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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:CACNA1G-TATDN2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CACNA1G-TATDN2
FusionPDB ID: 12337
FusionGDB2.0 ID: 12337
HgeneTgene
Gene symbol

CACNA1G

TATDN2

Gene ID

8913

9797

Gene namecalcium voltage-gated channel subunit alpha1 GTatD DNase domain containing 2
SynonymsCa(V)T.1|Cav3.1|NBR13|SCA42|SCA42ND-
Cytomap

17q21.33

3p25.3

Type of geneprotein-codingprotein-coding
Descriptionvoltage-dependent T-type calcium channel subunit alpha-1Gcalcium channel, voltage-dependent, T type, alpha 1G subunitcav3.1cvoltage-dependent T-type calcium channel alpha 1G subunitvoltage-dependent calcium channel alpha 1G subunitvoltage-gated calciputative deoxyribonuclease TATDN2
Modification date2020031320200313
UniProtAcc

O43497

Main function of 5'-partner protein: FUNCTION: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group and are strongly blocked by mibefradil. A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. {ECO:0000269|PubMed:10648811, ECO:0000269|PubMed:10692398, ECO:0000269|PubMed:26456284, ECO:0000269|PubMed:26715324, ECO:0000269|PubMed:29878067}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000352832, ENST00000354983, 
ENST00000359106, ENST00000360761, 
ENST00000429973, ENST00000442258, 
ENST00000502264, ENST00000503485, 
ENST00000507336, ENST00000507510, 
ENST00000507609, ENST00000510115, 
ENST00000510366, ENST00000512389, 
ENST00000513689, ENST00000513964, 
ENST00000514079, ENST00000514181, 
ENST00000514717, ENST00000515165, 
ENST00000515411, ENST00000515765, 
ENST00000358244, ENST00000416767, 
ENST00000505165, ENST00000507896, 
ENST00000496355, ENST00000287652, 
ENST00000448281, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 4=1685 X 5 X 3=75
# samples 66
** MAII scorelog2(6/168*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/75*10)=-0.321928094887362
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CACNA1G [Title/Abstract] AND TATDN2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CACNA1G [Title/Abstract] AND TATDN2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CACNA1G(48703610)-TATDN2(10302170), # samples:1
Anticipated loss of major functional domain due to fusion event.CACNA1G-TATDN2 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.
CACNA1G-TATDN2 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.
CACNA1G-TATDN2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
CACNA1G-TATDN2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted 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
HgeneCACNA1G

GO:0042391

regulation of membrane potential

21084288

HgeneCACNA1G

GO:0070509

calcium ion import

21084288

HgeneCACNA1G

GO:0070588

calcium ion transmembrane transport

26456284|26715324



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/chr17:48703610/chr3:10302170)
- 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 CACNA1G (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 TATDN2 (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)
ENST00000352832CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-11142761529765482083
ENST00000352832CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-11173761529765482083
ENST00000502264CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-102156688063442114
ENST00000502264CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-102466688063442114
ENST00000515411CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-102546727063682122
ENST00000515411CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-102856727063682122
ENST00000510115CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-102066679063202106
ENST00000510115CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-102376679063202106
ENST00000503485CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-100626535061762058
ENST00000503485CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-100936535061762058
ENST00000515165CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-101646637062782092
ENST00000515165CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-101956637062782092
ENST00000507510CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-103086781064222140
ENST00000507510CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-103396781064222140
ENST00000514181CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-100896562062032067
ENST00000514181CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-101206562062032067
ENST00000515765CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-102756748063892129
ENST00000515765CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-103066748063892129
ENST00000507336CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-104106883065242174
ENST00000507336CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-104416883065242174
ENST00000514079CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-101856658062992099
ENST00000514079CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-102166658062992099
ENST00000512389CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-101316604062452081
ENST00000512389CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-101626604062452081
ENST00000513689CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-101736646062872095
ENST00000513689CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-102046646062872095
ENST00000513964CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-100296502061432047
ENST00000513964CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-100606502061432047
ENST00000507609CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-101436616062572085
ENST00000507609CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-101746616062572085
ENST00000514717CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-99936466061072035
ENST00000514717CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-100246466061072035
ENST00000510366CACNA1Gchr1748703610-ENST00000287652TATDN2chr310302170-100086481061222040
ENST00000510366CACNA1Gchr1748703610-ENST00000448281TATDN2chr310302170-100396481061222040

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
ENST00000352832ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.002154080.9978459
ENST00000352832ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0021189530.997881
ENST00000502264ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0020918010.99790823
ENST00000502264ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0020602490.99793977
ENST00000515411ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0011485710.9988514
ENST00000515411ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0011299340.9988701
ENST00000510115ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0016387490.9983613
ENST00000510115ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0016101330.99838984
ENST00000503485ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0019023010.9980977
ENST00000503485ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0018683630.9981317
ENST00000515165ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0020784590.9979215
ENST00000515165ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0020419430.99795806
ENST00000507510ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0017583820.99824166
ENST00000507510ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0017277880.9982722
ENST00000514181ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0013012050.9986987
ENST00000514181ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0012798950.99872017
ENST00000515765ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0016577010.9983423
ENST00000515765ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0016289090.99837106
ENST00000507336ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0023233370.9976767
ENST00000507336ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0022899870.99771
ENST00000514079ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0014163810.9985837
ENST00000514079ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0013932220.99860686
ENST00000512389ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0015803340.99841964
ENST00000512389ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0015533030.99844676
ENST00000513689ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0013525180.9986475
ENST00000513689ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0013307910.99866927
ENST00000513964ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0012016010.9987984
ENST00000513964ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0011812350.9988187
ENST00000507609ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0014751310.99852484
ENST00000507609ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0014510610.9985489
ENST00000514717ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0018803410.99811965
ENST00000514717ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0018466110.9981534
ENST00000510366ENST00000287652CACNA1Gchr1748703610-TATDN2chr310302170-0.0018351490.99816483
ENST00000510366ENST00000448281CACNA1Gchr1748703610-TATDN2chr310302170-0.0018022840.99819773

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 CACNA1G-TATDN2

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

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Potential FusionNeoAntigen Information of CACNA1G-TATDN2 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.

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)

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Potential FusionNeoAntigen Information of CACNA1G-TATDN2 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 CACNA1G-TATDN2

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CACNA1G-TATDN2

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

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Vaccine Design for the FusionNeoAntigens of CACNA1G-TATDN2

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

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 CACNA1G-TATDN2

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

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Potential target of CAR-T therapy development for CACNA1G-TATDN2

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 CACNA1G-TATDN2

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 CACNA1G-TATDN2

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