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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:SPG7-MOB1A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SPG7-MOB1A
FusionPDB ID: 85761
FusionGDB2.0 ID: 85761
HgeneTgene
Gene symbol

SPG7

MOB1A

Gene ID

6687

55233

Gene nameSPG7 matrix AAA peptidase subunit, parapleginMOB kinase activator 1A
SynonymsCAR|CMAR|PGN|SPG5CC2orf6|MATS1|MOB1|MOBK1B|MOBKL1B|Mob4B
Cytomap

16q24.3

2p13.1

Type of geneprotein-codingprotein-coding
DescriptionparapleginSPG7, paraplegin matrix AAA peptidase subunitcell matrix adhesion regulatorspastic paraplegia 7 (pure and complicated autosomal recessive)spastic paraplegia 7 proteinMOB kinase activator 1AMOB1 Mps One Binder homolog AMOB1, Mps One Binder kinase activator-like 1Bmob1 alphamob1 homolog 1Bmps one binder kinase activator-like 1B
Modification date2020032020200313
UniProtAcc.

Q9H8S9

Main function of 5'-partner protein: FUNCTION: Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38 and STK38L. Acts cooperatively with STK3/MST2 to activate STK38. {ECO:0000269|PubMed:15197186, ECO:0000269|PubMed:18362890, ECO:0000269|PubMed:19739119}.
Ensembl transtripts involved in fusion geneENST idsENST00000268704, ENST00000341316, 
ENST00000565891, 
ENST00000409969, 
ENST00000497054, ENST00000396049, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 7 X 6=4206 X 6 X 4=144
# samples 106
** MAII scorelog2(10/420*10)=-2.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/144*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SPG7 [Title/Abstract] AND MOB1A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SPG7 [Title/Abstract] AND MOB1A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SPG7(89579445)-MOB1A(74394234), # samples:1
Anticipated loss of major functional domain due to fusion event.SPG7-MOB1A 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.
SPG7-MOB1A 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
TgeneMOB1A

GO:0035329

hippo signaling

19739119



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/chr16:89579445/chr2:74394234)
- 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 SPG7 (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 MOB1A (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)
ENST00000268704SPG7chr1689579445+ENST00000396049MOB1Achr274394234-490139115860281
ENST00000341316SPG7chr1689579445+ENST00000396049MOB1Achr274394234-48933837852281

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
ENST00000268704ENST00000396049SPG7chr1689579445+MOB1Achr274394234-0.0003548640.9996451
ENST00000341316ENST00000396049SPG7chr1689579445+MOB1Achr274394234-0.0003521780.99964786

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 SPG7-MOB1A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SPG7chr1689579445MOB1Achr274394234383125KDKSKGKAPEEDEAVDFFNQINMLYG
SPG7chr1689579445MOB1Achr274394234391125KDKSKGKAPEEDEAVDFFNQINMLYG

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Potential FusionNeoAntigen Information of SPG7-MOB1A 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.
SPG7-MOB1A_89579445_74394234.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)
SPG7-MOB1Achr1689579445chr274394234391HLA-B52:01EAVDFFNQI0.98690.81891221
SPG7-MOB1Achr1689579445chr274394234391HLA-B44:03EEDEAVDFF0.97890.8843918
SPG7-MOB1Achr1689579445chr274394234391HLA-B18:01EEDEAVDFF0.8590.9654918
SPG7-MOB1Achr1689579445chr274394234391HLA-B35:08APEEDEAVDF0.93640.9536717
SPG7-MOB1Achr1689579445chr274394234391HLA-B35:08APEEDEAVDFF0.99360.9488718
SPG7-MOB1Achr1689579445chr274394234391HLA-B51:07EAVDFFNQI0.99010.77351221
SPG7-MOB1Achr1689579445chr274394234391HLA-C06:03EAVDFFNQI0.7870.99361221
SPG7-MOB1Achr1689579445chr274394234391HLA-C01:17KAPEEDEAV0.54670.9124615
SPG7-MOB1Achr1689579445chr274394234391HLA-B39:08EEDEAVDFF0.1140.656918
SPG7-MOB1Achr1689579445chr274394234391HLA-B51:07DEAVDFFNQI0.72910.76991121
SPG7-MOB1Achr1689579445chr274394234391HLA-A25:01EAVDFFNQI0.99640.73321221
SPG7-MOB1Achr1689579445chr274394234391HLA-B44:13EEDEAVDFF0.97890.8843918
SPG7-MOB1Achr1689579445chr274394234391HLA-B44:07EEDEAVDFF0.97890.8843918
SPG7-MOB1Achr1689579445chr274394234391HLA-B44:26EEDEAVDFF0.97890.8843918
SPG7-MOB1Achr1689579445chr274394234391HLA-B18:04EEDEAVDFF0.91350.9689918
SPG7-MOB1Achr1689579445chr274394234391HLA-C16:04EAVDFFNQI0.90740.97631221
SPG7-MOB1Achr1689579445chr274394234391HLA-B18:07EEDEAVDFF0.87530.9545918
SPG7-MOB1Achr1689579445chr274394234391HLA-B18:06EEDEAVDFF0.87140.969918
SPG7-MOB1Achr1689579445chr274394234391HLA-B18:05EEDEAVDFF0.8590.9654918
SPG7-MOB1Achr1689579445chr274394234391HLA-B18:08EEDEAVDFF0.8450.8883918
SPG7-MOB1Achr1689579445chr274394234391HLA-B18:03EEDEAVDFF0.76430.9631918
SPG7-MOB1Achr1689579445chr274394234391HLA-B18:11EEDEAVDFF0.75530.8912918
SPG7-MOB1Achr1689579445chr274394234391HLA-C01:03KAPEEDEAV0.72680.9329615
SPG7-MOB1Achr1689579445chr274394234391HLA-C12:03EAVDFFNQI0.68950.97511221
SPG7-MOB1Achr1689579445chr274394234391HLA-C01:02KAPEEDEAV0.52960.9129615

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Potential FusionNeoAntigen Information of SPG7-MOB1A 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 SPG7-MOB1A

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
4119KAPEEDEAVDFFNQSPG7MOB1Achr1689579445chr274394234391

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SPG7-MOB1A

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-B14:023BVN4119KAPEEDEAVDFFNQ-7.36978-7.48318
HLA-B14:023BVN4119KAPEEDEAVDFFNQ-4.19173-5.22703
HLA-B52:013W394119KAPEEDEAVDFFNQ-6.08078-7.11608
HLA-B52:013W394119KAPEEDEAVDFFNQ-6.02808-6.14148
HLA-A11:014UQ24119KAPEEDEAVDFFNQ-11.396-11.5094
HLA-A24:025HGA4119KAPEEDEAVDFFNQ-5.5142-6.5495
HLA-A24:025HGA4119KAPEEDEAVDFFNQ-5.43263-5.54603
HLA-B27:056PYJ4119KAPEEDEAVDFFNQ-5.93836-6.05176
HLA-B44:053DX84119KAPEEDEAVDFFNQ-5.39102-5.50442
HLA-B44:053DX84119KAPEEDEAVDFFNQ-4.5657-5.601

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Vaccine Design for the FusionNeoAntigens of SPG7-MOB1A

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
SPG7-MOB1Achr1689579445chr2743942341121DEAVDFFNQIACGAAGCTGTGGATTTCTTTAACCAGATCA
SPG7-MOB1Achr1689579445chr2743942341221EAVDFFNQIAAGCTGTGGATTTCTTTAACCAGATCA
SPG7-MOB1Achr1689579445chr274394234615KAPEEDEAVAGGCGCCTGAAGAGGACGAAGCTGTGG
SPG7-MOB1Achr1689579445chr274394234717APEEDEAVDFCGCCTGAAGAGGACGAAGCTGTGGATTTCT
SPG7-MOB1Achr1689579445chr274394234718APEEDEAVDFFCGCCTGAAGAGGACGAAGCTGTGGATTTCTTTA
SPG7-MOB1Achr1689579445chr274394234918EEDEAVDFFAAGAGGACGAAGCTGTGGATTTCTTTA

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 SPG7-MOB1A

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
STADSPG7-MOB1Achr1689579445ENST00000268704chr274394234ENST00000396049TCGA-HU-A4GN-01A

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Potential target of CAR-T therapy development for SPG7-MOB1A

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 SPG7-MOB1A

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 SPG7-MOB1A

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