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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:INPP4B-NAA15

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: INPP4B-NAA15
FusionPDB ID: 39791
FusionGDB2.0 ID: 39791
HgeneTgene
Gene symbol

INPP4B

NAA15

Gene ID

8821

80155

Gene nameinositol polyphosphate-4-phosphatase type II BN-alpha-acetyltransferase 15, NatA auxiliary subunit
Synonyms-Ga19|MRD50|NARG1|NAT1P|NATH|TBDN|TBDN100
Cytomap

4q31.21

4q31.1

Type of geneprotein-codingprotein-coding
Descriptioninositol polyphosphate 4-phosphatase type IIinositol polyphosphate 4-phosphatase II; 4-phosphatase IIinositol polyphosphate-4-phosphatase, type II, 105kDatype II inositol 3,4-bisphosphate 4-phosphataseN-alpha-acetyltransferase 15, NatA auxiliary subunitN-terminal acetyltransferaseNMDA receptor regulated 1NMDA receptor-regulated protein 1gastric cancer antigen Ga19protein tubedown-1transcriptional coactivator tubedown-100tubedown-1
Modification date2020031320200313
UniProtAcc

O15327

Main function of 5'-partner protein: FUNCTION: Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and inositol 3,4-trisphosphate (PubMed:24070612, PubMed:24591580). Plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3,4-bisphosphate in membrane ruffles (PubMed:24591580). The lipid phosphatase activity is critical for tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:19647222, PubMed:24070612). {ECO:0000269|PubMed:19647222, ECO:0000269|PubMed:24070612, ECO:0000269|PubMed:24591580}.

Q9BXJ9

Main function of 5'-partner protein: FUNCTION: Auxillary subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity. The NAT activity may be important for vascular, hematopoietic and neuronal growth and development. Required to control retinal neovascularization in adult ocular endothelial cells. In complex with XRCC6 and XRCC5 (Ku80), up-regulates transcription from the osteocalcin promoter. {ECO:0000269|PubMed:11687548, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:15496142}.
Ensembl transtripts involved in fusion geneENST idsENST00000262992, ENST00000308502, 
ENST00000506217, ENST00000508116, 
ENST00000509777, ENST00000513000, 
ENST00000507861, ENST00000508084, 
ENST00000480277, ENST00000515576, 
ENST00000296543, ENST00000398947, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 12 X 5=78014 X 11 X 8=1232
# samples 1415
** MAII scorelog2(14/780*10)=-2.47804729680464
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/1232*10)=-3.03796785019902
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: INPP4B [Title/Abstract] AND NAA15 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: INPP4B [Title/Abstract] AND NAA15 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)INPP4B(143324091)-NAA15(140255328), # samples:1
Anticipated loss of major functional domain due to fusion event.INPP4B-NAA15 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.
INPP4B-NAA15 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.
INPP4B-NAA15 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.
INPP4B-NAA15 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.
INPP4B-NAA15 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
INPP4B-NAA15 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
INPP4B-NAA15 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
INPP4B-NAA15 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
INPP4B-NAA15 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
TgeneNAA15

GO:0006474

N-terminal protein amino acid acetylation

15496142

TgeneNAA15

GO:0045893

positive regulation of transcription, DNA-templated

12145306



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/chr4:143324091/chr4:140255328)
- 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 INPP4B (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 NAA15 (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)
ENST00000513000INPP4Bchr4143324091-ENST00000296543NAA15chr4140255328+66518064283352974
ENST00000513000INPP4Bchr4143324091-ENST00000398947NAA15chr4140255328+66348064283349973
ENST00000509777INPP4Bchr4143324091-ENST00000296543NAA15chr4140255328+65627173393263974
ENST00000509777INPP4Bchr4143324091-ENST00000398947NAA15chr4140255328+65457173393260973
ENST00000308502INPP4Bchr4143324091-ENST00000296543NAA15chr4140255328+63374921143038974
ENST00000308502INPP4Bchr4143324091-ENST00000398947NAA15chr4140255328+63204921143035973
ENST00000506217INPP4Bchr4143324091-ENST00000296543NAA15chr4140255328+621737202918972
ENST00000506217INPP4Bchr4143324091-ENST00000398947NAA15chr4140255328+620037202915971

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
ENST00000513000ENST00000296543INPP4Bchr4143324091-NAA15chr4140255328+0.0002348190.9997652
ENST00000513000ENST00000398947INPP4Bchr4143324091-NAA15chr4140255328+0.000211950.9997881
ENST00000509777ENST00000296543INPP4Bchr4143324091-NAA15chr4140255328+0.0002030780.9997969
ENST00000509777ENST00000398947INPP4Bchr4143324091-NAA15chr4140255328+0.0001833850.9998166
ENST00000308502ENST00000296543INPP4Bchr4143324091-NAA15chr4140255328+0.0001831240.99981695
ENST00000308502ENST00000398947INPP4Bchr4143324091-NAA15chr4140255328+0.0001669990.999833
ENST00000506217ENST00000296543INPP4Bchr4143324091-NAA15chr4140255328+0.0001835080.9998165
ENST00000506217ENST00000398947INPP4Bchr4143324091-NAA15chr4140255328+0.0001678030.99983215

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 INPP4B-NAA15

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
INPP4Bchr4143324091NAA15chr4140255328372124LTVYDVKDKSHDTRCYEHKQYRNGLK
INPP4Bchr4143324091NAA15chr4140255328492126LTVYDVKDKSHDTRCYEHKQYRNGLK
INPP4Bchr4143324091NAA15chr4140255328717126LTVYDVKDKSHDTRCYEHKQYRNGLK
INPP4Bchr4143324091NAA15chr4140255328806126LTVYDVKDKSHDTRCYEHKQYRNGLK

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Potential FusionNeoAntigen Information of INPP4B-NAA15 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.
INPP4B-NAA15_143324091_140255328.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)
INPP4B-NAA15chr4143324091chr4140255328492HLA-B27:02TRCYEHKQY0.99680.57411221
INPP4B-NAA15chr4143324091chr4140255328492HLA-B15:18TRCYEHKQY0.2910.50751221
INPP4B-NAA15chr4143324091chr4140255328492HLA-A66:01DTRCYEHKQYR0.98730.53321122
INPP4B-NAA15chr4143324091chr4140255328492HLA-C07:95TRCYEHKQY0.98030.55271221
INPP4B-NAA15chr4143324091chr4140255328492HLA-C07:27TRCYEHKQY0.96070.85771221
INPP4B-NAA15chr4143324091chr4140255328492HLA-C07:19TRCYEHKQY0.81360.59291221
INPP4B-NAA15chr4143324091chr4140255328492HLA-C07:67TRCYEHKQY0.7930.81241221
INPP4B-NAA15chr4143324091chr4140255328492HLA-C07:80TRCYEHKQY0.7930.81241221
INPP4B-NAA15chr4143324091chr4140255328492HLA-C07:46TRCYEHKQY0.78990.73291221
INPP4B-NAA15chr4143324091chr4140255328492HLA-C12:16TRCYEHKQY0.0230.81381221
INPP4B-NAA15chr4143324091chr4140255328492HLA-C07:01TRCYEHKQY0.98610.56261221
INPP4B-NAA15chr4143324091chr4140255328492HLA-C07:02TRCYEHKQY0.7930.81241221
INPP4B-NAA15chr4143324091chr4140255328492HLA-A30:01KSHDTRCYEHK0.99890.7781819

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Potential FusionNeoAntigen Information of INPP4B-NAA15 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.
INPP4B-NAA15_143324091_140255328.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)
INPP4B-NAA15chr4143324091chr4140255328492DRB1-1338LTVYDVKDKSHDTRC015
INPP4B-NAA15chr4143324091chr4140255328492DRB1-1365LTVYDVKDKSHDTRC015

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Fusion breakpoint peptide structures of INPP4B-NAA15

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
4153KDKSHDTRCYEHKQINPP4BNAA15chr4143324091chr4140255328492

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of INPP4B-NAA15

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-B14:023BVN4153KDKSHDTRCYEHKQ-7.9962-8.1096
HLA-B14:023BVN4153KDKSHDTRCYEHKQ-5.70842-6.74372
HLA-B52:013W394153KDKSHDTRCYEHKQ-6.83737-6.95077
HLA-B52:013W394153KDKSHDTRCYEHKQ-4.4836-5.5189
HLA-A11:014UQ24153KDKSHDTRCYEHKQ-10.0067-10.1201
HLA-A11:014UQ24153KDKSHDTRCYEHKQ-9.03915-10.0745
HLA-A24:025HGA4153KDKSHDTRCYEHKQ-6.56204-6.67544
HLA-A24:025HGA4153KDKSHDTRCYEHKQ-5.42271-6.45801
HLA-B44:053DX84153KDKSHDTRCYEHKQ-7.85648-8.89178
HLA-B44:053DX84153KDKSHDTRCYEHKQ-5.3978-5.5112
HLA-A02:016TDR4153KDKSHDTRCYEHKQ-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of INPP4B-NAA15

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
INPP4B-NAA15chr4143324091chr41402553281122DTRCYEHKQYRGACACCAGGTGTTATGAACATAAACAGTATAGA
INPP4B-NAA15chr4143324091chr41402553281221TRCYEHKQYACCAGGTGTTATGAACATAAACAGTAT
INPP4B-NAA15chr4143324091chr4140255328819KSHDTRCYEHKAAGTCTCATGACACCAGGTGTTATGAACATAAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
INPP4B-NAA15chr4143324091chr4140255328015LTVYDVKDKSHDTRCCTAACAGTCTATGATGTCAAGGATAAGTCTCATGACACCAGGTGT

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Information of the samples that have these potential fusion neoantigens of INPP4B-NAA15

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
LUSCINPP4B-NAA15chr4143324091ENST00000308502chr4140255328ENST00000296543TCGA-NC-A5HT-01A

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Potential target of CAR-T therapy development for INPP4B-NAA15

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 INPP4B-NAA15

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 INPP4B-NAA15

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