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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:ATG7-FHIT

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ATG7-FHIT
FusionPDB ID: 7612
FusionGDB2.0 ID: 7612
HgeneTgene
Gene symbol

ATG7

FHIT

Gene ID

10533

2272

Gene nameautophagy related 7fragile histidine triad diadenosine triphosphatase
SynonymsAPG7-LIKE|APG7L|GSA7AP3Aase|FRA3B
Cytomap

3p25.3

3p14.2

Type of geneprotein-codingprotein-coding
Descriptionubiquitin-like modifier-activating enzyme ATG7APG7 autophagy 7-likeATG12-activating enzyme E1 ATG7hAGP7ubiquitin-activating enzyme E1-like proteinbis(5'-adenosyl)-triphosphataseAP3A hydrolasediadenosine 5',5'''-P1,P3-triphosphate hydrolasedinucleosidetriphosphatase
Modification date2020032920200313
UniProtAcc

O95352

Main function of 5'-partner protein: FUNCTION: E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress. Plays also a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration, the maintenance of hematopoietic stem cells, the formation of Paneth cell granules, as well as in adipose differentiation. Plays a role in regulating the liver clock and glucose metabolism by mediating the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q9D906, ECO:0000269|PubMed:11096062, ECO:0000269|PubMed:16303767, ECO:0000269|PubMed:22170151}.

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 idsENST00000354449, ENST00000354956, 
ENST00000446450, ENST00000469654, 
ENST00000341848, ENST00000466788, 
ENST00000468189, ENST00000476844, 
ENST00000492590, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 16 X 9=216027 X 20 X 11=5940
# samples 2032
** MAII scorelog2(20/2160*10)=-3.43295940727611
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: ATG7 [Title/Abstract] AND FHIT [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ATG7 [Title/Abstract] AND FHIT [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ATG7(11406208)-FHIT(59908140), # samples:1
Anticipated loss of major functional domain due to fusion event.ATG7-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.
ATG7-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.
ATG7-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.
ATG7-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.
* 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
HgeneATG7

GO:0006497

protein lipidation

12890687

HgeneATG7

GO:0009267

cellular response to starvation

20543840

HgeneATG7

GO:0031401

positive regulation of protein modification process

12890687

HgeneATG7

GO:0071455

cellular response to hyperoxia

20543840

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/chr3:11406208/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 ATG7 (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)
ENST00000446450ATG7chr311406208-ENST00000476844FHITchr359908140-22121783251947640
ENST00000446450ATG7chr311406208-ENST00000492590FHITchr359908140-22231783251947640
ENST00000354956ATG7chr311406208-ENST00000476844FHITchr359908140-23291900252064679
ENST00000354956ATG7chr311406208-ENST00000492590FHITchr359908140-23401900252064679
ENST00000354449ATG7chr311406208-ENST00000476844FHITchr359908140-23291900252064679
ENST00000354449ATG7chr311406208-ENST00000492590FHITchr359908140-23401900252064679

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
ENST00000446450ENST00000476844ATG7chr311406208-FHITchr359908140-0.0041853190.9958146
ENST00000446450ENST00000492590ATG7chr311406208-FHITchr359908140-0.0041705040.9958295
ENST00000354956ENST00000476844ATG7chr311406208-FHITchr359908140-0.0063964860.9936035
ENST00000354956ENST00000492590ATG7chr311406208-FHITchr359908140-0.0064107390.9935893
ENST00000354449ENST00000476844ATG7chr311406208-FHITchr359908140-0.0063964860.9936035
ENST00000354449ENST00000492590ATG7chr311406208-FHITchr359908140-0.0064107390.9935893

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 ATG7-FHIT

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ATG7chr311406208FHITchr3599081401783581SDDRMNEPPTSLGLVPHQHVHVHVLP
ATG7chr311406208FHITchr3599081401900620SDDRMNEPPTSLGLVPHQHVHVHVLP

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Potential FusionNeoAntigen Information of ATG7-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.
ATG7-FHIT_11406208_59908140.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)
ATG7-FHITchr311406208chr3599081401900HLA-B18:01NEPPTSLGL0.49480.7201514
ATG7-FHITchr311406208chr3599081401900HLA-B15:37NEPPTSLGL0.40650.5107514
ATG7-FHITchr311406208chr3599081401900HLA-B39:13NEPPTSLGL0.34880.85514
ATG7-FHITchr311406208chr3599081401900HLA-A02:13GLVPHQHVHV0.99330.68111222
ATG7-FHITchr311406208chr3599081401900HLA-A02:27GLVPHQHVHV0.99240.51841222
ATG7-FHITchr311406208chr3599081401900HLA-A02:38GLVPHQHVHV0.98610.64911222
ATG7-FHITchr311406208chr3599081401900HLA-A02:13RMNEPPTSLGL0.99150.7588314
ATG7-FHITchr311406208chr3599081401900HLA-A02:27RMNEPPTSLGL0.98740.661314
ATG7-FHITchr311406208chr3599081401900HLA-A02:11RMNEPPTSLGL0.9660.6558314
ATG7-FHITchr311406208chr3599081401900HLA-A02:20RMNEPPTSLGL0.91490.606314
ATG7-FHITchr311406208chr3599081401900HLA-B13:01RMNEPPTSLGL0.80720.8105314
ATG7-FHITchr311406208chr3599081401900HLA-B15:04GLVPHQHVH0.61450.87751221
ATG7-FHITchr311406208chr3599081401900HLA-B39:08NEPPTSLGL0.31070.7182514
ATG7-FHITchr311406208chr3599081401900HLA-B39:05NEPPTSLGL0.3060.7918514
ATG7-FHITchr311406208chr3599081401900HLA-B18:05NEPPTSLGL0.49480.7201514
ATG7-FHITchr311406208chr3599081401900HLA-B18:08NEPPTSLGL0.48010.7311514
ATG7-FHITchr311406208chr3599081401900HLA-B18:06NEPPTSLGL0.43310.7289514
ATG7-FHITchr311406208chr3599081401900HLA-B18:03NEPPTSLGL0.41710.7089514
ATG7-FHITchr311406208chr3599081401900HLA-B18:11NEPPTSLGL0.37470.7245514
ATG7-FHITchr311406208chr3599081401900HLA-B39:31NEPPTSLGL0.35820.8117514
ATG7-FHITchr311406208chr3599081401900HLA-B39:02NEPPTSLGL0.34560.8469514
ATG7-FHITchr311406208chr3599081401900HLA-B39:11NEPPTSLGL0.2790.6674514
ATG7-FHITchr311406208chr3599081401900HLA-A02:03GLVPHQHVHV0.99690.60951222
ATG7-FHITchr311406208chr3599081401900HLA-C01:03RMNEPPTSLGL0.99990.8913314
ATG7-FHITchr311406208chr3599081401900HLA-B15:73RMNEPPTSLGL0.99960.8579314
ATG7-FHITchr311406208chr3599081401900HLA-B15:30RMNEPPTSLGL0.99840.8544314
ATG7-FHITchr311406208chr3599081401900HLA-A02:03RMNEPPTSLGL0.99670.669314
ATG7-FHITchr311406208chr3599081401900HLA-A32:01RMNEPPTSLGL0.99490.9717314
ATG7-FHITchr311406208chr3599081401900HLA-C01:02RMNEPPTSLGL0.99320.9432314

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Potential FusionNeoAntigen Information of ATG7-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 ATG7-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
2019EPPTSLGLVPHQHVATG7FHITchr311406208chr3599081401900

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ATG7-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-B14:023BVN2019EPPTSLGLVPHQHV-4.62424-5.65954
HLA-B14:023BVN2019EPPTSLGLVPHQHV-4.1114-4.2248
HLA-B52:013W392019EPPTSLGLVPHQHV-6.8001-6.9135
HLA-B52:013W392019EPPTSLGLVPHQHV-6.46104-7.49634
HLA-A24:025HGA2019EPPTSLGLVPHQHV-9.1447-9.2581
HLA-A24:025HGA2019EPPTSLGLVPHQHV-6.01279-7.04809
HLA-B44:053DX82019EPPTSLGLVPHQHV-5.02862-5.14202
HLA-B44:053DX82019EPPTSLGLVPHQHV-4.60714-5.64244

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Vaccine Design for the FusionNeoAntigens of ATG7-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
ATG7-FHITchr311406208chr3599081401221GLVPHQHVHCAGCACGTTCACGTCCATGTTCTTCCC
ATG7-FHITchr311406208chr3599081401222GLVPHQHVHVCAGCACGTTCACGTCCATGTTCTTCCCAGG
ATG7-FHITchr311406208chr359908140314RMNEPPTSLGLCCAACCTCTCTTGGGCTTGTGCCTCACCAGCAC
ATG7-FHITchr311406208chr359908140514NEPPTSLGLTCTCTTGGGCTTGTGCCTCACCAGCAC

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 ATG7-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
BLCAATG7-FHITchr311406208ENST00000354449chr359908140ENST00000476844TCGA-XF-A9SK-01A

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Potential target of CAR-T therapy development for ATG7-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 ATG7-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 ATG7-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