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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:NTN4-LETMD1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NTN4-LETMD1
FusionPDB ID: 60680
FusionGDB2.0 ID: 60680
HgeneTgene
Gene symbol

NTN4

LETMD1

Gene ID

59277

25875

Gene namenetrin 4LETM1 domain containing 1
SynonymsPRO30911110019O13Rik|HCCR|HCCR-1|HCCR-2|HCCR1|HCCR2|HCRR-2|SLC55A3
Cytomap

12q22

12q13.12

Type of geneprotein-codingprotein-coding
Descriptionnetrin-4beta-netrinhepar-derived netrin-like proteinLETM1 domain-containing protein 1cervical cancer 1 proto-oncogene protein p40cervical cancer proto-oncogene 2 proteinepididymis secretory sperm binding proteinhuman cervical cancer oncogeneregulator of TP53
Modification date2020031320200322
UniProtAcc.

Q6P1Q0

Main function of 5'-partner protein: FUNCTION: Involved in tumorigenesis and may function as a negative regulator of the p53/TP53. {ECO:0000269|PubMed:12879013}.
Ensembl transtripts involved in fusion geneENST idsENST00000343702, ENST00000344911, 
ENST00000538383, ENST00000553059, 
ENST00000552603, 
ENST00000380123, 
ENST00000418425, ENST00000547008, 
ENST00000548516, ENST00000552739, 
ENST00000262055, ENST00000550929, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 10 X 5=5505 X 3 X 4=60
# samples 115
** MAII scorelog2(11/550*10)=-2.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/60*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NTN4 [Title/Abstract] AND LETMD1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NTN4 [Title/Abstract] AND LETMD1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NTN4(96180717)-LETMD1(51450133), # samples:2
Anticipated loss of major functional domain due to fusion event.NTN4-LETMD1 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.
NTN4-LETMD1 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.
NTN4-LETMD1 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.
NTN4-LETMD1 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.
NTN4-LETMD1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NTN4-LETMD1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted 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


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/chr12:96180717/chr12:51450133)
- 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 NTN4 (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 LETMD1 (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)
ENST00000343702NTN4chr1296180717-ENST00000550929LETMD1chr1251450133+172910341131354413
ENST00000343702NTN4chr1296180717-ENST00000262055LETMD1chr1251450133+234510341131354413
ENST00000344911NTN4chr1296180717-ENST00000550929LETMD1chr1251450133+126657143891282
ENST00000344911NTN4chr1296180717-ENST00000262055LETMD1chr1251450133+188257143891282
ENST00000553059NTN4chr1296180717-ENST00000550929LETMD1chr1251450133+12805850905301
ENST00000553059NTN4chr1296180717-ENST00000262055LETMD1chr1251450133+18965850905301

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
ENST00000343702ENST00000550929NTN4chr1296180717-LETMD1chr1251450133+0.034666680.9653334
ENST00000343702ENST00000262055NTN4chr1296180717-LETMD1chr1251450133+0.024121120.9758789
ENST00000344911ENST00000550929NTN4chr1296180717-LETMD1chr1251450133+0.0586184750.94138145
ENST00000344911ENST00000262055NTN4chr1296180717-LETMD1chr1251450133+0.031731070.968269
ENST00000553059ENST00000550929NTN4chr1296180717-LETMD1chr1251450133+0.036975860.9630242
ENST00000553059ENST00000262055NTN4chr1296180717-LETMD1chr1251450133+0.013420160.98657984

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 NTN4-LETMD1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NTN4chr1296180717LETMD1chr12514501331034307SKYSSPFPCTGGEKALSRAMLLTSYL
NTN4chr1296180717LETMD1chr1251450133571176SKYSSPFPCTGGEKALSRAMLLTSYL
NTN4chr1296180717LETMD1chr1251450133585195SKYSSPFPCTGGEKALSRAMLLTSYL

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Potential FusionNeoAntigen Information of NTN4-LETMD1 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.
NTN4-LETMD1_96180717_51450133.msa

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)
NTN4-LETMD1chr1296180717chr12514501331034HLA-B14:01EKALSRAML0.99370.67871221
NTN4-LETMD1chr1296180717chr12514501331034HLA-B14:02EKALSRAML0.99370.67871221
NTN4-LETMD1chr1296180717chr12514501331034HLA-B40:01GEKALSRAM0.99320.571120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B44:03GEKALSRAM0.99070.98131120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B56:01FPCTGGEKA0.98620.6875615
NTN4-LETMD1chr1296180717chr12514501331034HLA-B47:01GEKALSRAM0.8850.74851120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B50:02GEKALSRAM0.84710.7861120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B18:01GEKALSRAM0.7930.90361120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B41:02GEKALSRAM0.70930.50451120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B15:03GEKALSRAM0.160.80971120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B39:13GEKALSRAM0.15360.97761120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B50:01GEKALSRAM0.05150.86181120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B35:03FPCTGGEKAL0.97370.8796616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B35:04FPCTGGEKAL0.92380.9812616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B35:02FPCTGGEKAL0.92380.9812616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B81:01FPCTGGEKAL0.58070.6225616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B82:01FPCTGGEKAL0.3680.6031616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B56:01SPFPCTGGEKA0.99550.5816415
NTN4-LETMD1chr1296180717chr12514501331034HLA-B40:06GEKALSRAM0.99650.84351120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B54:01FPCTGGEKA0.99490.8898615
NTN4-LETMD1chr1296180717chr12514501331034HLA-B40:03GEKALSRAM0.99340.57851120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B44:09GEKALSRAM0.99240.55991120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B48:03GEKALSRAM0.99220.61841120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B78:01FPCTGGEKA0.48650.8554615
NTN4-LETMD1chr1296180717chr12514501331034HLA-B39:08GEKALSRAM0.35280.9411120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B14:03EKALSRAML0.27080.86391221
NTN4-LETMD1chr1296180717chr12514501331034HLA-B56:04FPCTGGEKAL0.94130.8529616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B35:12FPCTGGEKAL0.92380.9812616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B39:10FPCTGGEKAL0.87060.9825616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B42:01FPCTGGEKAL0.79410.8575616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B54:01SPFPCTGGEKA0.99940.7799415
NTN4-LETMD1chr1296180717chr12514501331034HLA-B40:04GEKALSRAM0.9950.92361120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B40:36GEKALSRAM0.99320.56711120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B40:12GEKALSRAM0.99220.61841120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B40:49GEKALSRAM0.99160.5671120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B44:13GEKALSRAM0.99070.98131120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B44:07GEKALSRAM0.99070.98131120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B44:26GEKALSRAM0.99070.98131120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B55:02FPCTGGEKA0.96190.7576615
NTN4-LETMD1chr1296180717chr12514501331034HLA-B56:05FPCTGGEKA0.82830.761615
NTN4-LETMD1chr1296180717chr12514501331034HLA-B18:06GEKALSRAM0.79330.92741120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B18:05GEKALSRAM0.7930.90361120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B18:03GEKALSRAM0.77610.89911120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B18:11GEKALSRAM0.75490.88811120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B41:03GEKALSRAM0.52010.79821120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B15:53GEKALSRAM0.42710.86371120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B78:02FPCTGGEKA0.39180.9487615
NTN4-LETMD1chr1296180717chr12514501331034HLA-B15:54GEKALSRAM0.33690.85841120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B15:68GEKALSRAM0.33120.74191120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B48:02GEKALSRAM0.08930.92961120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B50:04GEKALSRAM0.05150.86181120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B50:05GEKALSRAM0.05150.86181120
NTN4-LETMD1chr1296180717chr12514501331034HLA-B35:13FPCTGGEKAL0.97260.8829616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B55:04FPCTGGEKAL0.96330.8796616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B56:02FPCTGGEKAL0.94130.8529616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B35:09FPCTGGEKAL0.92380.9812616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B35:22FPCTGGEKAL0.88970.8248616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B67:01FPCTGGEKAL0.88170.9761616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B82:02FPCTGGEKAL0.3680.6031616
NTN4-LETMD1chr1296180717chr12514501331034HLA-B55:02SPFPCTGGEKA0.99840.601415

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Potential FusionNeoAntigen Information of NTN4-LETMD1 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.

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)

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Fusion breakpoint peptide structures of NTN4-LETMD1

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.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
2491FPCTGGEKALSRAMNTN4LETMD1chr1296180717chr12514501331034

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NTN4-LETMD1

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
HLA-B14:023BVN2491FPCTGGEKALSRAM-7.9962-8.1096
HLA-B14:023BVN2491FPCTGGEKALSRAM-5.70842-6.74372
HLA-B52:013W392491FPCTGGEKALSRAM-6.83737-6.95077
HLA-B52:013W392491FPCTGGEKALSRAM-4.4836-5.5189
HLA-A11:014UQ22491FPCTGGEKALSRAM-10.0067-10.1201
HLA-A11:014UQ22491FPCTGGEKALSRAM-9.03915-10.0745
HLA-A24:025HGA2491FPCTGGEKALSRAM-6.56204-6.67544
HLA-A24:025HGA2491FPCTGGEKALSRAM-5.42271-6.45801
HLA-B44:053DX82491FPCTGGEKALSRAM-7.85648-8.89178
HLA-B44:053DX82491FPCTGGEKALSRAM-5.3978-5.5112
HLA-A02:016TDR2491FPCTGGEKALSRAM-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NTN4-LETMD1

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
NTN4-LETMD1chr1296180717chr12514501331120GEKALSRAMGGAGAGAAAGCCTTGAGCCGGGCCATG
NTN4-LETMD1chr1296180717chr12514501331221EKALSRAMLGAGAAAGCCTTGAGCCGGGCCATGCTT
NTN4-LETMD1chr1296180717chr1251450133415SPFPCTGGEKAAGTCCTTTTCCATGCACTGGAGGAGAGAAAGCC
NTN4-LETMD1chr1296180717chr1251450133615FPCTGGEKATTTCCATGCACTGGAGGAGAGAAAGCC
NTN4-LETMD1chr1296180717chr1251450133616FPCTGGEKALTTTCCATGCACTGGAGGAGAGAAAGCCTTG

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

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Information of the samples that have these potential fusion neoantigens of NTN4-LETMD1

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
SARCNTN4-LETMD1chr1296180717ENST00000343702chr1251450133ENST00000262055TCGA-DX-AB2G-01A

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Potential target of CAR-T therapy development for NTN4-LETMD1

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

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 NTN4-LETMD1

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 NTN4-LETMD1

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