000368196NTRK1chr1156844363+2174770161965649
ENST00000510187SQSTM1chr5179252226+ENST00000524377NTRK1chr1156844363+1966770161965650
ENST00000510187SQSTM1chr5179252226+ENST00000358660NTRK1chr1156844363+2044770161974652
ENST00000360718SQSTM1chr5179252226+ENST00000392302NTRK1chr1156844363+237010223342217627
ENST00000360718SQSTM1chr5179252226+ENST00000368196NTRK1chr1156844363+242610223342217627
ENST00000360718SQSTM1chr5179252226+ENST00000524377NTRK1chr1156844363+221810223342217628
ENST00000360718SQSTM1chr5179252226+ENST00000358660NTRK1chr1156844363+229610223342226630
ENST00000376929SQSTM1chr5179252226+ENST00000392302NTRK1chr1156844362+22108623032057584
ENST00000376929SQSTM1chr5179252226+ENST00000368196NTRK1chr1156844362+22668623032057584
ENST00000376929SQSTM1chr5179252226+ENST00000524377NTRK1chr1156844362+20588623032057584
ENST00000376929SQSTM1chr5179252226+ENST00000358660NTRK1chr1156844362+21368623032066587
ENST00000389805SQSTM1chr5179252226+ENST00000392302NTRK1chr1156844362+22809321782127649
ENST00000389805SQSTM1chr5179252226+ENST00000368196NTRK1chr1156844362+23369321782127649
ENST00000389805SQSTM1chr5179252226+ENST00000524377NTRK1chr1156844362+21289321782127650
ENST00000389805SQSTM1chr5179252226+ENST00000358660NTRK1chr1156844362+22069321782136652
ENST00000402874SQSTM1chr5179252226+ENST00000392302NTRK1chr1156844362+2120772181967649
ENST00000402874SQSTM1chr5179252226+ENST00000368196NTRK1chr1156844362+2176772181967649
ENST00000402874SQSTM1chr5179252226+ENST00000524377NTRK1chr1156844362+1968772181967649
ENST00000402874SQSTM1chr5179252226+ENST00000358660NTRK1chr1156844362+2046772181976652
ENST00000510187SQSTM1chr5179252226+ENST00000392302NTRK1chr1156844362+2118770161965649
ENST00000510187SQSTM1chr5179252226+ENST00000368196NTRK1chr1156844362+2174770161965649
ENST00000510187SQSTM1chr5179252226+ENST00000524377NTRK1chr1156844362+1966770161965650
ENST00000510187SQSTM1chr5179252226+ENST00000358660NTRK1chr1156844362+2044770161974652
ENST00000360718SQSTM1chr5179252226+ENST00000392302NTRK1chr1156844362+237010223342217627
ENST00000360718SQSTM1chr5179252226+ENST00000368196NTRK1chr1156844362+242610223342217627
ENST00000360718SQSTM1chr5179252226+ENST00000524377NTRK1chr1156844362+221810223342217628
ENST00000360718SQSTM1chr5179252226+ENST00000358660NTRK1chr1156844362+229610223342226630

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
ENST00000376929ENST00000392302SQSTM1chr5179252226+NTRK1chr1156844363+0.0645127450.9354873
ENST00000376929ENST00000368196SQSTM1chr5179252226+NTRK1chr1156844363+0.0606006350.93939936
ENST00000376929ENST00000524377SQSTM1chr5179252226+NTRK1chr1156844363+0.0685845240.93141544
ENST00000376929ENST00000358660SQSTM1chr5179252226+NTRK1chr1156844363+0.073249240.9267508
ENST00000389805ENST00000392302SQSTM1chr5179252226+NTRK1chr1156844363+0.0147386590.9852614
ENST00000389805ENST00000368196SQSTM1chr5179252226+NTRK1chr1156844363+0.0136496170.98635036
ENST00000389805ENST00000524377SQSTM1chr5179252226+NTRK1chr1156844363+0.0169443640.9830556
ENST00000389805ENST00000358660SQSTM1chr5179252226+NTRK1chr1156844363+0.0178460630.9821539
ENST00000402874ENST00000392302SQSTM1chr5179252226+NTRK1chr1156844363+0.0155818330.98441815
ENST00000402874ENST00000368196SQSTM1chr5179252226+NTRK1chr1156844363+0.0143355740.98566437
ENST00000402874ENST00000524377SQSTM1chr5179252226+NTRK1chr1156844363+0.0179419630.98205805
ENST00000402874ENST00000358660SQSTM1chr5179252226+NTRK1chr1156844363+0.0188923070.98110765
ENST00000510187ENST00000392302SQSTM1chr5179252226+NTRK1chr1156844363+0.015511590.98448837
ENST00000510187ENST00000368196SQSTM1chr5179252226+NTRK1chr1156844363+0.0142906570.9857093
ENST00000510187ENST00000524377SQSTM1chr5179252226+NTRK1chr1156844363+0.0178570990.98214287
ENST00000510187ENST00000358660SQSTM1chr5179252226+NTRK1chr1156844363+0.0188129360.9811871
ENST00000360718ENST00000392302SQSTM1chr5179252226+NTRK1chr1156844363+0.0500214770.94997853
ENST00000360718ENST00000368196SQSTM1chr5179252226+NTRK1chr1156844363+0.0485038570.9514962
ENST00000360718ENST00000524377SQSTM1chr5179252226+NTRK1chr1156844363+0.0527624150.94723755
ENST00000360718ENST00000358660SQSTM1chr5179252226+NTRK1chr1156844363+0.058309150.9416909
ENST00000376929ENST00000392302SQSTM1chr5179252226+NTRK1chr1156844362+0.0645127450.9354873
ENST00000376929ENST00000368196SQSTM1chr5179252226+NTRK1chr1156844362+0.0606006350.93939936
ENST00000376929ENST00000524377SQSTM1chr5179252226+NTRK1chr1156844362+0.0685845240.93141544
ENST00000376929ENST00000358660SQSTM1chr5179252226+NTRK1chr1156844362+0.073249240.9267508
ENST00000389805ENST00000392302SQSTM1chr5179252226+NTRK1chr1156844362+0.0147386590.9852614
ENST00000389805ENST00000368196SQSTM1chr5179252226+NTRK1chr1156844362+0.0136496170.98635036
ENST00000389805ENST00000524377SQSTM1chr5179252226+NTRK1chr1156844362+0.0169443640.9830556
ENST00000389805ENST00000358660SQSTM1chr5179252226+NTRK1chr1156844362+0.0178460630.9821539
ENST00000402874ENST00000392302SQSTM1chr5179252226+NTRK1chr1156844362+0.0155818330.98441815
ENST00000402874ENST00000368196SQSTM1chr5179252226+NTRK1chr1156844362+0.0143355740.98566437
ENST00000402874ENST00000524377SQSTM1chr5179252226+NTRK1chr1156844362+0.0179419630.98205805
ENST00000402874ENST00000358660SQSTM1chr5179252226+NTRK1chr1156844362+0.0188923070.98110765
ENST00000510187ENST00000392302SQSTM1chr5179252226+NTRK1chr1156844362+0.015511590.98448837
ENST00000510187ENST00000368196SQSTM1chr5179252226+NTRK1chr1156844362+0.0142906570.9857093
ENST00000510187ENST00000524377SQSTM1chr5179252226+NTRK1chr1156844362+0.0178570990.98214287
ENST00000510187ENST00000358660SQSTM1chr5179252226+NTRK1chr1156844362+0.0188129360.9811871
ENST00000360718ENST00000392302SQSTM1chr5179252226+NTRK1chr1156844362+0.0500214770.94997853
ENST00000360718ENST00000368196SQSTM1chr5179252226+NTRK1chr1156844362+0.0485038570.9514962
ENST00000360718ENST00000524377SQSTM1chr5179252226+NTRK1chr1156844362+0.0527624150.94723755
ENST00000360718ENST00000358660SQSTM1chr5179252226+NTRK1chr1156844362+0.058309150.9416909

check button 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 SQSTM1-NTRK1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SQSTM1chr5179252226NTRK1chr11568443621022227LKNVGESVAAALSPLDTNSTSGDPVE
SQSTM1chr5179252226NTRK1chr1156844362770249LKNVGESVAAALSPLDTNSTSGDPVE
SQSTM1chr5179252226NTRK1chr1156844362772249LKNVGESVAAALSPLDTNSTSGDPVE
SQSTM1chr5179252226NTRK1chr1156844362862184LKNVGESVAAALSPLDTNSTSGDPVE
SQSTM1chr5179252226NTRK1chr1156844362932249LKNVGESVAAALSPLDTNSTSGDPVE
SQSTM1chr5179252226NTRK1chr11568443631022227LKNVGESVAAALSPLDTNSTSGDPVE
SQSTM1chr5179252226NTRK1chr1156844363770249LKNVGESVAAALSPLDTNSTSGDPVE
SQSTM1chr5179252226NTRK1chr1156844363772249LKNVGESVAAALSPLDTNSTSGDPVE
SQSTM1chr5179252226NTRK1chr1156844363862184LKNVGESVAAALSPLDTNSTSGDPVE
SQSTM1chr5179252226NTRK1chr1156844363932249LKNVGESVAAALSPLDTNSTSGDPVE

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Potential FusionNeoAntigen Information of SQSTM1-NTRK1 in HLA I

check button 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.

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Potential FusionNeoAntigen Information of SQSTM1-NTRK1 in HLA II

check button 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.
SQSTM1-NTRK1_179252226_156844362.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0403GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0405GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0411GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0411VGESVAAALSPLDTN318
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0413AAALSPLDTNSTSGD823
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0417GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0417VGESVAAALSPLDTN318
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0429GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0430GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0439GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0440AAALSPLDTNSTSGD823
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0441GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0444AAALSPLDTNSTSGD823
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0445GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0446GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0448GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0449GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0452GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0455AAALSPLDTNSTSGD823
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0456AAALSPLDTNSTSGD823
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0457GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0460GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0467GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0467VGESVAAALSPLDTN318
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0468AAALSPLDTNSTSGD823
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0470AAALSPLDTNSTSGD823
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0471GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0477GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0479AAALSPLDTNSTSGD823
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0483GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0484GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0485GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0489GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0491GESVAAALSPLDTNS419
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-0491VGESVAAALSPLDTN318
SQSTM1-NTRK1chr5179252226chr11568443621022DRB1-1410GESVAAALSPLDTNS419

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Fusion breakpoint peptide structures of SQSTM1-NTRK1

check button3D 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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SQSTM1-NTRK1

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score

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Vaccine Design for the FusionNeoAntigens of SQSTM1-NTRK1

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SQSTM1-NTRK1chr5179252226chr1156844362318VGESVAAALSPLDTNAGAGTGTGGCAGCTGCCCTTAGCCCTCTGGACACTAACAGCACAT
SQSTM1-NTRK1chr5179252226chr1156844362419GESVAAALSPLDTNSGTGTGGCAGCTGCCCTTAGCCCTCTGGACACTAACAGCACATCTG
SQSTM1-NTRK1chr5179252226chr1156844362823AAALSPLDTNSTSGDCCCTTAGCCCTCTGGACACTAACAGCACATCTGGAGACCCGGTGG

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Information of the samples that have these potential fusion neoantigens of SQSTM1-NTRK1

check button 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 typeFusion geneHchrHbpHenstTchrTbpTenstSample

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Potential target of CAR-T therapy development for SQSTM1-NTRK1

check button Predicted 3D structure. We used RoseTTAFold.

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, 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'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneNTRK1chr5:179252226chr1:156844362ENST00000368196716424_4390791.0TransmembraneHelical
TgeneNTRK1chr5:179252226chr1:156844362ENST00000392302817424_4390761.0TransmembraneHelical
TgeneNTRK1chr5:179252226chr1:156844362ENST00000524377817424_4390797.0TransmembraneHelical
TgeneNTRK1chr5:179252226chr1:156844363ENST00000368196716424_4390791.0TransmembraneHelical
TgeneNTRK1chr5:179252226chr1:156844363ENST00000392302817424_4390761.0TransmembraneHelical
TgeneNTRK1chr5:179252226chr1:156844363ENST00000524377817424_4390797.0TransmembraneHelical

check button 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.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to SQSTM1-NTRK1

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

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Related Diseases to SQSTM1-NTRK1

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

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneSQSTM1C4085252PAGET DISEASE OF BONE 39GENOMICS_ENGLAND;UNIPROT
HgeneSQSTM1C0002736Amyotrophic Lateral Sclerosis5CTD_human;ORPHANET
HgeneSQSTM1C4225326FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 34CTD_human;UNIPROT
HgeneSQSTM1C0029463Osteosarcoma2GENOMICS_ENGLAND
HgeneSQSTM1C0221054Welander Distal Myopathy1ORPHANET
HgeneSQSTM1C0242383Age related macular degeneration1CTD_human
HgeneSQSTM1C0393554Amyotrophic Lateral Sclerosis With Dementia1CTD_human
HgeneSQSTM1C0543859Amyotrophic Lateral Sclerosis, Guam Form1CTD_human
HgeneSQSTM1C1853926NONAKA MYOPATHY1CTD_human;GENOMICS_ENGLAND
HgeneSQSTM1C2931290Welander distal myopathy, Swedish type1ORPHANET
HgeneSQSTM1C3888102Frontotemporal Dementia With Motor Neuron Disease1ORPHANET
HgeneSQSTM1C4011788Behavioral variant of frontotemporal dementia1ORPHANET
TgeneNTRK1C0020074HSAN Type IV17CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneNTRK1C0238463Papillary thyroid carcinoma3ORPHANET
TgeneNTRK1C0002768Congenital Pain Insensitivity1ORPHANET
TgeneNTRK1C0005586Bipolar Disorder1CTD_human
TgeneNTRK1C0005587Depression, Bipolar1CTD_human
TgeneNTRK1C0017638Glioma1CTD_human
TgeneNTRK1C0020075Hereditary Sensory Autonomic Neuropathy, Type 51CTD_human;ORPHANET
TgeneNTRK1C0024713Manic Disorder1CTD_human
TgeneNTRK1C0027796Neuralgia1CTD_human
TgeneNTRK1C0027819Neuroblastoma1CTD_human
TgeneNTRK1C0033958Psychosis, Brief Reactive1CTD_human
TgeneNTRK1C0033975Psychotic Disorders1CTD_human
TgeneNTRK1C0036337Schizoaffective Disorder1CTD_human
TgeneNTRK1C0036341Schizophrenia1CTD_human
TgeneNTRK1C0036358Schizophreniform Disorders1CTD_human
TgeneNTRK1C0038870Neuralgia, Supraorbital1CTD_human
TgeneNTRK1C0042656Neuralgia, Vidian1CTD_human
TgeneNTRK1C0234247Neuralgia, Atypical1CTD_human
TgeneNTRK1C0234249Neuralgia, Stump1CTD_human
TgeneNTRK1C0259783mixed gliomas1CTD_human
TgeneNTRK1C0273115Lung Injury1CTD_human
TgeneNTRK1C0338831Manic1CTD_human
TgeneNTRK1C0423711Neuralgia, Perineal1CTD_human
TgeneNTRK1C0423712Neuralgia, Iliohypogastric Nerve1CTD_human
TgeneNTRK1C0555198Malignant Glioma1CTD_human
TgeneNTRK1C0598589Inherited neuropathies1GENOMICS_ENGLAND
TgeneNTRK1C0751371Neuralgia, Ilioinguinal1CTD_human
TgeneNTRK1C0751372Nerve Pain1CTD_human
TgeneNTRK1C0751373Paroxysmal Nerve Pain1CTD_human
TgeneNTRK1C0752347Lewy Body Disease1CTD_human
TgeneNTRK1C1833921Familial medullary thyroid carcinoma1CTD_human;GENOMICS_ENGLAND;ORPHANET
TgeneNTRK1C2350344Chronic Lung Injury1CTD_human