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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:LIPC-TCF12

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LIPC-TCF12
FusionPDB ID: 45627
FusionGDB2.0 ID: 45627
HgeneTgene
Gene symbol

LIPC

TCF12

Gene ID

3990

6938

Gene namelipase C, hepatic typetranscription factor 12
SynonymsHDLCQ12|HL|HTGL|LIPHCRS3|HEB|HTF4|HsT17266|TCF-12|bHLHb20|p64
Cytomap

15q21.3

15q21.3

Type of geneprotein-codingprotein-coding
Descriptionhepatic triacylglycerol lipaseTriacylglycerol lipasehepatic lipaselipase member Clipase, hepatictranscription factor 12DNA-binding protein HTF4E-box-binding proteinclass B basic helix-loop-helix protein 20helix-loop-helix transcription factor 4transcription factor HTF-4
Modification date2020032220200313
UniProtAcc

P11150

Main function of 5'-partner protein: FUNCTION: Catalyzes the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins, including chylomicrons, intermediate density lipoproteins (IDL), low density lipoproteins (LDL) of large size and high density lipoproteins (HDL), releasing free fatty acids (FFA) and smaller lipoprotein particles (PubMed:7592706, PubMed:8798474, PubMed:12032167, PubMed:26193433). Also exhibits lysophospholipase activity (By similarity). Can hydrolyze both neutral lipid and phospholipid substrates but shows a greater binding affinity for neutral lipid substrates than phospholipid substrates (By similarity). In native LDL, preferentially hydrolyzes the phosphatidylcholine species containing polyunsaturated fatty acids at sn-2 position (PubMed:26193433). {ECO:0000250|UniProtKB:P07867, ECO:0000269|PubMed:12032167, ECO:0000269|PubMed:26193433, ECO:0000269|PubMed:7592706, ECO:0000269|PubMed:8798474}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000299022, ENST00000356113, 
ENST00000414170, ENST00000433326, 
ENST00000343827, ENST00000537840, 
ENST00000543579, ENST00000559703, 
ENST00000559710, ENST00000560764, 
ENST00000267811, ENST00000333725, 
ENST00000438423, ENST00000452095, 
ENST00000557843, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 3 X 3=3621 X 22 X 8=3696
# samples 426
** MAII scorelog2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(26/3696*10)=-3.8293812283876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LIPC [Title/Abstract] AND TCF12 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LIPC [Title/Abstract] AND TCF12 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LIPC(58724319)-TCF12(57458600), # samples:2
Anticipated loss of major functional domain due to fusion event.LIPC-TCF12 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.
LIPC-TCF12 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.
LIPC-TCF12 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.
LIPC-TCF12 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
HgeneLIPC

GO:0006633

fatty acid biosynthetic process

182536

HgeneLIPC

GO:0019433

triglyceride catabolic process

182536|2839510|8640403

HgeneLIPC

GO:0034372

very-low-density lipoprotein particle remodeling

8640403

TgeneTCF12

GO:0045944

positive regulation of transcription by RNA polymerase II

11802795



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/chr15:58724319/chr15:57458600)
- 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 LIPC (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 TCF12 (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)
ENST00000356113LIPCchr1558724319+ENST00000438423TCF12chr1557458600+48687036152498627
ENST00000356113LIPCchr1558724319+ENST00000267811TCF12chr1557458600+61357036152426603
ENST00000356113LIPCchr1558724319+ENST00000452095TCF12chr1557458600+48687036152498627
ENST00000356113LIPCchr1558724319+ENST00000333725TCF12chr1557458600+48627036152498627
ENST00000356113LIPCchr1558724319+ENST00000557843TCF12chr1557458600+43677036152426603
ENST00000414170LIPCchr1558724319+ENST00000438423TCF12chr1557458600+45403752872170627
ENST00000414170LIPCchr1558724319+ENST00000267811TCF12chr1557458600+58073752872098603
ENST00000414170LIPCchr1558724319+ENST00000452095TCF12chr1557458600+45403752872170627
ENST00000414170LIPCchr1558724319+ENST00000333725TCF12chr1557458600+45343752872170627
ENST00000414170LIPCchr1558724319+ENST00000557843TCF12chr1557458600+40393752872098603
ENST00000299022LIPCchr1558724319+ENST00000438423TCF12chr1557458600+44883232352118627
ENST00000299022LIPCchr1558724319+ENST00000267811TCF12chr1557458600+57553232352046603
ENST00000299022LIPCchr1558724319+ENST00000452095TCF12chr1557458600+44883232352118627
ENST00000299022LIPCchr1558724319+ENST00000333725TCF12chr1557458600+44823232352118627
ENST00000299022LIPCchr1558724319+ENST00000557843TCF12chr1557458600+39873232352046603
ENST00000433326LIPCchr1558724319+ENST00000438423TCF12chr1557458600+4295130421925627
ENST00000433326LIPCchr1558724319+ENST00000267811TCF12chr1557458600+5562130421853603
ENST00000433326LIPCchr1558724319+ENST00000452095TCF12chr1557458600+4295130421925627
ENST00000433326LIPCchr1558724319+ENST00000333725TCF12chr1557458600+4289130421925627
ENST00000433326LIPCchr1558724319+ENST00000557843TCF12chr1557458600+3794130421853603

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
ENST00000356113ENST00000438423LIPCchr1558724319+TCF12chr1557458600+0.0016975550.99830246
ENST00000356113ENST00000267811LIPCchr1558724319+TCF12chr1557458600+0.00084460.9991554
ENST00000356113ENST00000452095LIPCchr1558724319+TCF12chr1557458600+0.0016975550.99830246
ENST00000356113ENST00000333725LIPCchr1558724319+TCF12chr1557458600+0.0017226910.9982773
ENST00000356113ENST00000557843LIPCchr1558724319+TCF12chr1557458600+0.0032801050.9967199
ENST00000414170ENST00000438423LIPCchr1558724319+TCF12chr1557458600+0.0016875180.9983125
ENST00000414170ENST00000267811LIPCchr1558724319+TCF12chr1557458600+0.000858180.9991418
ENST00000414170ENST00000452095LIPCchr1558724319+TCF12chr1557458600+0.0016875180.9983125
ENST00000414170ENST00000333725LIPCchr1558724319+TCF12chr1557458600+0.0017136370.9982863
ENST00000414170ENST00000557843LIPCchr1558724319+TCF12chr1557458600+0.0031193080.99688065
ENST00000299022ENST00000438423LIPCchr1558724319+TCF12chr1557458600+0.0011734090.99882656
ENST00000299022ENST00000267811LIPCchr1558724319+TCF12chr1557458600+0.0006638480.9993362
ENST00000299022ENST00000452095LIPCchr1558724319+TCF12chr1557458600+0.0011734090.99882656
ENST00000299022ENST00000333725LIPCchr1558724319+TCF12chr1557458600+0.0011908240.9988092
ENST00000299022ENST00000557843LIPCchr1558724319+TCF12chr1557458600+0.0021655830.9978344
ENST00000433326ENST00000438423LIPCchr1558724319+TCF12chr1557458600+0.0014664490.9985335
ENST00000433326ENST00000267811LIPCchr1558724319+TCF12chr1557458600+0.0007391590.99926084
ENST00000433326ENST00000452095LIPCchr1558724319+TCF12chr1557458600+0.0014664490.9985335
ENST00000433326ENST00000333725LIPCchr1558724319+TCF12chr1557458600+0.0014898680.99851006
ENST00000433326ENST00000557843LIPCchr1558724319+TCF12chr1557458600+0.0026801390.9973199

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 LIPC-TCF12

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LIPCchr1558724319TCF12chr155745860013029FIQSSALGQSLKPGKTSERGSFSLYS
LIPCchr1558724319TCF12chr155745860032329FIQSSALGQSLKPGKTSERGSFSLYS
LIPCchr1558724319TCF12chr155745860037529FIQSSALGQSLKPGKTSERGSFSLYS
LIPCchr1558724319TCF12chr155745860070329FIQSSALGQSLKPGKTSERGSFSLYS

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Potential FusionNeoAntigen Information of LIPC-TCF12 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.
LIPC-TCF12_58724319_57458600.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)
LIPC-TCF12chr1558724319chr1557458600323HLA-A31:02SLKPGKTSER0.94430.5951919
LIPC-TCF12chr1558724319chr1557458600323HLA-A74:09SLKPGKTSER0.93280.6051919
LIPC-TCF12chr1558724319chr1557458600323HLA-A74:11SLKPGKTSER0.93280.6051919
LIPC-TCF12chr1558724319chr1557458600323HLA-A74:03SLKPGKTSER0.93280.6051919
LIPC-TCF12chr1558724319chr1557458600323HLA-A31:01SLKPGKTSER0.95140.5614919
LIPC-TCF12chr1558724319chr1557458600323HLA-A74:01SLKPGKTSER0.93280.6051919

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Potential FusionNeoAntigen Information of LIPC-TCF12 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 LIPC-TCF12

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
5022LGQSLKPGKTSERGLIPCTCF12chr1558724319chr1557458600323

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LIPC-TCF12

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-B14:023BVN5022LGQSLKPGKTSERG-7.9962-8.1096
HLA-B14:023BVN5022LGQSLKPGKTSERG-5.70842-6.74372
HLA-B52:013W395022LGQSLKPGKTSERG-6.83737-6.95077
HLA-B52:013W395022LGQSLKPGKTSERG-4.4836-5.5189
HLA-A11:014UQ25022LGQSLKPGKTSERG-10.0067-10.1201
HLA-A11:014UQ25022LGQSLKPGKTSERG-9.03915-10.0745
HLA-A24:025HGA5022LGQSLKPGKTSERG-6.56204-6.67544
HLA-A24:025HGA5022LGQSLKPGKTSERG-5.42271-6.45801
HLA-B44:053DX85022LGQSLKPGKTSERG-7.85648-8.89178
HLA-B44:053DX85022LGQSLKPGKTSERG-5.3978-5.5112
HLA-A02:016TDR5022LGQSLKPGKTSERG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LIPC-TCF12

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
LIPC-TCF12chr1558724319chr1557458600919SLKPGKTSERGCCTGAAACCAGGAAAAACATCAGAGAGAG

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 LIPC-TCF12

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
LIHCLIPC-TCF12chr1558724319ENST00000299022chr1557458600ENST00000267811TCGA-BD-A3ER-01A

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Potential target of CAR-T therapy development for LIPC-TCF12

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 LIPC-TCF12

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 LIPC-TCF12

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