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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:ABR-MYO1C

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ABR-MYO1C
FusionPDB ID: 555
FusionGDB2.0 ID: 555
HgeneTgene
Gene symbol

ABR

MYO1C

Gene ID

29

4643

Gene nameABR activator of RhoGEF and GTPasemyosin IE
SynonymsMDBFSGS6|HuncM-IC|MYO1C
Cytomap

17p13.3

15q22.2

Type of geneprotein-codingprotein-coding
Descriptionactive breakpoint cluster region-related proteinABR, RhoGEF and GTPase activating proteinactive BCR-relatedunconventional myosin-IeMYO1E variant proteinmyosin-ICunconventional myosin 1E
Modification date2020031320200313
UniProtAcc

Q15018

Main function of 5'-partner protein: FUNCTION: Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates (PubMed:19214193, PubMed:20032457, PubMed:20656690, PubMed:24075985). May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm (PubMed:20656690). Plays a role in regulating the onset of apoptosis via its role in modulating 'Lys-63'-linked ubiquitination of target proteins (By similarity). Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activities by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). Required for normal induction of p53/TP53 in response to DNA damage (PubMed:25283148). Independent of the BRISC complex, promotes interaction between USP7 and p53/TP53, and thereby promotes deubiquitination of p53/TP53, preventing its degradation and resulting in increased p53/TP53-mediated transcription regulation and p53/TP53-dependent apoptosis in response to DNA damage (PubMed:25283148). {ECO:0000250|UniProtKB:Q3TCJ1, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20032457, ECO:0000269|PubMed:20656690, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25283148}.

O00159

Main function of 5'-partner protein: FUNCTION: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes. {ECO:0000269|PubMed:24636949}.; FUNCTION: Isoform 3 is involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000291107, ENST00000302538, 
ENST00000536794, ENST00000544583, 
ENST00000574437, ENST00000543210, 
ENST00000572441, ENST00000573895, 
ENST00000361007, ENST00000545534, 
ENST00000575158, ENST00000573198, 
ENST00000359786, ENST00000438665, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 15 X 14=48309 X 9 X 6=486
# samples 3612
** MAII scorelog2(36/4830*10)=-3.74595437739346
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/486*10)=-2.01792190799726
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ABR [Title/Abstract] AND MYO1C [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ABR [Title/Abstract] AND MYO1C [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ABR(953289)-MYO1C(1387597), # samples:1
Anticipated loss of major functional domain due to fusion event.ABR-MYO1C 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.
ABR-MYO1C 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.
ABR-MYO1C 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.
ABR-MYO1C 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.
ABR-MYO1C seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
ABR-MYO1C seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor 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
HgeneABR

GO:0090630

activation of GTPase activity

7479768



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/chr17:953289/chr17:1387597)
- 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 ABR (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 MYO1C (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)
ENST00000302538ABRchr17953289-ENST00000359786MYO1Cchr171387597-6683193814750541635
ENST00000302538ABRchr17953289-ENST00000438665MYO1Cchr171387597-6595193814750541635
ENST00000574437ABRchr17953289-ENST00000359786MYO1Cchr171387597-6863211812352341703
ENST00000574437ABRchr17953289-ENST00000438665MYO1Cchr171387597-6775211812352341703
ENST00000291107ABRchr17953289-ENST00000359786MYO1Cchr171387597-645717123248281598
ENST00000291107ABRchr17953289-ENST00000438665MYO1Cchr171387597-636917123248281598
ENST00000536794ABRchr17953289-ENST00000359786MYO1Cchr171387597-6169142414045401466
ENST00000536794ABRchr17953289-ENST00000438665MYO1Cchr171387597-6081142414045401466

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
ENST00000302538ENST00000359786ABRchr17953289-MYO1Cchr171387597-0.0036340990.9963659
ENST00000302538ENST00000438665ABRchr17953289-MYO1Cchr171387597-0.0037302420.9962697
ENST00000574437ENST00000359786ABRchr17953289-MYO1Cchr171387597-0.004152640.9958474
ENST00000574437ENST00000438665ABRchr17953289-MYO1Cchr171387597-0.0042647790.99573517
ENST00000291107ENST00000359786ABRchr17953289-MYO1Cchr171387597-0.0032092980.9967907
ENST00000291107ENST00000438665ABRchr17953289-MYO1Cchr171387597-0.003295710.9967043
ENST00000536794ENST00000359786ABRchr17953289-MYO1Cchr171387597-0.0048008990.99519914
ENST00000536794ENST00000438665ABRchr17953289-MYO1Cchr171387597-0.0049369620.995063

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 ABR-MYO1C

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ABRchr17953289MYO1Cchr1713875971424427NEIVDKIMGKGQIQALGSDGVRVTME
ABRchr17953289MYO1Cchr1713875971712559NEIVDKIMGKGQIQALGSDGVRVTME
ABRchr17953289MYO1Cchr1713875971938596NEIVDKIMGKGQIQALGSDGVRVTME
ABRchr17953289MYO1Cchr1713875972118664NEIVDKIMGKGQIQALGSDGVRVTME

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Potential FusionNeoAntigen Information of ABR-MYO1C 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.
ABR-MYO1C_953289_1387597.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)
ABR-MYO1Cchr17953289chr1713875971712HLA-B14:01MGKGQIQAL0.98870.8191716
ABR-MYO1Cchr17953289chr1713875971712HLA-B14:02MGKGQIQAL0.98870.8191716
ABR-MYO1Cchr17953289chr1713875971712HLA-B08:01MGKGQIQAL0.97570.6293716
ABR-MYO1Cchr17953289chr1713875971712HLA-B08:09MGKGQIQAL0.93130.7297716
ABR-MYO1Cchr17953289chr1713875971712HLA-C12:12MGKGQIQAL0.9980.8628716
ABR-MYO1Cchr17953289chr1713875971712HLA-B42:02MGKGQIQAL0.98930.63716
ABR-MYO1Cchr17953289chr1713875971712HLA-B14:03MGKGQIQAL0.96840.8166716
ABR-MYO1Cchr17953289chr1713875971712HLA-C03:05MGKGQIQAL0.99890.8246716
ABR-MYO1Cchr17953289chr1713875971712HLA-C03:17MGKGQIQAL0.99870.9267716
ABR-MYO1Cchr17953289chr1713875971712HLA-C03:67MGKGQIQAL0.99850.9544716
ABR-MYO1Cchr17953289chr1713875971712HLA-C12:03MGKGQIQAL0.99830.9602716
ABR-MYO1Cchr17953289chr1713875971712HLA-C16:04MGKGQIQAL0.98780.9671716
ABR-MYO1Cchr17953289chr1713875971712HLA-B08:18MGKGQIQAL0.97570.6293716
ABR-MYO1Cchr17953289chr1713875971712HLA-B08:12MGKGQIQAL0.96170.7296716
ABR-MYO1Cchr17953289chr1713875971712HLA-C16:01MGKGQIQAL0.94830.9634716

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Potential FusionNeoAntigen Information of ABR-MYO1C 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.
ABR-MYO1C_953289_1387597.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)
ABR-MYO1Cchr17953289chr1713875971712DRB1-0102KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-0102GKGQIQALGSDGVRV823
ABR-MYO1Cchr17953289chr1713875971712DRB1-0123KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-0123GKGQIQALGSDGVRV823
ABR-MYO1Cchr17953289chr1713875971712DRB1-0804VDKIMGKGQIQALGS318
ABR-MYO1Cchr17953289chr1713875971712DRB1-0828VDKIMGKGQIQALGS318
ABR-MYO1Cchr17953289chr1713875971712DRB1-1002KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1167VDKIMGKGQIQALGS318
ABR-MYO1Cchr17953289chr1713875971712DRB1-1201KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1203KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1205KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1206KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1207KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1208KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1210KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1211KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1212KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1212GKGQIQALGSDGVRV823
ABR-MYO1Cchr17953289chr1713875971712DRB1-1213KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1213GKGQIQALGSDGVRV823
ABR-MYO1Cchr17953289chr1713875971712DRB1-1214KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1215KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1215GKGQIQALGSDGVRV823
ABR-MYO1Cchr17953289chr1713875971712DRB1-1217KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1218KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1218GKGQIQALGSDGVRV823
ABR-MYO1Cchr17953289chr1713875971712DRB1-1219KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1219GKGQIQALGSDGVRV823
ABR-MYO1Cchr17953289chr1713875971712DRB1-1220KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1220GKGQIQALGSDGVRV823
ABR-MYO1Cchr17953289chr1713875971712DRB1-1221KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1221GKGQIQALGSDGVRV823
ABR-MYO1Cchr17953289chr1713875971712DRB1-1221MGKGQIQALGSDGVR722
ABR-MYO1Cchr17953289chr1713875971712DRB1-1223KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1223GKGQIQALGSDGVRV823
ABR-MYO1Cchr17953289chr1713875971712DRB1-1410KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1415VDKIMGKGQIQALGS318
ABR-MYO1Cchr17953289chr1713875971712DRB1-1615KGQIQALGSDGVRVT924
ABR-MYO1Cchr17953289chr1713875971712DRB1-1615GKGQIQALGSDGVRV823

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Fusion breakpoint peptide structures of ABR-MYO1C

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
3832IMGKGQIQALGSDGABRMYO1Cchr17953289chr1713875971712

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ABR-MYO1C

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-B14:023BVN3832IMGKGQIQALGSDG-7.9962-8.1096
HLA-B14:023BVN3832IMGKGQIQALGSDG-5.70842-6.74372
HLA-B52:013W393832IMGKGQIQALGSDG-6.83737-6.95077
HLA-B52:013W393832IMGKGQIQALGSDG-4.4836-5.5189
HLA-A11:014UQ23832IMGKGQIQALGSDG-10.0067-10.1201
HLA-A11:014UQ23832IMGKGQIQALGSDG-9.03915-10.0745
HLA-A24:025HGA3832IMGKGQIQALGSDG-6.56204-6.67544
HLA-A24:025HGA3832IMGKGQIQALGSDG-5.42271-6.45801
HLA-B44:053DX83832IMGKGQIQALGSDG-7.85648-8.89178
HLA-B44:053DX83832IMGKGQIQALGSDG-5.3978-5.5112
HLA-A02:016TDR3832IMGKGQIQALGSDG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ABR-MYO1C

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
ABR-MYO1Cchr17953289chr171387597716MGKGQIQALGGCAAAGGACAGATCCAGGCCCTGGGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ABR-MYO1Cchr17953289chr171387597318VDKIMGKGQIQALGSGACAAGATCATGGGCAAAGGACAGATCCAGGCCCTGGGCAGTGAC
ABR-MYO1Cchr17953289chr171387597722MGKGQIQALGSDGVRGGCAAAGGACAGATCCAGGCCCTGGGCAGTGACGGGGTTCGGGTG
ABR-MYO1Cchr17953289chr171387597823GKGQIQALGSDGVRVAAAGGACAGATCCAGGCCCTGGGCAGTGACGGGGTTCGGGTGACC
ABR-MYO1Cchr17953289chr171387597924KGQIQALGSDGVRVTGGACAGATCCAGGCCCTGGGCAGTGACGGGGTTCGGGTGACCATG

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Information of the samples that have these potential fusion neoantigens of ABR-MYO1C

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
STADABR-MYO1Cchr17953289ENST00000291107chr171387597ENST00000359786TCGA-VQ-A925

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Potential target of CAR-T therapy development for ABR-MYO1C

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 ABR-MYO1C

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 ABR-MYO1C

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