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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:API5-GANC

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: API5-GANC
FusionPDB ID: 5422
FusionGDB2.0 ID: 5422
HgeneTgene
Gene symbol

API5

GANC

Gene ID

8539

2595

Gene nameapoptosis inhibitor 5glucosidase alpha, neutral C
SynonymsAAC-11|AAC11-
Cytomap

11p12

15q15.1

Type of geneprotein-codingprotein-coding
Descriptionapoptosis inhibitor 5FIFantiapoptosis clone 11 proteincell migration-inducing gene 8 proteinfibroblast growth factor 2-interacting factor 2migration-inducing protein MIG8neutral alpha-glucosidase C
Modification date2020031320200313
UniProtAcc

Q9BZZ5

Main function of 5'-partner protein: FUNCTION: Antiapoptotic factor that may have a role in protein assembly. Negatively regulates ACIN1. By binding to ACIN1, it suppresses ACIN1 cleavage from CASP3 and ACIN1-mediated DNA fragmentation. Also known to efficiently suppress E2F1-induced apoptosis. Its depletion enhances the cytotoxic action of the chemotherapeutic drugs. {ECO:0000269|PubMed:10780674, ECO:0000269|PubMed:17112319, ECO:0000269|PubMed:19387494}.

Q8TET4

Main function of 5'-partner protein: FUNCTION: Has alpha-glucosidase activity. {ECO:0000269|PubMed:12370436}.
Ensembl transtripts involved in fusion geneENST idsENST00000378852, ENST00000420461, 
ENST00000455725, ENST00000531273, 
ENST00000534600, ENST00000529334, 
ENST00000534695, 
ENST00000440615, 
ENST00000318010, ENST00000566442, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 5 X 5=1757 X 6 X 3=126
# samples 76
** MAII scorelog2(7/175*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/126*10)=-1.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: API5 [Title/Abstract] AND GANC [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: API5 [Title/Abstract] AND GANC [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)API5(43343686)-GANC(42598744), # samples:3
Anticipated loss of major functional domain due to fusion event.API5-GANC 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.
API5-GANC 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


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/chr11:43343686/chr15:42598744)
- 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 API5 (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 GANC (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)
ENST00000455725API5chr1143343686+ENST00000566442GANCchr1542598744+20087552451270341
ENST00000455725API5chr1143343686+ENST00000318010GANCchr1542598744+44697552452941898
ENST00000531273API5chr1143343686+ENST00000566442GANCchr1542598744+19356821211197358
ENST00000531273API5chr1143343686+ENST00000318010GANCchr1542598744+43966821212868915
ENST00000420461API5chr1143343686+ENST00000566442GANCchr1542598744+17645111121026304
ENST00000420461API5chr1143343686+ENST00000318010GANCchr1542598744+42255111122697861
ENST00000378852API5chr1143343686+ENST00000566442GANCchr1542598744+19216681071183358
ENST00000378852API5chr1143343686+ENST00000318010GANCchr1542598744+43826681072854915
ENST00000534600API5chr1143343686+ENST00000566442GANCchr1542598744+1828575141090358
ENST00000534600API5chr1143343686+ENST00000318010GANCchr1542598744+4289575142761915

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
ENST00000455725ENST00000566442API5chr1143343686+GANCchr1542598744+0.0021842150.9978157
ENST00000455725ENST00000318010API5chr1143343686+GANCchr1542598744+0.0012277970.9987722
ENST00000531273ENST00000566442API5chr1143343686+GANCchr1542598744+0.000669030.999331
ENST00000531273ENST00000318010API5chr1143343686+GANCchr1542598744+0.0008313660.99916863
ENST00000420461ENST00000566442API5chr1143343686+GANCchr1542598744+0.0007221240.9992779
ENST00000420461ENST00000318010API5chr1143343686+GANCchr1542598744+0.0010109290.99898905
ENST00000378852ENST00000566442API5chr1143343686+GANCchr1542598744+0.0006668650.9993331
ENST00000378852ENST00000318010API5chr1143343686+GANCchr1542598744+0.0008408110.9991592
ENST00000534600ENST00000566442API5chr1143343686+GANCchr1542598744+0.0006686810.99933136
ENST00000534600ENST00000318010API5chr1143343686+GANCchr1542598744+0.0008618250.9991381

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 API5-GANC

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
API5chr1143343686GANCchr1542598744511133KEVEELILTESKKENQEDLGLWEEKF
API5chr1143343686GANCchr1542598744575187KEVEELILTESKKENQEDLGLWEEKF
API5chr1143343686GANCchr1542598744668187KEVEELILTESKKENQEDLGLWEEKF
API5chr1143343686GANCchr1542598744682187KEVEELILTESKKENQEDLGLWEEKF
API5chr1143343686GANCchr1542598744755170KEVEELILTESKKENQEDLGLWEEKF

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Potential FusionNeoAntigen Information of API5-GANC 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.
API5-GANC_43343686_42598744.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)
API5-GANCchr1143343686chr1542598744668HLA-B39:13KENQEDLGL0.35190.95111221
API5-GANCchr1143343686chr1542598744668HLA-B44:03KENQEDLGLW0.99870.98211222
API5-GANCchr1143343686chr1542598744668HLA-B39:08KENQEDLGL0.4210.73511221
API5-GANCchr1143343686chr1542598744668HLA-B44:10KENQEDLGLW0.86130.64191222
API5-GANCchr1143343686chr1542598744668HLA-B40:04KENQEDLGL0.99490.62051221
API5-GANCchr1143343686chr1542598744668HLA-B41:03KENQEDLGL0.48330.52661221
API5-GANCchr1143343686chr1542598744668HLA-B39:02KENQEDLGL0.30450.95251221
API5-GANCchr1143343686chr1542598744668HLA-B44:26KENQEDLGLW0.99870.98211222
API5-GANCchr1143343686chr1542598744668HLA-B44:07KENQEDLGLW0.99870.98211222
API5-GANCchr1143343686chr1542598744668HLA-B44:13KENQEDLGLW0.99870.98211222

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Potential FusionNeoAntigen Information of API5-GANC 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.
API5-GANC_43343686_42598744.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)
API5-GANCchr1143343686chr1542598744668DRB1-1183EELILTESKKENQED318

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Fusion breakpoint peptide structures of API5-GANC

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
3820ILTESKKENQEDLGAPI5GANCchr1143343686chr1542598744668

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of API5-GANC

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-B14:023BVN3820ILTESKKENQEDLG-7.9962-8.1096
HLA-B14:023BVN3820ILTESKKENQEDLG-5.70842-6.74372
HLA-B52:013W393820ILTESKKENQEDLG-6.83737-6.95077
HLA-B52:013W393820ILTESKKENQEDLG-4.4836-5.5189
HLA-A11:014UQ23820ILTESKKENQEDLG-10.0067-10.1201
HLA-A11:014UQ23820ILTESKKENQEDLG-9.03915-10.0745
HLA-A24:025HGA3820ILTESKKENQEDLG-6.56204-6.67544
HLA-A24:025HGA3820ILTESKKENQEDLG-5.42271-6.45801
HLA-B44:053DX83820ILTESKKENQEDLG-7.85648-8.89178
HLA-B44:053DX83820ILTESKKENQEDLG-5.3978-5.5112
HLA-A02:016TDR3820ILTESKKENQEDLG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of API5-GANC

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
API5-GANCchr1143343686chr15425987441221KENQEDLGLAAGGAAAATCAAGAAGATCTGGGCCTG
API5-GANCchr1143343686chr15425987441222KENQEDLGLWAAGGAAAATCAAGAAGATCTGGGCCTGTGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
API5-GANCchr1143343686chr1542598744318EELILTESKKENQEDGAAGAGCTTATACTAACTGAATCCAAAAAGGAAAATCAAGAAGAT

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Information of the samples that have these potential fusion neoantigens of API5-GANC

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
SKCMAPI5-GANCchr1143343686ENST00000378852chr1542598744ENST00000318010TCGA-FS-A4FB-06A

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Potential target of CAR-T therapy development for API5-GANC

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 API5-GANC

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 API5-GANC

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