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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:RPAIN-FHIT

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RPAIN-FHIT
FusionPDB ID: 75691
FusionGDB2.0 ID: 75691
HgeneTgene
Gene symbol

RPAIN

FHIT

Gene ID

84268

2272

Gene nameRPA interacting proteinfragile histidine triad diadenosine triphosphatase
SynonymsHRIP|RIPAP3Aase|FRA3B
Cytomap

17p13.2

3p14.2

Type of geneprotein-codingprotein-coding
DescriptionRPA-interacting proteinRAP interaction proteinnuclear transporterbis(5'-adenosyl)-triphosphataseAP3A hydrolasediadenosine 5',5'''-P1,P3-triphosphate hydrolasedinucleosidetriphosphatase
Modification date2020032020200313
UniProtAcc.

P49789

Main function of 5'-partner protein: FUNCTION: Possesses dinucleoside triphosphate hydrolase activity (PubMed:12574506, PubMed:15182206, PubMed:8794732, PubMed:9323207, PubMed:9576908, PubMed:9543008). Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP (PubMed:12574506, PubMed:15182206, PubMed:8794732, PubMed:9323207, PubMed:9576908, PubMed:9543008). Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP (PubMed:8794732). Exhibits adenylylsulfatase activity, hydrolyzing adenosine 5'-phosphosulfate to yield AMP and sulfate (PubMed:18694747). Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (PubMed:18694747). Exhibits adenylylsulfate-ammonia adenylyltransferase, catalyzing the ammonolysis of adenosine 5'-phosphosulfate resulting in the formation of adenosine 5'-phosphoramidate (PubMed:26181368). Also catalyzes the ammonolysis of adenosine 5-phosphorofluoridate and diadenosine triphosphate (PubMed:26181368). Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5 (PubMed:18077326). Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways (PubMed:16407838). Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis (PubMed:15313915). Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity, it may in part come from the mitochondrial form, which sensitizes the low-affinity Ca(2+) transporters, enhancing mitochondrial calcium uptake (PubMed:12574506, PubMed:19622739). Functions as tumor suppressor (By similarity). {ECO:0000250|UniProtKB:O89106, ECO:0000269|PubMed:12574506, ECO:0000269|PubMed:15313915, ECO:0000269|PubMed:16407838, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18694747, ECO:0000269|PubMed:19622739, ECO:0000269|PubMed:26181368, ECO:0000269|PubMed:8794732, ECO:0000269|PubMed:9323207, ECO:0000269|PubMed:9543008}.
Ensembl transtripts involved in fusion geneENST idsENST00000327154, ENST00000381208, 
ENST00000381209, ENST00000405578, 
ENST00000536255, ENST00000574003, 
ENST00000341848, ENST00000466788, 
ENST00000468189, ENST00000476844, 
ENST00000492590, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 8 X 4=25627 X 20 X 11=5940
# samples 1032
** MAII scorelog2(10/256*10)=-1.35614381022528
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(32/5940*10)=-4.21431912080077
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RPAIN [Title/Abstract] AND FHIT [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RPAIN [Title/Abstract] AND FHIT [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RPAIN(5326149)-FHIT(59908140), # samples:4
Anticipated loss of major functional domain due to fusion event.RPAIN-FHIT 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.
RPAIN-FHIT 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.
RPAIN-FHIT 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.
RPAIN-FHIT 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.
RPAIN-FHIT seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
RPAIN-FHIT seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
RPAIN-FHIT seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
RPAIN-FHIT seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
HgeneRPAIN

GO:0006606

protein import into nucleus

16135809

TgeneFHIT

GO:0006163

purine nucleotide metabolic process

9323207



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/chr17:5326149/chr3:59908140)
- 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 RPAIN (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 FHIT (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)
ENST00000536255RPAINchr175326149+ENST00000476844FHITchr359999878-14888834681223251
ENST00000536255RPAINchr175326149+ENST00000492590FHITchr359999878-14998834681223251
ENST00000381208RPAINchr175326149+ENST00000476844FHITchr359999878-14888834681223251
ENST00000381208RPAINchr175326149+ENST00000492590FHITchr359999878-14998834681223251
ENST00000381209RPAINchr175326149+ENST00000476844FHITchr359999878-14888834681223251
ENST00000381209RPAINchr175326149+ENST00000492590FHITchr359999878-14998834681223251
ENST00000327154RPAINchr175326149+ENST00000476844FHITchr359999878-1241636221976251
ENST00000327154RPAINchr175326149+ENST00000492590FHITchr359999878-1252636221976251
ENST00000405578RPAINchr175326149+ENST00000476844FHITchr359999878-92932411664217
ENST00000405578RPAINchr175326149+ENST00000492590FHITchr359999878-94032411664217
ENST00000574003RPAINchr175326149+ENST00000476844FHITchr359999878-9273229662217
ENST00000574003RPAINchr175326149+ENST00000492590FHITchr359999878-9383229662217

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
ENST00000536255ENST00000476844RPAINchr175326149+FHITchr359999878-0.0037574310.99624264
ENST00000536255ENST00000492590RPAINchr175326149+FHITchr359999878-0.0034678830.9965321
ENST00000381208ENST00000476844RPAINchr175326149+FHITchr359999878-0.0037574310.99624264
ENST00000381208ENST00000492590RPAINchr175326149+FHITchr359999878-0.0034678830.9965321
ENST00000381209ENST00000476844RPAINchr175326149+FHITchr359999878-0.0037574310.99624264
ENST00000381209ENST00000492590RPAINchr175326149+FHITchr359999878-0.0034678830.9965321
ENST00000327154ENST00000476844RPAINchr175326149+FHITchr359999878-0.003368370.9966317
ENST00000327154ENST00000492590RPAINchr175326149+FHITchr359999878-0.0033650650.9966349
ENST00000405578ENST00000476844RPAINchr175326149+FHITchr359999878-0.0028999170.99710006
ENST00000405578ENST00000492590RPAINchr175326149+FHITchr359999878-0.0027998860.99720013
ENST00000574003ENST00000476844RPAINchr175326149+FHITchr359999878-0.0028556090.9971444
ENST00000574003ENST00000492590RPAINchr175326149+FHITchr359999878-0.0028845680.9971154

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 RPAIN-FHIT

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RPAINchr175326149FHITchr359999878322104AVLEEIQQELINQDVLVCPLRPVERF
RPAINchr175326149FHITchr359999878324104AVLEEIQQELINQDVLVCPLRPVERF
RPAINchr175326149FHITchr359999878636138AVLEEIQQELINQDVLVCPLRPVERF
RPAINchr175326149FHITchr359999878883138AVLEEIQQELINQDVLVCPLRPVERF

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Potential FusionNeoAntigen Information of RPAIN-FHIT 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.
RPAIN-FHIT_5326149_59999878.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)
RPAIN-FHITchr175326149chr359999878636HLA-B39:01NQDVLVCPL0.9630.97931120
RPAIN-FHITchr175326149chr359999878636HLA-B39:13QELINQDVL0.69960.8732716
RPAIN-FHITchr175326149chr359999878636HLA-B13:02IQQELINQDV0.57290.5369515
RPAIN-FHITchr175326149chr359999878636HLA-B39:09NQDVLVCPL0.95980.87061120
RPAIN-FHITchr175326149chr359999878636HLA-B39:05NQDVLVCPL0.93080.97671120
RPAIN-FHITchr175326149chr359999878636HLA-B39:08QELINQDVL0.59670.8313716
RPAIN-FHITchr175326149chr359999878636HLA-B40:04QELINQDVL0.99450.6255716
RPAIN-FHITchr175326149chr359999878636HLA-A68:02ELINQDVLV0.99440.7132817
RPAIN-FHITchr175326149chr359999878636HLA-A69:01ELINQDVLV0.9820.734817
RPAIN-FHITchr175326149chr359999878636HLA-B39:11NQDVLVCPL0.8930.87671120
RPAIN-FHITchr175326149chr359999878636HLA-B39:02QELINQDVL0.66750.8763716
RPAIN-FHITchr175326149chr359999878636HLA-B41:03QELINQDVL0.48370.7652716

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Potential FusionNeoAntigen Information of RPAIN-FHIT 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 RPAIN-FHIT

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
7492QQELINQDVLVCPLRPAINFHITchr175326149chr359999878636

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RPAIN-FHIT

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-B14:023BVN7492QQELINQDVLVCPL-6.00367-7.03897
HLA-B14:023BVN7492QQELINQDVLVCPL-5.39279-5.50619
HLA-B52:013W397492QQELINQDVLVCPL-6.37513-6.48853
HLA-B52:013W397492QQELINQDVLVCPL-5.71942-6.75472
HLA-A11:014UQ27492QQELINQDVLVCPL-11.5708-11.6842
HLA-A11:014UQ27492QQELINQDVLVCPL-8.11091-9.14621
HLA-A24:025HGA7492QQELINQDVLVCPL-6.75661-6.87001
HLA-A24:025HGA7492QQELINQDVLVCPL-5.30147-6.33677
HLA-B27:056PYJ7492QQELINQDVLVCPL-4.27108-5.30638
HLA-B44:053DX87492QQELINQDVLVCPL-6.47731-6.59071
HLA-B44:053DX87492QQELINQDVLVCPL-3.23433-4.26963

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Vaccine Design for the FusionNeoAntigens of RPAIN-FHIT

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
RPAIN-FHITchr175326149chr3599998781120NQDVLVCPLACCAAGATGTCCTTGTGTGCCCGCTGC
RPAIN-FHITchr175326149chr359999878515IQQELINQDVTTCAACAGGAGCTGATCAACCAAGATGTCC
RPAIN-FHITchr175326149chr359999878716QELINQDVLAGGAGCTGATCAACCAAGATGTCCTTG
RPAIN-FHITchr175326149chr359999878817ELINQDVLVAGCTGATCAACCAAGATGTCCTTGTGT

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 RPAIN-FHIT

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
BRCARPAIN-FHITchr175326149ENST00000327154chr359999878ENST00000476844TCGA-A7-A0CJ-01A

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Potential target of CAR-T therapy development for RPAIN-FHIT

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 RPAIN-FHIT

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 RPAIN-FHIT

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
TgeneFHITC0024121Lung Neoplasms2CTD_human
TgeneFHITC0025500Mesothelioma2CTD_human
TgeneFHITC0242379Malignant neoplasm of lung2CTD_human
TgeneFHITC0007097Carcinoma1CTD_human
TgeneFHITC0007131Non-Small Cell Lung Carcinoma1CTD_human
TgeneFHITC0013146Drug abuse1CTD_human
TgeneFHITC0013170Drug habituation1CTD_human
TgeneFHITC0013222Drug Use Disorders1CTD_human
TgeneFHITC0023903Liver neoplasms1CTD_human
TgeneFHITC0024623Malignant neoplasm of stomach1CTD_human
TgeneFHITC0029231Organic Mental Disorders, Substance-Induced1CTD_human
TgeneFHITC0033578Prostatic Neoplasms1CTD_human
TgeneFHITC0038356Stomach Neoplasms1CTD_human
TgeneFHITC0038580Substance Dependence1CTD_human
TgeneFHITC0038586Substance Use Disorders1CTD_human
TgeneFHITC0042076Urologic Neoplasms1CTD_human
TgeneFHITC0205696Anaplastic carcinoma1CTD_human
TgeneFHITC0205697Carcinoma, Spindle-Cell1CTD_human
TgeneFHITC0205698Undifferentiated carcinoma1CTD_human
TgeneFHITC0205699Carcinomatosis1CTD_human
TgeneFHITC0236733Amphetamine-Related Disorders1CTD_human
TgeneFHITC0236804Amphetamine Addiction1CTD_human
TgeneFHITC0236807Amphetamine Abuse1CTD_human
TgeneFHITC0236969Substance-Related Disorders1CTD_human
TgeneFHITC0345904Malignant neoplasm of liver1CTD_human
TgeneFHITC0376358Malignant neoplasm of prostate1CTD_human
TgeneFHITC0740858Substance abuse problem1CTD_human
TgeneFHITC0751571Cancer of Urinary Tract1CTD_human
TgeneFHITC1510472Drug Dependence1CTD_human
TgeneFHITC1708349Hereditary Diffuse Gastric Cancer1CTD_human
TgeneFHITC4316881Prescription Drug Abuse1CTD_human