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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:TRIT1-ADH1B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRIT1-ADH1B
FusionPDB ID: 94266
FusionGDB2.0 ID: 94266
HgeneTgene
Gene symbol

TRIT1

ADH1B

Gene ID

54802

125

Gene nametRNA isopentenyltransferase 1alcohol dehydrogenase 1B (class I), beta polypeptide
SynonymsCOXPD35|GRO1|IPPT|IPT|IPTase|MOD5|hGRO1ADH2|HEL-S-117
Cytomap

1p34.2

4q23

Type of geneprotein-codingprotein-coding
DescriptiontRNA dimethylallyltransferaseIPP transferaseisopentenyl-diphosphate:tRNA isopentenyltransferasetRNA dimethylallyltransferase, mitochondrialtRNA isopentenylpyrophosphate transferaseall-trans-retinol dehydrogenase [NAD(+)] ADH1BADH, beta subunitalcohol dehydrogenase 2 (class I), beta polypeptidealcohol dehydrogenase subunit betaaldehyde reductaseepididymis secretory protein Li 117
Modification date2020031320200313
UniProtAcc.

P00325

Main function of 5'-partner protein: FUNCTION: Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism (PubMed:15369820, PubMed:16787387). In vitro can also catalyzes the NADH-dependent reduction of all-trans-retinal and its derivatives such as all-trans-4-oxoretinal (PubMed:15369820, PubMed:16787387). Catalyzes in the oxidative direction with higher efficiency (PubMed:16787387). Has the same affinity for all-trans-4-hydroxyretinol and all-trans-4-oxoretinal (PubMed:15369820). {ECO:0000269|PubMed:15369820, ECO:0000269|PubMed:16787387}.
Ensembl transtripts involved in fusion geneENST idsENST00000316891, ENST00000372818, 
ENST00000441669, ENST00000544981, 
ENST00000491865, ENST00000537223, 
ENST00000537440, ENST00000541099, 
ENST00000545233, 
ENST00000394887, 
ENST00000504498, ENST00000305046, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 2 X 4=562 X 2 X 2=8
# samples 62
** MAII scorelog2(6/56*10)=0.0995356735509144
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: TRIT1 [Title/Abstract] AND ADH1B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TRIT1 [Title/Abstract] AND ADH1B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRIT1(40348990)-ADH1B(100240043), # samples:1
Anticipated loss of major functional domain due to fusion event.TRIT1-ADH1B 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.
TRIT1-ADH1B 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.
TRIT1-ADH1B 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.
TRIT1-ADH1B 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
TgeneADH1B

GO:0001523

retinoid metabolic process

15369820|16787387

TgeneADH1B

GO:0006069

ethanol oxidation

2398055



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/chr1:40348990/chr4:100240043)
- 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 TRIT1 (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 ADH1B (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)
ENST00000441669TRIT1chr140348990-ENST00000305046ADH1Bchr4100240043-416017401283427
ENST00000316891TRIT1chr140348990-ENST00000305046ADH1Bchr4100240043-4175189151298427
ENST00000372818TRIT1chr140348990-ENST00000305046ADH1Bchr4100240043-4175189151298427
ENST00000544981TRIT1chr140348990-ENST00000305046ADH1Bchr4100240043-4173187131296427

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
ENST00000441669ENST00000305046TRIT1chr140348990-ADH1Bchr4100240043-0.0001275990.9998723
ENST00000316891ENST00000305046TRIT1chr140348990-ADH1Bchr4100240043-0.0001295140.9998704
ENST00000372818ENST00000305046TRIT1chr140348990-ADH1Bchr4100240043-0.0001295140.9998704
ENST00000544981ENST00000305046TRIT1chr140348990-ADH1Bchr4100240043-0.0001280850.99987185

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 TRIT1-ADH1B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TRIT1chr140348990ADH1Bchr410024004317458RLGGEIVSADSMQVIKCKAAVLWEVK
TRIT1chr140348990ADH1Bchr410024004318758RLGGEIVSADSMQVIKCKAAVLWEVK
TRIT1chr140348990ADH1Bchr410024004318958RLGGEIVSADSMQVIKCKAAVLWEVK

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Potential FusionNeoAntigen Information of TRIT1-ADH1B 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.
TRIT1-ADH1B_40348990_100240043.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)
TRIT1-ADH1Bchr140348990chr4100240043189HLA-B08:09MQVIKCKAA0.91870.8251120
TRIT1-ADH1Bchr140348990chr4100240043189HLA-B57:01QVIKCKAAVLW0.99990.97781223
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C05:09SADSMQVI10.8878715
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C08:15SADSMQVI0.99990.9533715
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C08:04SADSMQVI0.97980.8927715
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C08:13SADSMQVI0.97980.8927715
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C08:03SADSMQVI0.81430.9459715
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C03:07VSADSMQVI0.99940.9491615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C15:06VSADSMQVI0.99920.8082615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C03:19VSADSMQVI0.99850.9621615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C03:08VSADSMQVI0.99850.7762615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C04:06VSADSMQVI0.99620.7642615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C12:04VSADSMQVI0.97860.9838615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C06:03VSADSMQVI0.97650.9805615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C12:12VSADSMQVI0.93610.83615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C08:13VSADSMQVI0.90960.9244615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C08:04VSADSMQVI0.90960.9244615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C08:03VSADSMQVI0.5870.9651615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C02:06VSADSMQVI0.54740.9038615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C04:03SADSMQVI10.771715
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C05:01SADSMQVI10.8878715
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C08:02SADSMQVI0.99990.9533715
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C08:01SADSMQVI0.81430.9459715
TRIT1-ADH1Bchr140348990chr4100240043189HLA-B07:13SADSMQVI0.53830.5108715
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C15:02VSADSMQVI0.99930.7475615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C15:05VSADSMQVI0.99920.8181615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C03:04VSADSMQVI0.99870.9736615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C03:03VSADSMQVI0.99870.9736615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C03:17VSADSMQVI0.99820.9468615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C03:06VSADSMQVI0.98930.9743615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C16:04VSADSMQVI0.96410.9348615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C12:03VSADSMQVI0.94370.95615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C16:02VSADSMQVI0.93840.9773615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C16:01VSADSMQVI0.79930.9484615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C08:01VSADSMQVI0.5870.9651615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-C17:01VSADSMQVI0.43330.7997615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-B07:13VSADSMQVI0.13270.5992615
TRIT1-ADH1Bchr140348990chr4100240043189HLA-B57:10QVIKCKAAVLW0.99990.97781223

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Potential FusionNeoAntigen Information of TRIT1-ADH1B 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.
TRIT1-ADH1B_40348990_100240043.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)
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-0478LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-0704LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-0901LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-0904LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-0905LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-0906LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-0907LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-0909LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1404LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1410LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1428LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1439LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1450LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1461LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1470LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1471LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1525LGGEIVSADSMQVIK116
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1525GGEIVSADSMQVIKC217
TRIT1-ADH1Bchr140348990chr4100240043189DRB1-1615LGGEIVSADSMQVIK116

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Fusion breakpoint peptide structures of TRIT1-ADH1B

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
10256VSADSMQVIKCKAATRIT1ADH1Bchr140348990chr4100240043189

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TRIT1-ADH1B

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-B14:023BVN10256VSADSMQVIKCKAA-7.9962-8.1096
HLA-B14:023BVN10256VSADSMQVIKCKAA-5.70842-6.74372
HLA-B52:013W3910256VSADSMQVIKCKAA-6.83737-6.95077
HLA-B52:013W3910256VSADSMQVIKCKAA-4.4836-5.5189
HLA-A11:014UQ210256VSADSMQVIKCKAA-10.0067-10.1201
HLA-A11:014UQ210256VSADSMQVIKCKAA-9.03915-10.0745
HLA-A24:025HGA10256VSADSMQVIKCKAA-6.56204-6.67544
HLA-A24:025HGA10256VSADSMQVIKCKAA-5.42271-6.45801
HLA-B44:053DX810256VSADSMQVIKCKAA-7.85648-8.89178
HLA-B44:053DX810256VSADSMQVIKCKAA-5.3978-5.5112
HLA-B35:011A1N10256VSADSMQVIKCKAA-6.27422-6.38762
HLA-B35:011A1N10256VSADSMQVIKCKAA-5.27424-6.30954
HLA-A02:016TDR10256VSADSMQVIKCKAA-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of TRIT1-ADH1B

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
TRIT1-ADH1Bchr140348990chr41002400431120MQVIKCKAAATGCAGGTAATCAAATGCAAAGCAGCT
TRIT1-ADH1Bchr140348990chr41002400431223QVIKCKAAVLWCAGGTAATCAAATGCAAAGCAGCTGTGCTATGG
TRIT1-ADH1Bchr140348990chr4100240043615VSADSMQVIGTCAGCGCTGACTCCATGCAGGTAATC
TRIT1-ADH1Bchr140348990chr4100240043715SADSMQVIAGCGCTGACTCCATGCAGGTAATC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TRIT1-ADH1Bchr140348990chr4100240043116LGGEIVSADSMQVIKCTCGGCGGTGAGATCGTCAGCGCTGACTCCATGCAGGTAATCAAA
TRIT1-ADH1Bchr140348990chr4100240043217GGEIVSADSMQVIKCGGCGGTGAGATCGTCAGCGCTGACTCCATGCAGGTAATCAAATGC

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Information of the samples that have these potential fusion neoantigens of TRIT1-ADH1B

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
LIHCTRIT1-ADH1Bchr140348990ENST00000316891chr4100240043ENST00000305046TCGA-PD-A5DF-01A

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Potential target of CAR-T therapy development for TRIT1-ADH1B

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 TRIT1-ADH1B

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 TRIT1-ADH1B

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