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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:POLB-ASH2L

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: POLB-ASH2L
FusionPDB ID: 66887
FusionGDB2.0 ID: 66887
HgeneTgene
Gene symbol

POLB

ASH2L

Gene ID

11232

9070

Gene nameDNA polymerase gamma 2, accessory subunitASH2 like, histone lysine methyltransferase complex subunit
SynonymsHP55|MTDPS16|MTPOLB|PEOA4|POLB|POLG-BETA|POLGBASH2|ASH2L1|ASH2L2|Bre2
Cytomap

17q23.3

8p11.23

Type of geneprotein-codingprotein-coding
DescriptionDNA polymerase subunit gamma-2, mitochondrialDNA polymerase gamma accessory 55 kDa subunitmitochondrial DNA polymerase subunit gamma-2mitochondrial DNA polymerase, accessory subunitp55polymerase (DNA directed), gamma 2, accessory subunitpolymerase (set1/Ash2 histone methyltransferase complex subunit ASH2ASH2-like proteinash2 (absent, small, or homeotic)-like
Modification date2020031320200313
UniProtAcc.

Q9UBL3

Main function of 5'-partner protein: FUNCTION: Transcriptional regulator (PubMed:12670868). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated (PubMed:19556245). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (PubMed:19556245). May play a role in hematopoiesis (PubMed:12670868). In association with RBBP5 and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653). {ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22266653}.
Ensembl transtripts involved in fusion geneENST idsENST00000265421, ENST00000521492, 
ENST00000538005, ENST00000530566, 
ENST00000524263, ENST00000250635, 
ENST00000343823, ENST00000428278, 
ENST00000521652, ENST00000545394, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 3 X 4=729 X 9 X 6=486
# samples 89
** MAII scorelog2(8/72*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(9/486*10)=-2.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: POLB [Title/Abstract] AND ASH2L [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: POLB [Title/Abstract] AND ASH2L [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)POLB(42227506)-ASH2L(37976788), # samples:1
POLB(42227506)-ASH2L(37976787), # samples:1
Anticipated loss of major functional domain due to fusion event.POLB-ASH2L 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.
POLB-ASH2L 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.
POLB-ASH2L 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.
POLB-ASH2L 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
HgenePOLB

GO:0006261

DNA-dependent DNA replication

10608893|15167897|19837034|19858216|26123486|26446790|28430993

HgenePOLB

GO:1900264

positive regulation of DNA-directed DNA polymerase activity

10608893|19837034|19858216|26123486

TgeneASH2L

GO:0006974

cellular response to DNA damage stimulus

17500065

TgeneASH2L

GO:0043627

response to estrogen

16603732

TgeneASH2L

GO:0051568

histone H3-K4 methylation

17355966|19556245



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/chr8:42227506/chr8:37976788)
- 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 POLB (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 ASH2L (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)
ENST00000265421POLBchr842227506+ENST00000343823ASH2Lchr837976788+301110831702116648
ENST00000265421POLBchr842227506+ENST00000250635ASH2Lchr837976788+265410831702017615
ENST00000265421POLBchr842227506+ENST00000545394ASH2Lchr837976788+256910831702116648
ENST00000265421POLBchr842227506+ENST00000428278ASH2Lchr837976788+274910831702116648
ENST00000265421POLBchr842227506+ENST00000521652ASH2Lchr837976788+265010831702017615
ENST00000538005POLBchr842227506+ENST00000343823ASH2Lchr837976788+27308022821835517
ENST00000538005POLBchr842227506+ENST00000250635ASH2Lchr837976788+23738022821736484
ENST00000538005POLBchr842227506+ENST00000545394ASH2Lchr837976788+22888022821835517
ENST00000538005POLBchr842227506+ENST00000428278ASH2Lchr837976788+24688022821835517
ENST00000538005POLBchr842227506+ENST00000521652ASH2Lchr837976788+23698022821736484
ENST00000521492POLBchr842227506+ENST00000343823ASH2Lchr837976788+24685404011573390
ENST00000521492POLBchr842227506+ENST00000250635ASH2Lchr837976788+21115404011474357
ENST00000521492POLBchr842227506+ENST00000545394ASH2Lchr837976788+20265404011573390
ENST00000521492POLBchr842227506+ENST00000428278ASH2Lchr837976788+22065404011573390
ENST00000521492POLBchr842227506+ENST00000521652ASH2Lchr837976788+21075404011474357
ENST00000265421POLBchr842227506+ENST00000343823ASH2Lchr837976787+301110831702116648
ENST00000265421POLBchr842227506+ENST00000250635ASH2Lchr837976787+265410831702017615
ENST00000265421POLBchr842227506+ENST00000545394ASH2Lchr837976787+256910831702116648
ENST00000265421POLBchr842227506+ENST00000428278ASH2Lchr837976787+274910831702116648
ENST00000265421POLBchr842227506+ENST00000521652ASH2Lchr837976787+265010831702017615
ENST00000538005POLBchr842227506+ENST00000343823ASH2Lchr837976787+27308022821835517
ENST00000538005POLBchr842227506+ENST00000250635ASH2Lchr837976787+23738022821736484
ENST00000538005POLBchr842227506+ENST00000545394ASH2Lchr837976787+22888022821835517
ENST00000538005POLBchr842227506+ENST00000428278ASH2Lchr837976787+24688022821835517
ENST00000538005POLBchr842227506+ENST00000521652ASH2Lchr837976787+23698022821736484
ENST00000521492POLBchr842227506+ENST00000343823ASH2Lchr837976787+24685404011573390
ENST00000521492POLBchr842227506+ENST00000250635ASH2Lchr837976787+21115404011474357
ENST00000521492POLBchr842227506+ENST00000545394ASH2Lchr837976787+20265404011573390
ENST00000521492POLBchr842227506+ENST00000428278ASH2Lchr837976787+22065404011573390
ENST00000521492POLBchr842227506+ENST00000521652ASH2Lchr837976787+21075404011474357

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
ENST00000265421ENST00000343823POLBchr842227506+ASH2Lchr837976788+0.0003828430.9996171
ENST00000265421ENST00000250635POLBchr842227506+ASH2Lchr837976788+0.000440790.9995592
ENST00000265421ENST00000545394POLBchr842227506+ASH2Lchr837976788+0.0005277990.9994722
ENST00000265421ENST00000428278POLBchr842227506+ASH2Lchr837976788+0.0004017750.9995982
ENST00000265421ENST00000521652POLBchr842227506+ASH2Lchr837976788+0.0004642410.9995358
ENST00000538005ENST00000343823POLBchr842227506+ASH2Lchr837976788+0.0003529840.999647
ENST00000538005ENST00000250635POLBchr842227506+ASH2Lchr837976788+0.0004828220.9995172
ENST00000538005ENST00000545394POLBchr842227506+ASH2Lchr837976788+0.0004809560.9995191
ENST00000538005ENST00000428278POLBchr842227506+ASH2Lchr837976788+0.0003760880.9996239
ENST00000538005ENST00000521652POLBchr842227506+ASH2Lchr837976788+0.000503870.9994961
ENST00000521492ENST00000343823POLBchr842227506+ASH2Lchr837976788+0.0001489970.999851
ENST00000521492ENST00000250635POLBchr842227506+ASH2Lchr837976788+0.0002473820.9997526
ENST00000521492ENST00000545394POLBchr842227506+ASH2Lchr837976788+0.0001866570.9998134
ENST00000521492ENST00000428278POLBchr842227506+ASH2Lchr837976788+0.0001427840.9998572
ENST00000521492ENST00000521652POLBchr842227506+ASH2Lchr837976788+0.000257470.99974257
ENST00000265421ENST00000343823POLBchr842227506+ASH2Lchr837976787+0.0003828430.9996171
ENST00000265421ENST00000250635POLBchr842227506+ASH2Lchr837976787+0.000440790.9995592
ENST00000265421ENST00000545394POLBchr842227506+ASH2Lchr837976787+0.0005277990.9994722
ENST00000265421ENST00000428278POLBchr842227506+ASH2Lchr837976787+0.0004017750.9995982
ENST00000265421ENST00000521652POLBchr842227506+ASH2Lchr837976787+0.0004642410.9995358
ENST00000538005ENST00000343823POLBchr842227506+ASH2Lchr837976787+0.0003529840.999647
ENST00000538005ENST00000250635POLBchr842227506+ASH2Lchr837976787+0.0004828220.9995172
ENST00000538005ENST00000545394POLBchr842227506+ASH2Lchr837976787+0.0004809560.9995191
ENST00000538005ENST00000428278POLBchr842227506+ASH2Lchr837976787+0.0003760880.9996239
ENST00000538005ENST00000521652POLBchr842227506+ASH2Lchr837976787+0.000503870.9994961
ENST00000521492ENST00000343823POLBchr842227506+ASH2Lchr837976787+0.0001489970.999851
ENST00000521492ENST00000250635POLBchr842227506+ASH2Lchr837976787+0.0002473820.9997526
ENST00000521492ENST00000545394POLBchr842227506+ASH2Lchr837976787+0.0001866570.9998134
ENST00000521492ENST00000428278POLBchr842227506+ASH2Lchr837976787+0.0001427840.9998572
ENST00000521492ENST00000521652POLBchr842227506+ASH2Lchr837976787+0.000257470.99974257

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 POLB-ASH2L

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
POLBchr842227506ASH2Lchr8379767871083304TINEYTIRPLGVTGGIAAGSSGKGRG
POLBchr842227506ASH2Lchr83797678754046TINEYTIRPLGVTGGIAAGSSGKGRG
POLBchr842227506ASH2Lchr837976787802173TINEYTIRPLGVTGGIAAGSSGKGRG
POLBchr842227506ASH2Lchr8379767881083304TINEYTIRPLGVTGGIAAGSSGKGRG
POLBchr842227506ASH2Lchr83797678854046TINEYTIRPLGVTGGIAAGSSGKGRG
POLBchr842227506ASH2Lchr837976788802173TINEYTIRPLGVTGGIAAGSSGKGRG

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Potential FusionNeoAntigen Information of POLB-ASH2L 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.
POLB-ASH2L_42227506_37976787.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)
POLB-ASH2Lchr842227506chr8379767871083HLA-B55:01RPLGVTGGIA0.92120.5442717
POLB-ASH2Lchr842227506chr8379767871083HLA-B56:01RPLGVTGGIA0.88780.6283717
POLB-ASH2Lchr842227506chr8379767871083HLA-B55:01RPLGVTGGIAA0.99270.7145718
POLB-ASH2Lchr842227506chr8379767871083HLA-B56:01RPLGVTGGIAA0.98860.7529718
POLB-ASH2Lchr842227506chr8379767871083HLA-B54:01RPLGVTGGIAA0.99630.8841718
POLB-ASH2Lchr842227506chr8379767871083HLA-B67:01RPLGVTGGI0.30570.7261716
POLB-ASH2Lchr842227506chr8379767871083HLA-B55:02RPLGVTGGIA0.90780.637717
POLB-ASH2Lchr842227506chr8379767871083HLA-B55:02RPLGVTGGIAA0.99260.7853718
POLB-ASH2Lchr842227506chr8379767871083HLA-B56:05RPLGVTGGIAA0.90980.687718

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Potential FusionNeoAntigen Information of POLB-ASH2L 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.
POLB-ASH2L_42227506_37976787.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)
POLB-ASH2Lchr842227506chr8379767871083DRB1-0415EYTIRPLGVTGGIAA318
POLB-ASH2Lchr842227506chr8379767871083DRB1-0415NEYTIRPLGVTGGIA217
POLB-ASH2Lchr842227506chr8379767871083DRB1-0436EYTIRPLGVTGGIAA318
POLB-ASH2Lchr842227506chr8379767871083DRB1-0436NEYTIRPLGVTGGIA217
POLB-ASH2Lchr842227506chr8379767871083DRB1-0453EYTIRPLGVTGGIAA318
POLB-ASH2Lchr842227506chr8379767871083DRB1-0458EYTIRPLGVTGGIAA318

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Fusion breakpoint peptide structures of POLB-ASH2L

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
3953IRPLGVTGGIAAGSPOLBASH2Lchr842227506chr8379767871083

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of POLB-ASH2L

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-B14:023BVN3953IRPLGVTGGIAAGS-7.75776-7.86956
HLA-B14:023BVN3953IRPLGVTGGIAAGS-4.52646-5.56956
HLA-B52:013W393953IRPLGVTGGIAAGS-7.1873-7.2991
HLA-B52:013W393953IRPLGVTGGIAAGS-2.81174-3.85484
HLA-A11:014UQ23953IRPLGVTGGIAAGS-5.13576-5.24756
HLA-A24:025HGA3953IRPLGVTGGIAAGS-8.42076-8.53256
HLA-A24:025HGA3953IRPLGVTGGIAAGS-7.10496-8.14806
HLA-B27:056PYJ3953IRPLGVTGGIAAGS-9.28296-9.39476
HLA-B44:053DX83953IRPLGVTGGIAAGS-6.88262-6.99442
HLA-B44:053DX83953IRPLGVTGGIAAGS-5.46822-6.51132

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Vaccine Design for the FusionNeoAntigens of POLB-ASH2L

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
POLB-ASH2Lchr842227506chr837976787716RPLGVTGGIGTCCCTTGGGAGTCACTGGGGGAATTG
POLB-ASH2Lchr842227506chr837976787717RPLGVTGGIAGTCCCTTGGGAGTCACTGGGGGAATTGCAG
POLB-ASH2Lchr842227506chr837976787718RPLGVTGGIAAGTCCCTTGGGAGTCACTGGGGGAATTGCAGCAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
POLB-ASH2Lchr842227506chr837976787217NEYTIRPLGVTGGIAATGAGTACACCATCCGTCCCTTGGGAGTCACTGGGGGAATTGCAG
POLB-ASH2Lchr842227506chr837976787318EYTIRPLGVTGGIAAAGTACACCATCCGTCCCTTGGGAGTCACTGGGGGAATTGCAGCAG

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Information of the samples that have these potential fusion neoantigens of POLB-ASH2L

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
OVPOLB-ASH2Lchr842227506ENST00000265421chr837976787ENST00000250635TCGA-WR-A838

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Potential target of CAR-T therapy development for POLB-ASH2L

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 POLB-ASH2L

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 POLB-ASH2L

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