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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:PICALM-CTSC

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PICALM-CTSC
FusionPDB ID: 65146
FusionGDB2.0 ID: 65146
HgeneTgene
Gene symbol

PICALM

CTSC

Gene ID

8301

1075

Gene namephosphatidylinositol binding clathrin assembly proteincathepsin C
SynonymsCALM|CLTH|LAPCPPI|DPP-I|DPP1|DPPI|HMS|JP|JPD|PALS|PDON1|PLS
Cytomap

11q14.2

11q14.2

Type of geneprotein-codingprotein-coding
Descriptionphosphatidylinositol-binding clathrin assembly proteinclathrin assembly lymphoid myeloid leukemia proteindipeptidyl peptidase 1cathepsin Jdipeptidyl transferasedipeptidyl-peptidase I
Modification date2020032220200313
UniProtAcc

Q13492

Main function of 5'-partner protein: FUNCTION: Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly (PubMed:10436022, PubMed:16262731, PubMed:27574975). Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature (PubMed:25898166). In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8 (PubMed:22118466, PubMed:21808019, PubMed:23741335). In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors (PubMed:25241929). Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF) (PubMed:25241929, PubMed:24067654). {ECO:0000269|PubMed:10436022, ECO:0000269|PubMed:16262731, ECO:0000269|PubMed:21808019, ECO:0000269|PubMed:22118466, ECO:0000269|PubMed:23741335, ECO:0000269|PubMed:24067654, ECO:0000269|PubMed:25241929, ECO:0000269|PubMed:25898166, ECO:0000269|PubMed:27574975}.

P53634

Main function of 5'-partner protein: FUNCTION: Thiol protease. Has dipeptidylpeptidase activity. Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids. Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate. Can act as both an exopeptidase and endopeptidase. Activates serine proteases such as elastase, cathepsin G and granzymes A and B. Can also activate neuraminidase and factor XIII. {ECO:0000269|PubMed:1586157}.
Ensembl transtripts involved in fusion geneENST idsENST00000356360, ENST00000393346, 
ENST00000526033, ENST00000532317, 
ENST00000528411, ENST00000528398, 
ENST00000393301, ENST00000524463, 
ENST00000529974, ENST00000227266, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score24 X 29 X 9=62646 X 4 X 4=96
# samples 396
** MAII scorelog2(39/6264*10)=-4.00553818354143
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/96*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PICALM [Title/Abstract] AND CTSC [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PICALM [Title/Abstract] AND CTSC [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PICALM(85779693)-CTSC(88045722), # samples:1
Anticipated loss of major functional domain due to fusion event.PICALM-CTSC 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.
PICALM-CTSC 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
HgenePICALM

GO:0006897

endocytosis

22118466

HgenePICALM

GO:0006898

receptor-mediated endocytosis

10436022

HgenePICALM

GO:0032880

regulation of protein localization

10436022

HgenePICALM

GO:0045893

positive regulation of transcription, DNA-templated

11425879

HgenePICALM

GO:0048261

negative regulation of receptor-mediated endocytosis

10436022

HgenePICALM

GO:1905224

clathrin-coated pit assembly

16262731

TgeneCTSC

GO:0006508

proteolysis

8811434



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/chr11:85779693/chr11:88045722)
- 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 PICALM (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 CTSC (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)
ENST00000532317PICALMchr1185779693-ENST00000227266CTSCchr1188045722-18974093101482390
ENST00000526033PICALMchr1185779693-ENST00000227266CTSCchr1188045722-19354473481520390
ENST00000393346PICALMchr1185779693-ENST00000227266CTSCchr1188045722-17672791801352390
ENST00000356360PICALMchr1185779693-ENST00000227266CTSCchr1188045722-1618130311203390

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
ENST00000532317ENST00000227266PICALMchr1185779693-CTSCchr1188045722-0.0016318230.9983682
ENST00000526033ENST00000227266PICALMchr1185779693-CTSCchr1188045722-0.0016777530.9983222
ENST00000393346ENST00000227266PICALMchr1185779693-CTSCchr1188045722-0.0014930090.99850696
ENST00000356360ENST00000227266PICALMchr1185779693-CTSCchr1188045722-0.0012359010.99876416

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 PICALM-CTSC

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PICALMchr1185779693CTSCchr118804572213033PTRSWGPRKSTWTYKEEGSKVTTYCN
PICALMchr1185779693CTSCchr118804572227933PTRSWGPRKSTWTYKEEGSKVTTYCN
PICALMchr1185779693CTSCchr118804572240933PTRSWGPRKSTWTYKEEGSKVTTYCN
PICALMchr1185779693CTSCchr118804572244733PTRSWGPRKSTWTYKEEGSKVTTYCN

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Potential FusionNeoAntigen Information of PICALM-CTSC 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.
PICALM-CTSC_85779693_88045722.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)
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:01GPRKSTWTY0.87790.7372514
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:08GPRKSTWTY0.82690.678514
PICALM-CTSCchr1185779693chr1188045722130HLA-B15:02GPRKSTWTY0.72860.8301514
PICALM-CTSCchr1185779693chr1188045722130HLA-B15:31GPRKSTWTY0.86310.6997514
PICALM-CTSCchr1185779693chr1188045722130HLA-B15:21GPRKSTWTY0.71120.7812514
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:77GPRKSTWTY0.87790.7372514
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:23GPRKSTWTY0.87480.738514
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:20GPRKSTWTY0.85020.8125514
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:11GPRKSTWTY0.74280.7575514
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:30GPRKSTWTY0.74280.5034514
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:17GPRKSTWTY0.74280.5034514
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:24GPRKSTWTY0.70560.7378514
PICALM-CTSCchr1185779693chr1188045722130HLA-B15:11GPRKSTWTY0.26910.6488514
PICALM-CTSCchr1185779693chr1188045722130HLA-B15:08GPRKSTWTY0.25840.6665514
PICALM-CTSCchr1185779693chr1188045722130HLA-B18:04GPRKSTWTY0.23840.7211514
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:43GPRKSTWTY0.22980.6715514
PICALM-CTSCchr1185779693chr1188045722130HLA-C07:04TYKEEGSKV0.11730.92571221
PICALM-CTSCchr1185779693chr1188045722130HLA-B18:07GPRKSTWTY0.07910.6067514
PICALM-CTSCchr1185779693chr1188045722130HLA-B18:03GPRKSTWTY0.07330.6777514
PICALM-CTSCchr1185779693chr1188045722130HLA-C14:03TYKEEGSKV0.05840.9551221
PICALM-CTSCchr1185779693chr1188045722130HLA-C14:02TYKEEGSKV0.05840.9551221
PICALM-CTSCchr1185779693chr1188045722130HLA-C06:06TYKEEGSKV0.04910.98031221
PICALM-CTSCchr1185779693chr1188045722130HLA-B15:11WGPRKSTWTY0.9590.6929414
PICALM-CTSCchr1185779693chr1188045722130HLA-B15:08WGPRKSTWTY0.95450.7128414
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:43WGPRKSTWTY0.94370.7197414
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:11WGPRKSTWTY0.9090.7944414
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:30WGPRKSTWTY0.85370.5601414
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:17WGPRKSTWTY0.85370.5601414
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:24WGPRKSTWTY0.72470.7707414
PICALM-CTSCchr1185779693chr1188045722130HLA-B15:11SWGPRKSTWTY0.98680.7564314
PICALM-CTSCchr1185779693chr1188045722130HLA-B15:08SWGPRKSTWTY0.98620.767314
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:30SWGPRKSTWTY0.93540.6032314
PICALM-CTSCchr1185779693chr1188045722130HLA-B35:17SWGPRKSTWTY0.93540.6032314

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Potential FusionNeoAntigen Information of PICALM-CTSC 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 PICALM-CTSC

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
6951PRKSTWTYKEEGSKPICALMCTSCchr1185779693chr1188045722130

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PICALM-CTSC

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-B14:023BVN6951PRKSTWTYKEEGSK-7.1232-8.704
HLA-B14:023BVN6951PRKSTWTYKEEGSK-7.05814-8.14544
HLA-B14:023BVN6951PRKSTWTYKEEGSK-6.80137-6.96677
HLA-B14:023BVN6951PRKSTWTYKEEGSK-6.27736-6.44276
HLA-B14:023BVN6951PRKSTWTYKEEGSK-5.66303-6.75033
HLA-B14:023BVN6951PRKSTWTYKEEGSK-3.26408-4.84488
HLA-B52:013W396951PRKSTWTYKEEGSK-6.82844-6.99384
HLA-B52:013W396951PRKSTWTYKEEGSK-5.9892-6.1546
HLA-B52:013W396951PRKSTWTYKEEGSK-5.15644-6.73724
HLA-B52:013W396951PRKSTWTYKEEGSK-4.93629-6.51709
HLA-B52:013W396951PRKSTWTYKEEGSK-4.84337-5.93067
HLA-B52:013W396951PRKSTWTYKEEGSK-4.42724-5.51454
HLA-A11:014UQ26951PRKSTWTYKEEGSK-8.65347-10.2343
HLA-A11:014UQ26951PRKSTWTYKEEGSK-2.66636-3.75366
HLA-A24:025HGA6951PRKSTWTYKEEGSK-7.31593-7.48133
HLA-A24:025HGA6951PRKSTWTYKEEGSK-7.20956-7.37496
HLA-A24:025HGA6951PRKSTWTYKEEGSK-5.89882-7.47962
HLA-A24:025HGA6951PRKSTWTYKEEGSK-5.38649-6.47379
HLA-A24:025HGA6951PRKSTWTYKEEGSK-5.26795-6.84875
HLA-A24:025HGA6951PRKSTWTYKEEGSK-5.08842-6.17572
HLA-B27:056PYJ6951PRKSTWTYKEEGSK-6.47792-6.64332
HLA-B27:036PZ56951PRKSTWTYKEEGSK-4.64431-6.22511
HLA-B44:053DX86951PRKSTWTYKEEGSK-6.55121-6.71661
HLA-B44:053DX86951PRKSTWTYKEEGSK-6.1116-7.6924
HLA-B44:053DX86951PRKSTWTYKEEGSK-5.82456-7.40536
HLA-B44:053DX86951PRKSTWTYKEEGSK-5.35458-5.51998
HLA-B44:053DX86951PRKSTWTYKEEGSK-5.15077-6.23807
HLA-B44:053DX86951PRKSTWTYKEEGSK-4.83856-5.92586

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Vaccine Design for the FusionNeoAntigens of PICALM-CTSC

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
PICALM-CTSCchr1185779693chr11880457221221TYKEEGSKVACTTATAAAGAAGAGGGCAGCAAGGTG
PICALM-CTSCchr1185779693chr1188045722314SWGPRKSTWTYTCATGGGGCCCAAGAAAAAGCACCTGGACTTAT
PICALM-CTSCchr1185779693chr1188045722414WGPRKSTWTYTGGGGCCCAAGAAAAAGCACCTGGACTTAT
PICALM-CTSCchr1185779693chr1188045722514GPRKSTWTYGGCCCAAGAAAAAGCACCTGGACTTAT

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 PICALM-CTSC

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
STADPICALM-CTSCchr1185779693ENST00000356360chr1188045722ENST00000227266TCGA-D7-A4Z0-01A

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Potential target of CAR-T therapy development for PICALM-CTSC

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 PICALM-CTSC

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 PICALM-CTSC

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
HgenePICALMC0002395Alzheimer's Disease2CTD_human
HgenePICALMC0011265Presenile dementia2CTD_human
HgenePICALMC0276496Familial Alzheimer Disease (FAD)2CTD_human
HgenePICALMC0494463Alzheimer Disease, Late Onset2CTD_human
HgenePICALMC0546126Acute Confusional Senile Dementia2CTD_human
HgenePICALMC0750900Alzheimer's Disease, Focal Onset2CTD_human
HgenePICALMC0750901Alzheimer Disease, Early Onset2CTD_human
HgenePICALMC0234985Mental deterioration1CTD_human
HgenePICALMC0338656Impaired cognition1CTD_human
HgenePICALMC1270972Mild cognitive disorder1CTD_human