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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:TMOD3-PICALM

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TMOD3-PICALM
FusionPDB ID: 92334
FusionGDB2.0 ID: 92334
HgeneTgene
Gene symbol

TMOD3

PICALM

Gene ID

29766

8301

Gene nametropomodulin 3phosphatidylinositol binding clathrin assembly protein
SynonymsUTMODCALM|CLTH|LAP
Cytomap

15q21.2

11q14.2

Type of geneprotein-codingprotein-coding
Descriptiontropomodulin-3tropomodulin 3 (ubiquitous)ubiquitous tropomodulinphosphatidylinositol-binding clathrin assembly proteinclathrin assembly lymphoid myeloid leukemia protein
Modification date2020031320200322
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}.
Ensembl transtripts involved in fusion geneENST idsENST00000308580, ENST00000544199, 
ENST00000561136, 
ENST00000528411, 
ENST00000356360, ENST00000393346, 
ENST00000526033, ENST00000528398, 
ENST00000532317, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 8 X 6=43235 X 26 X 12=10920
# samples 1044
** MAII scorelog2(10/432*10)=-2.11103131238874
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(44/10920*10)=-4.63332552228256
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TMOD3 [Title/Abstract] AND PICALM [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TMOD3 [Title/Abstract] AND PICALM [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TMOD3(52194233)-PICALM(85722179), # samples:1
Anticipated loss of major functional domain due to fusion event.TMOD3-PICALM 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.
TMOD3-PICALM 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.
TMOD3-PICALM 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.
TMOD3-PICALM 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
TgenePICALM

GO:0006897

endocytosis

22118466

TgenePICALM

GO:0006898

receptor-mediated endocytosis

10436022

TgenePICALM

GO:0032880

regulation of protein localization

10436022

TgenePICALM

GO:0045893

positive regulation of transcription, DNA-templated

11425879

TgenePICALM

GO:0048261

negative regulation of receptor-mediated endocytosis

10436022

TgenePICALM

GO:1905224

clathrin-coated pit assembly

16262731



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/chr15:52194233/chr11:85722179)
- 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 TMOD3 (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 PICALM (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)
ENST00000308580TMOD3chr1552194233+ENST00000532317PICALMchr1185722179-384213052722479735
ENST00000308580TMOD3chr1552194233+ENST00000526033PICALMchr1185722179-394313052722584770
ENST00000308580TMOD3chr1552194233+ENST00000393346PICALMchr1185722179-283813052722605777
ENST00000308580TMOD3chr1552194233+ENST00000528398PICALMchr1185722179-266313052722455727
ENST00000308580TMOD3chr1552194233+ENST00000356360PICALMchr1185722179-260513052722545757
ENST00000544199TMOD3chr1552194233+ENST00000532317PICALMchr1185722179-36081071382245735
ENST00000544199TMOD3chr1552194233+ENST00000526033PICALMchr1185722179-37091071382350770
ENST00000544199TMOD3chr1552194233+ENST00000393346PICALMchr1185722179-26041071382371777
ENST00000544199TMOD3chr1552194233+ENST00000528398PICALMchr1185722179-24291071382221727
ENST00000544199TMOD3chr1552194233+ENST00000356360PICALMchr1185722179-23711071382311757

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
ENST00000308580ENST00000532317TMOD3chr1552194233+PICALMchr1185722179-0.0006662040.9993338
ENST00000308580ENST00000526033TMOD3chr1552194233+PICALMchr1185722179-0.0006229340.9993771
ENST00000308580ENST00000393346TMOD3chr1552194233+PICALMchr1185722179-0.0014368940.9985631
ENST00000308580ENST00000528398TMOD3chr1552194233+PICALMchr1185722179-0.0015522070.9984478
ENST00000308580ENST00000356360TMOD3chr1552194233+PICALMchr1185722179-0.0015648830.9984351
ENST00000544199ENST00000532317TMOD3chr1552194233+PICALMchr1185722179-0.0006640080.99933594
ENST00000544199ENST00000526033TMOD3chr1552194233+PICALMchr1185722179-0.0006311870.99936885
ENST00000544199ENST00000393346TMOD3chr1552194233+PICALMchr1185722179-0.0014934860.9985065
ENST00000544199ENST00000528398TMOD3chr1552194233+PICALMchr1185722179-0.0015631550.99843687
ENST00000544199ENST00000356360TMOD3chr1552194233+PICALMchr1185722179-0.0016981360.99830186

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 TMOD3-PICALM

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TMOD3chr1552194233PICALMchr11857221791071344TRAANAITKNNDLEKYFDMKKNQCKE
TMOD3chr1552194233PICALMchr11857221791305344TRAANAITKNNDLEKYFDMKKNQCKE

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Potential FusionNeoAntigen Information of TMOD3-PICALM 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.
TMOD3-PICALM_52194233_85722179.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)
TMOD3-PICALMchr1552194233chr11857221791305HLA-A30:08ITKNNDLEK0.97910.7859615
TMOD3-PICALMchr1552194233chr11857221791305HLA-B15:03TKNNDLEKY0.17870.84716
TMOD3-PICALMchr1552194233chr11857221791305HLA-B57:03ITKNNDLEKYF0.99970.8772617
TMOD3-PICALMchr1552194233chr11857221791305HLA-A30:01ITKNNDLEK0.97880.9036615
TMOD3-PICALMchr1552194233chr11857221791305HLA-B48:02TKNNDLEKY0.27360.9332716
TMOD3-PICALMchr1552194233chr11857221791305HLA-B15:53TKNNDLEKY0.03560.9615716
TMOD3-PICALMchr1552194233chr11857221791305HLA-B15:54TKNNDLEKY0.00930.9563716

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Potential FusionNeoAntigen Information of TMOD3-PICALM 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 TMOD3-PICALM

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
4025ITKNNDLEKYFDMKTMOD3PICALMchr1552194233chr11857221791305

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TMOD3-PICALM

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-B14:023BVN4025ITKNNDLEKYFDMK-7.9962-8.1096
HLA-B14:023BVN4025ITKNNDLEKYFDMK-5.70842-6.74372
HLA-B52:013W394025ITKNNDLEKYFDMK-6.83737-6.95077
HLA-B52:013W394025ITKNNDLEKYFDMK-4.4836-5.5189
HLA-A11:014UQ24025ITKNNDLEKYFDMK-10.0067-10.1201
HLA-A11:014UQ24025ITKNNDLEKYFDMK-9.03915-10.0745
HLA-A24:025HGA4025ITKNNDLEKYFDMK-6.56204-6.67544
HLA-A24:025HGA4025ITKNNDLEKYFDMK-5.42271-6.45801
HLA-B44:053DX84025ITKNNDLEKYFDMK-7.85648-8.89178
HLA-B44:053DX84025ITKNNDLEKYFDMK-5.3978-5.5112
HLA-A02:016TDR4025ITKNNDLEKYFDMK-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of TMOD3-PICALM

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
TMOD3-PICALMchr1552194233chr1185722179615ITKNNDLEKTAACAAAAAACAATGACTTAGAAAAAT
TMOD3-PICALMchr1552194233chr1185722179617ITKNNDLEKYFTAACAAAAAACAATGACTTAGAAAAATATTTTG
TMOD3-PICALMchr1552194233chr1185722179716TKNNDLEKYCAAAAAACAATGACTTAGAAAAATATT

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 TMOD3-PICALM

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
GBMTMOD3-PICALMchr1552194233ENST00000308580chr1185722179ENST00000356360TCGA-06-0878-01A

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Potential target of CAR-T therapy development for TMOD3-PICALM

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 TMOD3-PICALM

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 TMOD3-PICALM

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
TgenePICALMC0002395Alzheimer's Disease2CTD_human
TgenePICALMC0011265Presenile dementia2CTD_human
TgenePICALMC0276496Familial Alzheimer Disease (FAD)2CTD_human
TgenePICALMC0494463Alzheimer Disease, Late Onset2CTD_human
TgenePICALMC0546126Acute Confusional Senile Dementia2CTD_human
TgenePICALMC0750900Alzheimer's Disease, Focal Onset2CTD_human
TgenePICALMC0750901Alzheimer Disease, Early Onset2CTD_human
TgenePICALMC0234985Mental deterioration1CTD_human
TgenePICALMC0338656Impaired cognition1CTD_human
TgenePICALMC1270972Mild cognitive disorder1CTD_human