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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:MYH10-CDKN2A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MYH10-CDKN2A
FusionPDB ID: 56273
FusionGDB2.0 ID: 56273
HgeneTgene
Gene symbol

MYH10

CDKN2A

Gene ID

4628

1029

Gene namemyosin heavy chain 10cyclin dependent kinase inhibitor 2A
SynonymsNMMHC-IIB|NMMHCBARF|CDK4I|CDKN2|CMM2|INK4|INK4A|MLM|MTS-1|MTS1|P14|P14ARF|P16|P16-INK4A|P16INK4|P16INK4A|P19|P19ARF|TP16
Cytomap

17p13.1

9p21.3

Type of geneprotein-codingprotein-coding
Descriptionmyosin-10cellular myosin heavy chain, type Bmyosin heavy chain, nonmuscle type Bmyosin, heavy chain 10, non-musclemyosin, heavy polypeptide 10, non-musclenonmuscle myosin II heavy chain-Bnonmuscle myosin heavy chain IIBcyclin-dependent kinase inhibitor 2ACDK4 inhibitor p16-INK4alternative reading framecell cycle negative regulator betacyclin-dependent kinase 4 inhibitor Acyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)multiple tumor suppressor 1
Modification date2020031320200329
UniProtAcc

P35580

Main function of 5'-partner protein: FUNCTION: Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. During cell spreading, plays an important role in cytoskeleton reorganization, focal contacts formation (in the central part but not the margins of spreading cells), and lamellipodial extension; this function is mechanically antagonized by MYH9. {ECO:0000269|PubMed:20052411, ECO:0000269|PubMed:20603131}.

Q96HQ2

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000269243, ENST00000360416, 
ENST00000379980, ENST00000396239, 
ENST00000446177, ENST00000479692, 
ENST00000494262, ENST00000497750, 
ENST00000498124, ENST00000498628, 
ENST00000530628, ENST00000578845, 
ENST00000470819, ENST00000304494, 
ENST00000579122, ENST00000361570, 
ENST00000579755, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 15 X 5=90013 X 5 X 10=650
# samples 1516
** MAII scorelog2(15/900*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/650*10)=-2.02236781302845
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MYH10 [Title/Abstract] AND CDKN2A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MYH10 [Title/Abstract] AND CDKN2A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CDKN2A(21994138)-MYH10(8508300), # samples:2
MYH10(8526220)-CDKN2A(21971207), # samples:2
Anticipated loss of major functional domain due to fusion event.CDKN2A-MYH10 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.
CDKN2A-MYH10 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.
MYH10-CDKN2A 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.
MYH10-CDKN2A 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.
MYH10-CDKN2A 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.
MYH10-CDKN2A 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.
MYH10-CDKN2A seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
MYH10-CDKN2A seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
HgeneMYH10

GO:0000281

mitotic cytokinesis

15774463

HgeneMYH10

GO:0030048

actin filament-based movement

15845534

TgeneCDKN2A

GO:0000082

G1/S transition of mitotic cell cycle

10208428

TgeneCDKN2A

GO:0007050

cell cycle arrest

15149599

TgeneCDKN2A

GO:0008285

negative regulation of cell proliferation

15149599

TgeneCDKN2A

GO:0030308

negative regulation of cell growth

10208428

TgeneCDKN2A

GO:0032088

negative regulation of NF-kappaB transcription factor activity

10353611

TgeneCDKN2A

GO:0042326

negative regulation of phosphorylation

8259215|10208428

TgeneCDKN2A

GO:0045736

negative regulation of cyclin-dependent protein serine/threonine kinase activity

7739547|8259215



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/chr17:21994138/chr9:8508300)
- 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 MYH10 (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 CDKN2A (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)
ENST00000360416MYH10chr178526220-ENST00000361570CDKN2Achr921971207-1282484139804221
ENST00000360416MYH10chr178526220-ENST00000579755CDKN2Achr921971207-1281484139804221
ENST00000379980MYH10chr178526220-ENST00000361570CDKN2Achr921971207-123944196761221
ENST00000379980MYH10chr178526220-ENST00000579755CDKN2Achr921971207-123844196761221
ENST00000396239MYH10chr178526220-ENST00000361570CDKN2Achr921971207-123944196761221
ENST00000396239MYH10chr178526220-ENST00000579755CDKN2Achr921971207-123844196761221
ENST00000269243MYH10chr178526220-ENST00000361570CDKN2Achr921971207-1282484139804221
ENST00000269243MYH10chr178526220-ENST00000579755CDKN2Achr921971207-1281484139804221
ENST00000360416MYH10chr178526219-ENST00000361570CDKN2Achr921971207-1282484139804221
ENST00000360416MYH10chr178526219-ENST00000579755CDKN2Achr921971207-1281484139804221
ENST00000379980MYH10chr178526219-ENST00000361570CDKN2Achr921971207-123944196761221
ENST00000379980MYH10chr178526219-ENST00000579755CDKN2Achr921971207-123844196761221
ENST00000396239MYH10chr178526219-ENST00000361570CDKN2Achr921971207-123944196761221
ENST00000396239MYH10chr178526219-ENST00000579755CDKN2Achr921971207-123844196761221
ENST00000269243MYH10chr178526219-ENST00000361570CDKN2Achr921971207-1282484139804221
ENST00000269243MYH10chr178526219-ENST00000579755CDKN2Achr921971207-1281484139804221

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
ENST00000360416ENST00000361570MYH10chr178526220-CDKN2Achr921971207-0.0023159420.997684
ENST00000360416ENST00000579755MYH10chr178526220-CDKN2Achr921971207-0.0023075390.99769247
ENST00000379980ENST00000361570MYH10chr178526220-CDKN2Achr921971207-0.0021275340.9978725
ENST00000379980ENST00000579755MYH10chr178526220-CDKN2Achr921971207-0.0021185770.99788135
ENST00000396239ENST00000361570MYH10chr178526220-CDKN2Achr921971207-0.0021275340.9978725
ENST00000396239ENST00000579755MYH10chr178526220-CDKN2Achr921971207-0.0021185770.99788135
ENST00000269243ENST00000361570MYH10chr178526220-CDKN2Achr921971207-0.0023159420.997684
ENST00000269243ENST00000579755MYH10chr178526220-CDKN2Achr921971207-0.0023075390.99769247
ENST00000360416ENST00000361570MYH10chr178526219-CDKN2Achr921971207-0.0023159420.997684
ENST00000360416ENST00000579755MYH10chr178526219-CDKN2Achr921971207-0.0023075390.99769247
ENST00000379980ENST00000361570MYH10chr178526219-CDKN2Achr921971207-0.0021275340.9978725
ENST00000379980ENST00000579755MYH10chr178526219-CDKN2Achr921971207-0.0021185770.99788135
ENST00000396239ENST00000361570MYH10chr178526219-CDKN2Achr921971207-0.0021275340.9978725
ENST00000396239ENST00000579755MYH10chr178526219-CDKN2Achr921971207-0.0021185770.99788135
ENST00000269243ENST00000361570MYH10chr178526219-CDKN2Achr921971207-0.0023159420.997684
ENST00000269243ENST00000579755MYH10chr178526219-CDKN2Achr921971207-0.0023075390.99769247

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 MYH10-CDKN2A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MYH10chr178526219CDKN2Achr921971207441115HNLKDRYYSGLIYVMMMGSARVAELL
MYH10chr178526219CDKN2Achr921971207484115HNLKDRYYSGLIYVMMMGSARVAELL
MYH10chr178526220CDKN2Achr921971207441115HNLKDRYYSGLIYVMMMGSARVAELL
MYH10chr178526220CDKN2Achr921971207484115HNLKDRYYSGLIYVMMMGSARVAELL

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Potential FusionNeoAntigen Information of MYH10-CDKN2A 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.
MYH10-CDKN2A_8526219_21971207.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)
MYH10-CDKN2Achr178526219chr921971207484HLA-A68:08YVMMMGSAR0.98170.57761221
MYH10-CDKN2Achr178526219chr921971207484HLA-A68:05YVMMMGSAR0.9740.54141221
MYH10-CDKN2Achr178526219chr921971207484HLA-B15:18YYSGLIYVM0.40220.6328615
MYH10-CDKN2Achr178526219chr921971207484HLA-B15:21YYSGLIYVM0.63860.878615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:10YYSGLIYVM0.60850.9635615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:05YYSGLIYVM0.60650.9723615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:80YYSGLIYVM0.58160.9344615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:67YYSGLIYVM0.58160.9344615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:19YYSGLIYVM0.57540.7389615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:27YYSGLIYVM0.55430.9613615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:29YYSGLIYVM0.55010.9547615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:95YYSGLIYVM0.51640.74615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:13YYSGLIYVM0.48020.891615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:46YYSGLIYVM0.44320.854615
MYH10-CDKN2Achr178526219chr921971207484HLA-B39:12YYSGLIYVM0.3630.9572615
MYH10-CDKN2Achr178526219chr921971207484HLA-C12:16YYSGLIYVM0.34090.9681615
MYH10-CDKN2Achr178526219chr921971207484HLA-C04:14YYSGLIYVM0.31830.5909615
MYH10-CDKN2Achr178526219chr921971207484HLA-C03:67YYSGLIYVM0.65840.9797615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:17YYSGLIYVM0.58450.9775615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:02YYSGLIYVM0.58160.9344615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:22YYSGLIYVM0.53020.7752615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:01YYSGLIYVM0.51810.7188615
MYH10-CDKN2Achr178526219chr921971207484HLA-C07:04YYSGLIYVM0.47530.8293615
MYH10-CDKN2Achr178526219chr921971207484HLA-C06:02YYSGLIYVM0.39210.9947615
MYH10-CDKN2Achr178526219chr921971207484HLA-C06:17YYSGLIYVM0.39210.9947615
MYH10-CDKN2Achr178526219chr921971207484HLA-C04:04YYSGLIYVM0.34020.6671615
MYH10-CDKN2Achr178526219chr921971207484HLA-C18:01YYSGLIYVM0.23670.5892615
MYH10-CDKN2Achr178526219chr921971207484HLA-C14:02YYSGLIYVM0.22230.9534615
MYH10-CDKN2Achr178526219chr921971207484HLA-C14:03YYSGLIYVM0.22230.9534615
MYH10-CDKN2Achr178526219chr921971207484HLA-C06:08YYSGLIYVM0.21130.9879615
MYH10-CDKN2Achr178526219chr921971207484HLA-C06:06YYSGLIYVM0.12590.989615
MYH10-CDKN2Achr178526219chr921971207484HLA-C14:03RYYSGLIYVM0.82960.9501515
MYH10-CDKN2Achr178526219chr921971207484HLA-C14:02RYYSGLIYVM0.82960.9501515

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Potential FusionNeoAntigen Information of MYH10-CDKN2A 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.
MYH10-CDKN2A_8526219_21971207.msa

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)
MYH10-CDKN2Achr178526219chr921971207484DRB5-0102GLIYVMMMGSARVAE924
MYH10-CDKN2Achr178526219chr921971207484DRB5-0108NGLIYVMMMGSARVAE924

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Fusion breakpoint peptide structures of MYH10-CDKN2A

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
10877YYSGLIYVMMMGSAMYH10CDKN2Achr178526219chr921971207484

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MYH10-CDKN2A

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-B14:023BVN10877YYSGLIYVMMMGSA-7.15543-7.26883
HLA-B14:023BVN10877YYSGLIYVMMMGSA-4.77435-5.80965
HLA-B52:013W3910877YYSGLIYVMMMGSA-6.80875-6.92215
HLA-B52:013W3910877YYSGLIYVMMMGSA-4.20386-5.23916
HLA-A11:014UQ210877YYSGLIYVMMMGSA-7.5194-8.5547
HLA-A11:014UQ210877YYSGLIYVMMMGSA-6.9601-7.0735
HLA-A24:025HGA10877YYSGLIYVMMMGSA-7.52403-7.63743
HLA-A24:025HGA10877YYSGLIYVMMMGSA-5.82433-6.85963
HLA-B27:056PYJ10877YYSGLIYVMMMGSA-3.28285-4.31815
HLA-B44:053DX810877YYSGLIYVMMMGSA-5.91172-6.94702
HLA-B44:053DX810877YYSGLIYVMMMGSA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of MYH10-CDKN2A

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
MYH10-CDKN2Achr178526219chr9219712071221YVMMMGSARTATGTCATGATGATGGGCAGCGCCCGA
MYH10-CDKN2Achr178526219chr921971207515RYYSGLIYVMCGCTACTATTCAGGACTAATCTATGTCATG
MYH10-CDKN2Achr178526219chr921971207615YYSGLIYVMTACTATTCAGGACTAATCTATGTCATG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MYH10-CDKN2Achr178526219chr921971207924GLIYVMMMGSARVAEGGACTAATCTATGTCATGATGATGGGCAGCGCCCGAGTGGCGGAG

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Information of the samples that have these potential fusion neoantigens of MYH10-CDKN2A

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
SARCMYH10-CDKN2Achr178526219ENST00000269243chr921971207ENST00000361570TCGA-SI-A71P

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Potential target of CAR-T therapy development for MYH10-CDKN2A

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 MYH10-CDKN2A

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 MYH10-CDKN2A

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