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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:ACTG1-CXCR5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ACTG1-CXCR5
FusionPDB ID: 1670
FusionGDB2.0 ID: 1670
HgeneTgene
Gene symbol

ACTG1

CXCR5

Gene ID

71

643

Gene nameactin gamma 1C-X-C motif chemokine receptor 5
SynonymsACT|ACTG|DFNA20|DFNA26|HEL-176BLR1|CD185|MDR15
Cytomap

17q25.3

11q23.3

Type of geneprotein-codingprotein-coding
Descriptionactin, cytoplasmic 2cytoskeletal gamma-actinepididymis luminal protein 176C-X-C chemokine receptor type 5Burkitt lymphoma receptor 1, GTP binding protein (chemokine (C-X-C motif) receptor 5)Burkitt lymphoma receptor 1, GTP-binding proteinCXC-R5CXCR-5MDR-15chemokine (C-X-C motif) receptor 5monocyte-derived receptor 15
Modification date2020032720200313
UniProtAcc

P63261

Main function of 5'-partner protein: FUNCTION: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. {ECO:0000305|PubMed:29581253}.

P32302

Main function of 5'-partner protein: FUNCTION: Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC). Involved in B-cell migration into B-cell follicles of spleen and Peyer patches but not into those of mesenteric or peripheral lymph nodes. May have a regulatory function in Burkitt lymphoma (BL) lymphomagenesis and/or B-cell differentiation.
Ensembl transtripts involved in fusion geneENST idsENST00000331925, ENST00000573283, 
ENST00000575087, ENST00000575842, 
ENST00000292174, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score51 X 36 X 13=2386812 X 4 X 8=384
# samples 5812
** MAII scorelog2(58/23868*10)=-5.36288097153997
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/384*10)=-1.67807190511264
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ACTG1 [Title/Abstract] AND CXCR5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ACTG1 [Title/Abstract] AND CXCR5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ACTG1(79476999)-CXCR5(118754475), # samples:1
Anticipated loss of major functional domain due to fusion event.
* 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/chr17:79476999/chr11:118754475)
- 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 ACTG1 (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 CXCR5 (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)
ENST00000331925ACTG1chr1779476999-ENST00000292174CXCR5chr11118754475+642519941351274379

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
ENST00000331925ENST00000292174ACTG1chr1779476999-CXCR5chr11118754475+0.0024746270.9975254

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 ACTG1-CXCR5

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

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Potential FusionNeoAntigen Information of ACTG1-CXCR5 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.

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)

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Potential FusionNeoAntigen Information of ACTG1-CXCR5 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 ACTG1-CXCR5

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ACTG1-CXCR5

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

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Vaccine Design for the FusionNeoAntigens of ACTG1-CXCR5

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

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 ACTG1-CXCR5

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

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Potential target of CAR-T therapy development for ACTG1-CXCR5

check button Predicted 3D structure. We used RoseTTAFold.
11_ACTG1-CXCR5_bf3a9_pred.pdb


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
TgeneCXCR5chr17:79476999chr11:118754475ENST00000292174-12125_1450373.0TransmembraneHelical%3B Name%3D3
TgeneCXCR5chr17:79476999chr11:118754475ENST00000292174-12168_1880373.0TransmembraneHelical%3B Name%3D4
TgeneCXCR5chr17:79476999chr11:118754475ENST00000292174-12220_2400373.0TransmembraneHelical%3B Name%3D5
TgeneCXCR5chr17:79476999chr11:118754475ENST00000292174-12260_2800373.0TransmembraneHelical%3B Name%3D6
TgeneCXCR5chr17:79476999chr11:118754475ENST00000292174-12305_3250373.0TransmembraneHelical%3B Name%3D7
TgeneCXCR5chr17:79476999chr11:118754475ENST00000292174-1256_760373.0TransmembraneHelical%3B Name%3D1
TgeneCXCR5chr17:79476999chr11:118754475ENST00000292174-1289_1090373.0TransmembraneHelical%3B Name%3D2

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
ACTG1chr1779476999ENST00000331925CXCR5chr11118754475ENST00000292174

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Related Drugs to ACTG1-CXCR5

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 ACTG1-CXCR5

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
HgeneACTG1C3711374Nonsyndromic Deafness18CLINGEN
HgeneACTG1C1858172Deafness, Autosomal Dominant 208CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneACTG1C3281235BARAITSER-WINTER SYNDROME 24CLINGEN;CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneACTG1C0001787Osteoporosis, Age-Related1CTD_human
HgeneACTG1C0005745Blepharoptosis1GENOMICS_ENGLAND
HgeneACTG1C0007097Carcinoma1CTD_human
HgeneACTG1C0007621Neoplastic Cell Transformation1CTD_human
HgeneACTG1C0009363Congenital ocular coloboma (disorder)1CTD_human
HgeneACTG1C0014544Epilepsy1GENOMICS_ENGLAND
HgeneACTG1C0024433Macrostomia1GENOMICS_ENGLAND
HgeneACTG1C0024667Animal Mammary Neoplasms1CTD_human
HgeneACTG1C0024668Mammary Neoplasms, Experimental1CTD_human
HgeneACTG1C0029456Osteoporosis1CTD_human
HgeneACTG1C0029459Osteoporosis, Senile1CTD_human
HgeneACTG1C0033377Ptosis1GENOMICS_ENGLAND
HgeneACTG1C0205696Anaplastic carcinoma1CTD_human
HgeneACTG1C0205697Carcinoma, Spindle-Cell1CTD_human
HgeneACTG1C0205698Undifferentiated carcinoma1CTD_human
HgeneACTG1C0205699Carcinomatosis1CTD_human
HgeneACTG1C0240583Short upturned nose1GENOMICS_ENGLAND
HgeneACTG1C0265541Cranioschisis1CTD_human
HgeneACTG1C0266551Congenital coloboma of iris1ORPHANET
HgeneACTG1C0376634Craniofacial Abnormalities1CTD_human
HgeneACTG1C0497552Congenital neurologic anomalies1CTD_human
HgeneACTG1C0751406Post-Traumatic Osteoporosis1CTD_human
HgeneACTG1C0857379Abnormality of the pinna1GENOMICS_ENGLAND
HgeneACTG1C0948089Acute Coronary Syndrome1CTD_human
HgeneACTG1C1257925Mammary Carcinoma, Animal1CTD_human
HgeneACTG1C1384666hearing impairment1GENOMICS_ENGLAND
HgeneACTG1C1843156Progressive sensorineural hearing impairment1GENOMICS_ENGLAND
HgeneACTG1C1844505Pointed chin1GENOMICS_ENGLAND
HgeneACTG1C1849340Long palpebral fissure1GENOMICS_ENGLAND
HgeneACTG1C1855722Iris Coloboma with Ptosis, Hypertelorism, and Mental Retardation1ORPHANET
HgeneACTG1C1865014Long philtrum1GENOMICS_ENGLAND
HgeneACTG1C1865017Thin upper lip vermilion1GENOMICS_ENGLAND
HgeneACTG1C1868571Highly arched eyebrow1GENOMICS_ENGLAND
HgeneACTG1C1970280Hearing loss begins with loss of high frequencies1GENOMICS_ENGLAND
HgeneACTG1C1970281Audiogram shows sloping configuration1GENOMICS_ENGLAND
HgeneACTG1C1970282Deafness, profound, by 6th decade1GENOMICS_ENGLAND
HgeneACTG1C3279369Microphthalmia (in some patients)1GENOMICS_ENGLAND
HgeneACTG1C3549665Deafness (in some patients)1GENOMICS_ENGLAND
HgeneACTG1C3808883Short neck (in some patients)1GENOMICS_ENGLAND
HgeneACTG1C4012410Enlarged ventricles (in some patients)1GENOMICS_ENGLAND
HgeneACTG1C4229649Heart defect (in some patients)1GENOMICS_ENGLAND
HgeneACTG1C4229650Pterygium colli (in some patients)1GENOMICS_ENGLAND
HgeneACTG1C4229651Hypertelorism/telecanthus1GENOMICS_ENGLAND
HgeneACTG1C4229652Eye coloboma (in some patients)1GENOMICS_ENGLAND
HgeneACTG1C4229653Trigonocephaly/metopic ridge1GENOMICS_ENGLAND
HgeneACTG1C4231117Pectus (in some patients)1GENOMICS_ENGLAND
HgeneACTG1C4231118Kyphosis/scoliosis (in some patients)1GENOMICS_ENGLAND
HgeneACTG1C4231120Prominent nasal root on profile1GENOMICS_ENGLAND
HgeneACTG1C4231121Large, squared nose tip1GENOMICS_ENGLAND
HgeneACTG1C4231123Retrognathia (in some patients)1GENOMICS_ENGLAND
HgeneACTG1C4231124Prominent/full/wide cheeks1GENOMICS_ENGLAND
HgeneACTG1C4554007Uveoretinal Coloboma1CTD_human
HgeneACTG1C4708599Coloboma of choroid and retina1ORPHANET