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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:LPCAT1-SDHA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LPCAT1-SDHA
FusionPDB ID: 49492
FusionGDB2.0 ID: 49492
HgeneTgene
Gene symbol

LPCAT1

SDHA

Gene ID

79888

6389

Gene namelysophosphatidylcholine acyltransferase 1succinate dehydrogenase complex flavoprotein subunit A
SynonymsAGPAT10|AGPAT9|AYTL2|LPCAT-1|PFAAP3|lpcat|lysoPAFATCMD1GG|FP|PGL5|SDH1|SDH2|SDHF
Cytomap

5p15.33

5p15.33

Type of geneprotein-codingprotein-coding
Descriptionlysophosphatidylcholine acyltransferase 11-acylglycerophosphocholine O-acyltransferase1-alkylglycerophosphocholine O-acetyltransferaseLPC acyltransferase 1acetyl-CoA:lyso-PAF acetyltransferaseacetyl-CoA:lyso-platelet-activating factor acetyltransferasuccinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrialflavoprotein subunit of complex IIsuccinate dehydrogenase complex, subunit A, flavoprotein (Fp)
Modification date2020031320200313
UniProtAcc

Q8NF37

Main function of 5'-partner protein: FUNCTION: Exhibits acyltransferase activity (PubMed:21498505, PubMed:18156367). Exhibits acetyltransferase activity (By similarity). Activity is calcium-independent (By similarity). Catalyzes the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:21498505, PubMed:18156367). Catalyzes the conversion 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity). Displays a clear preference for saturated fatty acyl-CoAs, and 1-myristoyl or 1-palmitoyl LPC as acyl donors and acceptors, respectively (By similarity). Involved in platelet-activating factor (PAF) biosynthesis by catalyzing the conversion of the PAF precursor, 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) into 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) (By similarity). May synthesize phosphatidylcholine in pulmonary surfactant, thereby playing a pivotal role in respiratory physiology (By similarity). Involved in the regulation of lipid droplet number and size (PubMed:25491198). {ECO:0000250|UniProtKB:Q3TFD2, ECO:0000269|PubMed:18156367, ECO:0000269|PubMed:21498505, ECO:0000269|PubMed:25491198}.

Q5VUM1

Main function of 5'-partner protein: FUNCTION: Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol (PubMed:24954416). Binds to the flavoprotein subunit SDHA in its FAD-bound form, blocking the generation of excess reactive oxigen species (ROS) and facilitating its assembly with the iron-sulfur protein subunit SDHB into the SDH catalytic dimer (By similarity). {ECO:0000250|UniProtKB:P38345, ECO:0000269|PubMed:24954416}.
Ensembl transtripts involved in fusion geneENST idsENST00000283415, ENST00000503252, 
ENST00000504309, ENST00000507522, 
ENST00000510361, ENST00000264932, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 8 X 6=4325 X 7 X 5=175
# samples 127
** MAII scorelog2(12/432*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/175*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LPCAT1 [Title/Abstract] AND SDHA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LPCAT1 [Title/Abstract] AND SDHA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LPCAT1(1488506)-SDHA(251453), # samples:1
Anticipated loss of major functional domain due to fusion event.LPCAT1-SDHA 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.
LPCAT1-SDHA 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.
LPCAT1-SDHA 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.
LPCAT1-SDHA 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
HgeneLPCAT1

GO:0036151

phosphatidylcholine acyl-chain remodeling

21498505

TgeneSDHA

GO:0006105

succinate metabolic process

7550341

TgeneSDHA

GO:0022904

respiratory electron transport chain

7550341

TgeneSDHA

GO:0055114

oxidation-reduction process

7550341



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/chr5:1488506/chr5:251453)
- 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 LPCAT1 (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 SDHA (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)
ENST00000283415LPCAT1chr51488506-ENST00000264932SDHAchr5251453+14128001061131341

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
ENST00000283415ENST00000264932LPCAT1chr51488506-SDHAchr5251453+0.0124955830.9875044

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 LPCAT1-SDHA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LPCAT1chr51488506SDHAchr5251453800230GTCTNRTCLITFKPGMVWNTDLVETL

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Potential FusionNeoAntigen Information of LPCAT1-SDHA 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.
LPCAT1-SDHA_1488506_251453.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)
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:01TFKPGMVW0.99760.98941018
LPCAT1-SDHAchr51488506chr5251453800HLA-B58:02TFKPGMVW0.99330.99091018
LPCAT1-SDHAchr51488506chr5251453800HLA-B58:01TFKPGMVW0.97250.98851018
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:01ITFKPGMVW0.99970.9669918
LPCAT1-SDHAchr51488506chr5251453800HLA-B58:02ITFKPGMVW0.99940.9542918
LPCAT1-SDHAchr51488506chr5251453800HLA-B58:01ITFKPGMVW0.99930.9156918
LPCAT1-SDHAchr51488506chr5251453800HLA-B15:17ITFKPGMVW0.99770.8773918
LPCAT1-SDHAchr51488506chr5251453800HLA-B15:16ITFKPGMVW0.9970.8033918
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:03ITFKPGMVW0.9960.9775918
LPCAT1-SDHAchr51488506chr5251453800HLA-A31:08ITFKPGMVW0.98590.6809918
LPCAT1-SDHAchr51488506chr5251453800HLA-A32:13ITFKPGMVW0.93490.9859918
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:01LITFKPGMVW0.99920.9693818
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:01ITFKPGMVWN0.99720.9601919
LPCAT1-SDHAchr51488506chr5251453800HLA-B58:02LITFKPGMVW0.99660.9617818
LPCAT1-SDHAchr51488506chr5251453800HLA-B58:01LITFKPGMVW0.98770.932818
LPCAT1-SDHAchr51488506chr5251453800HLA-B15:17LITFKPGMVW0.97520.8608818
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:03LITFKPGMVW0.96680.9796818
LPCAT1-SDHAchr51488506chr5251453800HLA-B15:16LITFKPGMVW0.95520.8349818
LPCAT1-SDHAchr51488506chr5251453800HLA-A32:13LITFKPGMVW0.94570.9574818
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:01CLITFKPGMVW0.99930.9867718
LPCAT1-SDHAchr51488506chr5251453800HLA-C15:04ITFKPGMVW0.83790.8496918
LPCAT1-SDHAchr51488506chr5251453800HLA-C03:14ITFKPGMVW0.35590.9873918
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:10TFKPGMVW0.99760.98941018
LPCAT1-SDHAchr51488506chr5251453800HLA-B58:06TFKPGMVW0.99490.99521018
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:10ITFKPGMVW0.99970.9669918
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:04ITFKPGMVW0.99950.6908918
LPCAT1-SDHAchr51488506chr5251453800HLA-B58:06ITFKPGMVW0.99890.8981918
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:02ITFKPGMVW0.99620.9085918
LPCAT1-SDHAchr51488506chr5251453800HLA-A32:01ITFKPGMVW0.98890.9917918
LPCAT1-SDHAchr51488506chr5251453800HLA-B15:13ITFKPGMVW0.98350.7619918
LPCAT1-SDHAchr51488506chr5251453800HLA-B15:24ITFKPGMVW0.86290.9119918
LPCAT1-SDHAchr51488506chr5251453800HLA-C15:09ITFKPGMVW0.83790.8496918
LPCAT1-SDHAchr51488506chr5251453800HLA-B53:02ITFKPGMVW0.68380.788918
LPCAT1-SDHAchr51488506chr5251453800HLA-C03:02ITFKPGMVW0.59890.9734918
LPCAT1-SDHAchr51488506chr5251453800HLA-A25:01ITFKPGMVW0.2060.9604918
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:10LITFKPGMVW0.99920.9693818
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:10ITFKPGMVWN0.99720.9601919
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:04LITFKPGMVW0.99590.723818
LPCAT1-SDHAchr51488506chr5251453800HLA-B58:06LITFKPGMVW0.99580.9262818
LPCAT1-SDHAchr51488506chr5251453800HLA-B58:06ITFKPGMVWN0.990.9165919
LPCAT1-SDHAchr51488506chr5251453800HLA-B15:24LITFKPGMVW0.98460.8994818
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:02LITFKPGMVW0.9790.9332818
LPCAT1-SDHAchr51488506chr5251453800HLA-B15:13LITFKPGMVW0.95010.7607818
LPCAT1-SDHAchr51488506chr5251453800HLA-A32:01LITFKPGMVW0.94290.9846818
LPCAT1-SDHAchr51488506chr5251453800HLA-B57:10CLITFKPGMVW0.99930.9867718

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Potential FusionNeoAntigen Information of LPCAT1-SDHA 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 LPCAT1-SDHA

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
9266TCLITFKPGMVWNTLPCAT1SDHAchr51488506chr5251453800

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LPCAT1-SDHA

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-B14:023BVN9266TCLITFKPGMVWNT-5.50071-6.53601
HLA-B14:023BVN9266TCLITFKPGMVWNT-5.44997-5.56337
HLA-B52:013W399266TCLITFKPGMVWNT-6.87928-6.99268
HLA-B52:013W399266TCLITFKPGMVWNT-3.95744-4.99274
HLA-A24:025HGA9266TCLITFKPGMVWNT-7.30598-7.41938
HLA-A24:025HGA9266TCLITFKPGMVWNT-5.09366-6.12896
HLA-B44:053DX89266TCLITFKPGMVWNT-5.64505-5.75845
HLA-B44:053DX89266TCLITFKPGMVWNT-4.1878-5.2231
HLA-A02:016TDR9266TCLITFKPGMVWNT-0.0912853-1.12659

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Vaccine Design for the FusionNeoAntigens of LPCAT1-SDHA

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
LPCAT1-SDHAchr51488506chr52514531018TFKPGMVWTCAAACCTGGAATGGTCTGGAACA
LPCAT1-SDHAchr51488506chr5251453718CLITFKPGMVWTAATTACCTTCAAACCTGGAATGGTCTGGAACA
LPCAT1-SDHAchr51488506chr5251453818LITFKPGMVWTTACCTTCAAACCTGGAATGGTCTGGAACA
LPCAT1-SDHAchr51488506chr5251453918ITFKPGMVWCCTTCAAACCTGGAATGGTCTGGAACA
LPCAT1-SDHAchr51488506chr5251453919ITFKPGMVWNCCTTCAAACCTGGAATGGTCTGGAACACGG

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 LPCAT1-SDHA

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
LUADLPCAT1-SDHAchr51488506ENST00000283415chr5251453ENST00000264932TCGA-55-8506-01A

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Potential target of CAR-T therapy development for LPCAT1-SDHA

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
HgeneLPCAT1chr5:1488506chr5:251453ENST00000283415-51458_78222535.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

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 LPCAT1-SDHA

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 LPCAT1-SDHA

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