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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:AGPS-LMNA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: AGPS-LMNA
FusionPDB ID: 2980
FusionGDB2.0 ID: 2980
HgeneTgene
Gene symbol

AGPS

LMNA

Gene ID

8540

4000

Gene namealkylglycerone phosphate synthaselamin A/C
SynonymsADAP-S|ADAS|ADHAPS|ADPS|ALDHPSY|RCDP3CDCD1|CDDC|CMD1A|CMT2B1|EMD2|FPL|FPLD|FPLD2|HGPS|IDC|LDP1|LFP|LGMD1B|LMN1|LMNC|LMNL1|MADA|PRO1
Cytomap

2q31.2

1q22

Type of geneprotein-codingprotein-coding
Descriptionalkyldihydroxyacetonephosphate synthase, peroxisomalaging-associated gene 5 proteinaging-associated protein 5alkyl-DHAP synthaselamin70 kDa laminepididymis secretory sperm binding proteinlamin A/C-like 1mandibuloacral dysplasia type Aprelamin-A/Crenal carcinoma antigen NY-REN-32
Modification date2020031320200329
UniProtAcc

O00116

Main function of 5'-partner protein: FUNCTION: Catalyzes the exchange of the acyl chain in acyl-dihydroxyacetonephosphate (acyl-DHAP) for a long chain fatty alcohol, yielding the first ether linked intermediate, i.e. alkyl-dihydroxyacetonephosphate (alkyl-DHAP), in the pathway of ether lipid biosynthesis. {ECO:0000269|PubMed:8399344, ECO:0000269|PubMed:9553082}.

P02545

Main function of 5'-partner protein: FUNCTION: Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:22431096, PubMed:10814726, PubMed:11799477, PubMed:18551513). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:31548606}.; FUNCTION: Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.
Ensembl transtripts involved in fusion geneENST idsENST00000264167, ENST00000409888, 
ENST00000496738, ENST00000347559, 
ENST00000361308, ENST00000368297, 
ENST00000368299, ENST00000368300, 
ENST00000368301, ENST00000392353, 
ENST00000448611, ENST00000473598, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 8 X 7=44813 X 16 X 6=1248
# samples 1016
** MAII scorelog2(10/448*10)=-2.16349873228288
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1248*10)=-2.96347412397489
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: AGPS [Title/Abstract] AND LMNA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: AGPS [Title/Abstract] AND LMNA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)AGPS(178310354)-LMNA(156104595), # samples:1
Anticipated loss of major functional domain due to fusion event.AGPS-LMNA 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.
AGPS-LMNA 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.
AGPS-LMNA 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.
AGPS-LMNA 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
HgeneAGPS

GO:0008610

lipid biosynthetic process

9553082

TgeneLMNA

GO:0090343

positive regulation of cell aging

20458013



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/chr2:178310354/chr1:156104595)
- 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 AGPS (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 LMNA (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)
ENST00000264167AGPSchr2178310354+ENST00000368301LMNAchr1156104595+21971016682095675
ENST00000264167AGPSchr2178310354+ENST00000361308LMNAchr1156104595+21971016682095675
ENST00000264167AGPSchr2178310354+ENST00000347559LMNAchr1156104595+32631016682281737
ENST00000264167AGPSchr2178310354+ENST00000368300LMNAchr1156104595+33551016682371767
ENST00000264167AGPSchr2178310354+ENST00000368299LMNAchr1156104595+24331016682221717
ENST00000264167AGPSchr2178310354+ENST00000448611LMNAchr1156104595+26121016682437789
ENST00000264167AGPSchr2178310354+ENST00000368297LMNAchr1156104595+21971016682095675
ENST00000264167AGPSchr2178310354+ENST00000473598LMNAchr1156104595+25691016682371767
ENST00000264167AGPSchr2178310354+ENST00000392353LMNAchr1156104595+21971016682095675

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
ENST00000264167ENST00000368301AGPSchr2178310354+LMNAchr1156104595+0.0144243240.9855757
ENST00000264167ENST00000361308AGPSchr2178310354+LMNAchr1156104595+0.0144243240.9855757
ENST00000264167ENST00000347559AGPSchr2178310354+LMNAchr1156104595+0.009352090.99064785
ENST00000264167ENST00000368300AGPSchr2178310354+LMNAchr1156104595+0.0072980890.9927019
ENST00000264167ENST00000368299AGPSchr2178310354+LMNAchr1156104595+0.0157750160.98422503
ENST00000264167ENST00000448611AGPSchr2178310354+LMNAchr1156104595+0.0104699840.98953
ENST00000264167ENST00000368297AGPSchr2178310354+LMNAchr1156104595+0.0144243240.9855757
ENST00000264167ENST00000473598AGPSchr2178310354+LMNAchr1156104595+0.0140604870.9859395
ENST00000264167ENST00000392353AGPSchr2178310354+LMNAchr1156104595+0.0144243240.9855757

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 AGPS-LMNA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
AGPSchr2178310354LMNAchr11561045951016315HVEAGITGQELERQELRETKRRHETR

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Potential FusionNeoAntigen Information of AGPS-LMNA 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.
AGPS-LMNA_178310354_156104595.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)
AGPS-LMNAchr2178310354chr11561045951016HLA-B39:13QELERQEL0.99620.9587816
AGPS-LMNAchr2178310354chr11561045951016HLA-B18:01QELERQEL0.98790.8895816
AGPS-LMNAchr2178310354chr11561045951016HLA-B39:13GQELERQEL0.93320.9203716
AGPS-LMNAchr2178310354chr11561045951016HLA-B13:01GQELERQEL0.92870.9592716
AGPS-LMNAchr2178310354chr11561045951016HLA-B39:08QELERQEL0.99690.9445816
AGPS-LMNAchr2178310354chr11561045951016HLA-B39:08GQELERQEL0.96690.9182716
AGPS-LMNAchr2178310354chr11561045951016HLA-B40:04QELERQEL0.99980.7773816
AGPS-LMNAchr2178310354chr11561045951016HLA-B18:11QELERQEL0.99830.8969816
AGPS-LMNAchr2178310354chr11561045951016HLA-B39:02QELERQEL0.99740.9594816
AGPS-LMNAchr2178310354chr11561045951016HLA-B41:03QELERQEL0.99590.7782816
AGPS-LMNAchr2178310354chr11561045951016HLA-B18:06QELERQEL0.99120.8992816
AGPS-LMNAchr2178310354chr11561045951016HLA-B18:03QELERQEL0.98970.8813816
AGPS-LMNAchr2178310354chr11561045951016HLA-B18:05QELERQEL0.98790.8895816
AGPS-LMNAchr2178310354chr11561045951016HLA-B39:02GQELERQEL0.96220.9206716
AGPS-LMNAchr2178310354chr11561045951016HLA-B39:11GQELERQEL0.93830.8652716
AGPS-LMNAchr2178310354chr11561045951016HLA-B15:73GQELERQEL0.78480.8238716
AGPS-LMNAchr2178310354chr11561045951016HLA-B15:30GQELERQEL0.77110.8515716

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Potential FusionNeoAntigen Information of AGPS-LMNA 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.
AGPS-LMNA_178310354_156104595.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)
AGPS-LMNAchr2178310354chr11561045951016DRB1-1332ERQELRETKRRHETR1126
AGPS-LMNAchr2178310354chr11561045951016DRB1-1348ERQELRETKRRHETR1126
AGPS-LMNAchr2178310354chr11561045951016DRB1-1375ERQELRETKRRHETR1126
AGPS-LMNAchr2178310354chr11561045951016DRB4-0101EAGITGQELERQELR217
AGPS-LMNAchr2178310354chr11561045951016DRB4-0101VEAGITGQELERQEL116
AGPS-LMNAchr2178310354chr11561045951016DRB4-0101HVEAGITGQELERQE015
AGPS-LMNAchr2178310354chr11561045951016DRB4-0101AGITGQELERQELRE318
AGPS-LMNAchr2178310354chr11561045951016DRB4-0103EAGITGQELERQELR217
AGPS-LMNAchr2178310354chr11561045951016DRB4-0103VEAGITGQELERQEL116
AGPS-LMNAchr2178310354chr11561045951016DRB4-0103HVEAGITGQELERQE015
AGPS-LMNAchr2178310354chr11561045951016DRB4-0103AGITGQELERQELRE318
AGPS-LMNAchr2178310354chr11561045951016DRB4-0104EAGITGQELERQELR217
AGPS-LMNAchr2178310354chr11561045951016DRB4-0104VEAGITGQELERQEL116
AGPS-LMNAchr2178310354chr11561045951016DRB4-0104HVEAGITGQELERQE015
AGPS-LMNAchr2178310354chr11561045951016DRB4-0104AGITGQELERQELRE318
AGPS-LMNAchr2178310354chr11561045951016DRB4-0104GQELERQELRETKRR722
AGPS-LMNAchr2178310354chr11561045951016DRB4-0106EAGITGQELERQELR217
AGPS-LMNAchr2178310354chr11561045951016DRB4-0106VEAGITGQELERQEL116
AGPS-LMNAchr2178310354chr11561045951016DRB4-0106HVEAGITGQELERQE015
AGPS-LMNAchr2178310354chr11561045951016DRB4-0106AGITGQELERQELRE318
AGPS-LMNAchr2178310354chr11561045951016DRB4-0107EAGITGQELERQELR217
AGPS-LMNAchr2178310354chr11561045951016DRB4-0107VEAGITGQELERQEL116
AGPS-LMNAchr2178310354chr11561045951016DRB4-0107HVEAGITGQELERQE015
AGPS-LMNAchr2178310354chr11561045951016DRB4-0107AGITGQELERQELRE318
AGPS-LMNAchr2178310354chr11561045951016DRB4-0108EAGITGQELERQELR217
AGPS-LMNAchr2178310354chr11561045951016DRB4-0108VEAGITGQELERQEL116
AGPS-LMNAchr2178310354chr11561045951016DRB4-0108HVEAGITGQELERQE015
AGPS-LMNAchr2178310354chr11561045951016DRB4-0108AGITGQELERQELRE318

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Fusion breakpoint peptide structures of AGPS-LMNA

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
9366TGQELERQELRETKAGPSLMNAchr2178310354chr11561045951016

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of AGPS-LMNA

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-B14:023BVN9366TGQELERQELRETK-7.9962-8.1096
HLA-B14:023BVN9366TGQELERQELRETK-5.70842-6.74372
HLA-B52:013W399366TGQELERQELRETK-6.83737-6.95077
HLA-B52:013W399366TGQELERQELRETK-4.4836-5.5189
HLA-A11:014UQ29366TGQELERQELRETK-10.0067-10.1201
HLA-A11:014UQ29366TGQELERQELRETK-9.03915-10.0745
HLA-A24:025HGA9366TGQELERQELRETK-6.56204-6.67544
HLA-A24:025HGA9366TGQELERQELRETK-5.42271-6.45801
HLA-B44:053DX89366TGQELERQELRETK-7.85648-8.89178
HLA-B44:053DX89366TGQELERQELRETK-5.3978-5.5112
HLA-A02:016TDR9366TGQELERQELRETK-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of AGPS-LMNA

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
AGPS-LMNAchr2178310354chr1156104595716GQELERQELCAAGAGTTGGAAAGACAGGAGCTGCGT
AGPS-LMNAchr2178310354chr1156104595816QELERQELGAGTTGGAAAGACAGGAGCTGCGT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
AGPS-LMNAchr2178310354chr1156104595015HVEAGITGQELERQEGTAGAGGCTGGCATAACAGGACAAGAGTTGGAAAGACAGGAGCTG
AGPS-LMNAchr2178310354chr1156104595116VEAGITGQELERQELGAGGCTGGCATAACAGGACAAGAGTTGGAAAGACAGGAGCTGCGT
AGPS-LMNAchr2178310354chr11561045951126ERQELRETKRRHETRAGACAGGAGCTGCGTGAGACCAAGCGCCGTCATGAGACCCGACTG
AGPS-LMNAchr2178310354chr1156104595217EAGITGQELERQELRGCTGGCATAACAGGACAAGAGTTGGAAAGACAGGAGCTGCGTGAG
AGPS-LMNAchr2178310354chr1156104595318AGITGQELERQELREGGCATAACAGGACAAGAGTTGGAAAGACAGGAGCTGCGTGAGACC
AGPS-LMNAchr2178310354chr1156104595722GQELERQELRETKRRCAAGAGTTGGAAAGACAGGAGCTGCGTGAGACCAAGCGCCGTCAT

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Information of the samples that have these potential fusion neoantigens of AGPS-LMNA

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
KIRCAGPS-LMNAchr2178310354ENST00000264167chr1156104595ENST00000347559TCGA-B0-5399

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Potential target of CAR-T therapy development for AGPS-LMNA

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 AGPS-LMNA

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 AGPS-LMNA

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