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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:MIDN-ABCA7

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MIDN-ABCA7
FusionPDB ID: 53600
FusionGDB2.0 ID: 53600
HgeneTgene
Gene symbol

MIDN

ABCA7

Gene ID

90007

10347

Gene namemidnolinATP binding cassette subfamily A member 7
Synonyms-ABCA-SSN|ABCX|AD9
Cytomap

19p13.3

19p13.3

Type of geneprotein-codingprotein-coding
Descriptionmidnolinmidbrain nucleolar proteinphospholipid-transporting ATPase ABCA7ATP-binding cassette sub-family A member 7ATP-binding cassette, sub-family A (ABC1), member 7autoantigen SS-Nmacrophage ABC transporter
Modification date2020031320200320
UniProtAcc

Q504T8

Main function of 5'-partner protein: FUNCTION: Facilitates ubiquitin-independent proteasomal degradation of polycomb protein CBX4. Plays a role in inhibiting the activity of glucokinase GCK and both glucose-induced and basal insulin secretion. {ECO:0000250|UniProtKB:D4AE48, ECO:0000250|UniProtKB:Q3TPJ7}.

Q8IZY2

Main function of 5'-partner protein: FUNCTION: Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Transports preferentially phosphatidylserine over phosphatidylcholine (PubMed:24097981). Plays a role in lipid homeostasis and macrophage-mediated phagocytosis (PubMed:14592415, PubMed:12917409, PubMed:12925201, PubMed:14570867). Binds APOA1 and may function in apolipoprotein-mediated phospholipid efflux from cells (PubMed:12917409, PubMed:14570867, PubMed:14592415). May also mediate cholesterol efflux (PubMed:14570867). May regulate cellular ceramide homeostasis during keratinocyte differentiation (PubMed:12925201). Involved in lipid raft organization and CD1D localization on thymocytes and antigen-presenting cells, which plays an important role in natural killer T-cell development and activation (By similarity). Plays a role in phagocytosis of apoptotic cells by macrophages (By similarity). Macrophage phagocytosis is stimulated by APOA1 or APOA2, probably by stabilization of ABCA7 (By similarity). Also involved in phagocytic clearance of amyloid-beta by microglia cells and macrophages (By similarity). Further limits amyloid-beta production by playing a role in the regulation of amyloid-beta A4 precursor protein (APP) endocytosis and/or processing (PubMed:26260791). Amyloid-beta is the main component of amyloid plaques found in the brains of Alzheimer patients (PubMed:26260791). {ECO:0000250|UniProtKB:Q91V24, ECO:0000269|PubMed:12917409, ECO:0000269|PubMed:12925201, ECO:0000269|PubMed:14570867, ECO:0000269|PubMed:14592415, ECO:0000269|PubMed:24097981, ECO:0000269|PubMed:26260791}.
Ensembl transtripts involved in fusion geneENST idsENST00000300952, ENST00000591446, 
ENST00000533574, ENST00000263094, 
ENST00000433129, ENST00000435683, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 7 X 6=3785 X 4 X 4=80
# samples 135
** MAII scorelog2(13/378*10)=-1.53987461119262
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MIDN [Title/Abstract] AND ABCA7 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MIDN [Title/Abstract] AND ABCA7 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MIDN(1251900)-ABCA7(1061781), # samples:2
Anticipated loss of major functional domain due to fusion event.MIDN-ABCA7 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.
MIDN-ABCA7 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.
MIDN-ABCA7 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.
MIDN-ABCA7 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
TgeneABCA7

GO:0033344

cholesterol efflux

14570867

TgeneABCA7

GO:0033700

phospholipid efflux

14570867

TgeneABCA7

GO:0034380

high-density lipoprotein particle assembly

14570867

TgeneABCA7

GO:0038027

apolipoprotein A-I-mediated signaling pathway

14570867

TgeneABCA7

GO:0045332

phospholipid translocation

24097981



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/chr19:1251900/chr19:1061781)
- 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 MIDN (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 ABCA7 (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)
ENST00000300952MIDNchr191251900+ENST00000263094ABCA7chr191061781+20218993411876511
ENST00000300952MIDNchr191251900+ENST00000433129ABCA7chr191061781+20218993411876511
ENST00000300952MIDNchr191251900+ENST00000435683ABCA7chr191061781+18778993411876512
ENST00000591446MIDNchr191251900+ENST00000263094ABCA7chr191061781+19157932351770511
ENST00000591446MIDNchr191251900+ENST00000433129ABCA7chr191061781+19157932351770511
ENST00000591446MIDNchr191251900+ENST00000435683ABCA7chr191061781+17717932351770512

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
ENST00000300952ENST00000263094MIDNchr191251900+ABCA7chr191061781+0.0698524340.9301475
ENST00000300952ENST00000433129MIDNchr191251900+ABCA7chr191061781+0.0698524340.9301475
ENST00000300952ENST00000435683MIDNchr191251900+ABCA7chr191061781+0.0602966440.9397034
ENST00000591446ENST00000263094MIDNchr191251900+ABCA7chr191061781+0.074107270.92589265
ENST00000591446ENST00000433129MIDNchr191251900+ABCA7chr191061781+0.074107270.92589265
ENST00000591446ENST00000435683MIDNchr191251900+ABCA7chr191061781+0.064531840.9354682

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 MIDN-ABCA7

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MIDNchr191251900ABCA7chr19106178179324FLEEDARCSAPPSARRTRHPGSLSPL
MIDNchr191251900ABCA7chr19106178189924FLEEDARCSAPPSARRTRHPGSLSPL

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Potential FusionNeoAntigen Information of MIDN-ABCA7 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.
MIDN-ABCA7_1251900_1061781.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)
MIDN-ABCA7chr191251900chr191061781899HLA-A68:24CSAPPSARR0.99750.566716
MIDN-ABCA7chr191251900chr191061781899HLA-A68:03CSAPPSARR0.99570.5462716
MIDN-ABCA7chr191251900chr191061781899HLA-A11:10CSAPPSARR0.99290.5197716
MIDN-ABCA7chr191251900chr191061781899HLA-A66:01CSAPPSARR0.99160.62716
MIDN-ABCA7chr191251900chr191061781899HLA-A68:08CSAPPSARR0.98850.5732716
MIDN-ABCA7chr191251900chr191061781899HLA-A68:06CSAPPSARR0.98470.5857716
MIDN-ABCA7chr191251900chr191061781899HLA-B39:06ARCSAPPSA0.9840.8515514
MIDN-ABCA7chr191251900chr191061781899HLA-A74:03CSAPPSARR0.97790.8836716
MIDN-ABCA7chr191251900chr191061781899HLA-A74:11CSAPPSARR0.97790.8836716
MIDN-ABCA7chr191251900chr191061781899HLA-A74:09CSAPPSARR0.97790.8836716
MIDN-ABCA7chr191251900chr191061781899HLA-A31:06CSAPPSARR0.97750.7186716
MIDN-ABCA7chr191251900chr191061781899HLA-A68:05CSAPPSARR0.97680.5732716
MIDN-ABCA7chr191251900chr191061781899HLA-A34:05CSAPPSARR0.97280.6176716
MIDN-ABCA7chr191251900chr191061781899HLA-A34:01CSAPPSARR0.97280.6176716
MIDN-ABCA7chr191251900chr191061781899HLA-A31:02CSAPPSARR0.96830.8999716
MIDN-ABCA7chr191251900chr191061781899HLA-A34:02CSAPPSARR0.94640.5817716
MIDN-ABCA7chr191251900chr191061781899HLA-A66:03CSAPPSARR0.940.7036716
MIDN-ABCA7chr191251900chr191061781899HLA-A26:03CSAPPSARR0.82280.6665716
MIDN-ABCA7chr191251900chr191061781899HLA-A31:06RCSAPPSAR0.50470.5848615
MIDN-ABCA7chr191251900chr191061781899HLA-A74:03RCSAPPSARR0.94390.8474616
MIDN-ABCA7chr191251900chr191061781899HLA-A74:11RCSAPPSARR0.94390.8474616
MIDN-ABCA7chr191251900chr191061781899HLA-A74:09RCSAPPSARR0.94390.8474616
MIDN-ABCA7chr191251900chr191061781899HLA-A31:02RCSAPPSARR0.93160.8731616
MIDN-ABCA7chr191251900chr191061781899HLA-A31:06RCSAPPSARR0.56680.7058616
MIDN-ABCA7chr191251900chr191061781899HLA-A03:12RCSAPPSARR0.41110.5957616
MIDN-ABCA7chr191251900chr191061781899HLA-A03:25RCSAPPSARR0.38390.5699616
MIDN-ABCA7chr191251900chr191061781899HLA-A11:04RCSAPPSARR0.38330.5301616
MIDN-ABCA7chr191251900chr191061781899HLA-B27:05ARCSAPPSARR0.99910.6728516
MIDN-ABCA7chr191251900chr191061781899HLA-A33:05DARCSAPPSAR0.99830.7517415
MIDN-ABCA7chr191251900chr191061781899HLA-A33:01DARCSAPPSAR0.99830.7517415
MIDN-ABCA7chr191251900chr191061781899HLA-A68:24DARCSAPPSAR0.99650.8006415
MIDN-ABCA7chr191251900chr191061781899HLA-A68:03DARCSAPPSAR0.99530.7869415
MIDN-ABCA7chr191251900chr191061781899HLA-A68:05DARCSAPPSAR0.98520.7894415
MIDN-ABCA7chr191251900chr191061781899HLA-A31:06ARCSAPPSARR0.930.7005516
MIDN-ABCA7chr191251900chr191061781899HLA-A68:01CSAPPSARR0.99750.566716
MIDN-ABCA7chr191251900chr191061781899HLA-B27:14ARCSAPPSA0.99630.7817514
MIDN-ABCA7chr191251900chr191061781899HLA-A31:01CSAPPSARR0.9840.8634716
MIDN-ABCA7chr191251900chr191061781899HLA-B73:01ARCSAPPSA0.9810.8645514
MIDN-ABCA7chr191251900chr191061781899HLA-A31:01RCSAPPSAR0.92970.7767615
MIDN-ABCA7chr191251900chr191061781899HLA-A31:01RCSAPPSARR0.95670.8261616
MIDN-ABCA7chr191251900chr191061781899HLA-B73:01DARCSAPPSA0.87210.8627414
MIDN-ABCA7chr191251900chr191061781899HLA-A03:01RCSAPPSARR0.38390.5699616
MIDN-ABCA7chr191251900chr191061781899HLA-A68:01DARCSAPPSAR0.99650.8006415
MIDN-ABCA7chr191251900chr191061781899HLA-A31:01ARCSAPPSARR0.98790.8307516
MIDN-ABCA7chr191251900chr191061781899HLA-A11:01ARCSAPPSARR0.87020.5079516
MIDN-ABCA7chr191251900chr191061781899HLA-A74:01CSAPPSARR0.97790.8836716
MIDN-ABCA7chr191251900chr191061781899HLA-A66:02CSAPPSARR0.93980.722716
MIDN-ABCA7chr191251900chr191061781899HLA-A74:01RCSAPPSARR0.94390.8474616
MIDN-ABCA7chr191251900chr191061781899HLA-B27:10ARCSAPPSARR0.99860.8577516
MIDN-ABCA7chr191251900chr191061781899HLA-A11:02ARCSAPPSARR0.87020.5079516

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Potential FusionNeoAntigen Information of MIDN-ABCA7 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 MIDN-ABCA7

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
7724RCSAPPSARRTRHPMIDNABCA7chr191251900chr191061781899

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MIDN-ABCA7

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-B14:023BVN7724RCSAPPSARRTRHP-7.9962-8.1096
HLA-B14:023BVN7724RCSAPPSARRTRHP-5.70842-6.74372
HLA-B52:013W397724RCSAPPSARRTRHP-6.83737-6.95077
HLA-B52:013W397724RCSAPPSARRTRHP-4.4836-5.5189
HLA-A11:014UQ27724RCSAPPSARRTRHP-10.0067-10.1201
HLA-A11:014UQ27724RCSAPPSARRTRHP-9.03915-10.0745
HLA-A24:025HGA7724RCSAPPSARRTRHP-6.56204-6.67544
HLA-A24:025HGA7724RCSAPPSARRTRHP-5.42271-6.45801
HLA-B44:053DX87724RCSAPPSARRTRHP-7.85648-8.89178
HLA-B44:053DX87724RCSAPPSARRTRHP-5.3978-5.5112
HLA-A02:016TDR7724RCSAPPSARRTRHP-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of MIDN-ABCA7

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
MIDN-ABCA7chr191251900chr191061781414DARCSAPPSAGCTCTCGAGAGTCTCACGGAGACGCAGTGT
MIDN-ABCA7chr191251900chr191061781415DARCSAPPSARGCTCTCGAGAGTCTCACGGAGACGCAGTGTTTT
MIDN-ABCA7chr191251900chr191061781514ARCSAPPSACTCGAGAGTCTCACGGAGACGCAGTGT
MIDN-ABCA7chr191251900chr191061781516ARCSAPPSARRCTCGAGAGTCTCACGGAGACGCAGTGTTTTGGG
MIDN-ABCA7chr191251900chr191061781615RCSAPPSARGAGAGTCTCACGGAGACGCAGTGTTTT
MIDN-ABCA7chr191251900chr191061781616RCSAPPSARRGAGAGTCTCACGGAGACGCAGTGTTTTGGG
MIDN-ABCA7chr191251900chr191061781716CSAPPSARRAGTCTCACGGAGACGCAGTGTTTTGGG

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 MIDN-ABCA7

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
LUADMIDN-ABCA7chr191251900ENST00000300952chr191061781ENST00000263094TCGA-05-4418-01A

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Potential target of CAR-T therapy development for MIDN-ABCA7

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
TgeneABCA7chr19:1251900chr19:1061781ENST0000043568333411683_170302009.0TransmembraneHelical
TgeneABCA7chr19:1251900chr19:1061781ENST0000043568333411729_174902009.0TransmembraneHelical

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 MIDN-ABCA7

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 MIDN-ABCA7

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