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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:GLRB-KLHL2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GLRB-KLHL2
FusionPDB ID: 33341
FusionGDB2.0 ID: 33341
HgeneTgene
Gene symbol

GLRB

KLHL2

Gene ID

2743

11275

Gene nameglycine receptor betakelch like family member 2
SynonymsHKPX2ABP-KELCH|MAV|MAYVEN
Cytomap

4q32.1

4q32.3

Type of geneprotein-codingprotein-coding
Descriptionglycine receptor subunit betaglycine receptor 58 kDa subunitglycine receptor, beta subunitkelch-like protein 2actin-binding protein Mayvenkelch-like 2, Mayven
Modification date2020031320200327
UniProtAcc

P48167

Main function of 5'-partner protein: FUNCTION: Glycine receptors are ligand-gated chloride channels. GLRB does not form ligand-gated ion channels by itself, but is part of heteromeric ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:8717357, PubMed:15302677, PubMed:16144831, PubMed:22715885, PubMed:25445488, PubMed:11929858, PubMed:23238346). Heteropentameric channels composed of GLRB and GLRA1 are activated by lower glycine levels than homopentameric GLRA1 (PubMed:8717357). Plays an important role in the down-regulation of neuronal excitability (PubMed:11929858, PubMed:23238346). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). {ECO:0000269|PubMed:11929858, ECO:0000269|PubMed:15302677, ECO:0000269|PubMed:16144831, ECO:0000269|PubMed:22715885, ECO:0000269|PubMed:23238346, ECO:0000269|PubMed:25445488, ECO:0000269|PubMed:8717357}.

Q96CT2

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000264428, ENST00000509282, 
ENST00000512619, ENST00000541722, 
ENST00000421009, ENST00000506761, 
ENST00000509028, ENST00000538127, 
ENST00000226725, ENST00000514860, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 3=483 X 3 X 3=27
# samples 43
** MAII scorelog2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: GLRB [Title/Abstract] AND KLHL2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GLRB [Title/Abstract] AND KLHL2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GLRB(157999298)-KLHL2(166149959), # samples:1
Anticipated loss of major functional domain due to fusion event.GLRB-KLHL2 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.
GLRB-KLHL2 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.
GLRB-KLHL2 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.
GLRB-KLHL2 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
HgeneGLRB

GO:0006811

ion transport

8717357

HgeneGLRB

GO:0007218

neuropeptide signaling pathway

8717357



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/chr4:157999298/chr4:166149959)
- 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 GLRB (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 KLHL2 (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)
ENST00000264428GLRBchr4157999298+ENST00000226725KLHL2chr4166149959+31153921292021630
ENST00000264428GLRBchr4157999298+ENST00000514860KLHL2chr4166149959+24203921292021630
ENST00000541722GLRBchr4157999298+ENST00000226725KLHL2chr4166149959+3047324611953630
ENST00000541722GLRBchr4157999298+ENST00000514860KLHL2chr4166149959+2352324611953630
ENST00000512619GLRBchr4157999298+ENST00000226725KLHL2chr4166149959+2977254811883600
ENST00000512619GLRBchr4157999298+ENST00000514860KLHL2chr4166149959+2282254811883600
ENST00000509282GLRBchr4157999298+ENST00000226725KLHL2chr4166149959+3030307231936637
ENST00000509282GLRBchr4157999298+ENST00000514860KLHL2chr4166149959+2335307231936637

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
ENST00000264428ENST00000226725GLRBchr4157999298+KLHL2chr4166149959+0.000303720.99969625
ENST00000264428ENST00000514860GLRBchr4157999298+KLHL2chr4166149959+0.0015384850.9984615
ENST00000541722ENST00000226725GLRBchr4157999298+KLHL2chr4166149959+0.0003244260.99967563
ENST00000541722ENST00000514860GLRBchr4157999298+KLHL2chr4166149959+0.0016601490.9983398
ENST00000512619ENST00000226725GLRBchr4157999298+KLHL2chr4166149959+0.0002748480.99972516
ENST00000512619ENST00000514860GLRBchr4157999298+KLHL2chr4166149959+0.0012775570.9987224
ENST00000509282ENST00000226725GLRBchr4157999298+KLHL2chr4166149959+0.0002627160.9997373
ENST00000509282ENST00000514860GLRBchr4157999298+KLHL2chr4166149959+0.0013566450.99864334

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 GLRB-KLHL2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GLRBchr4157999298KLHL2chr416614995925457KKGKGKKKQYLCPSQNLLCDVTIVAE
GLRBchr4157999298KLHL2chr416614995930794KKGKGKKKQYLCPSQNLLCDVTIVAE
GLRBchr4157999298KLHL2chr416614995932487KKGKGKKKQYLCPSQNLLCDVTIVAE
GLRBchr4157999298KLHL2chr416614995939287KKGKGKKKQYLCPSQNLLCDVTIVAE

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Potential FusionNeoAntigen Information of GLRB-KLHL2 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.
GLRB-KLHL2_157999298_166149959.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)
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:22YLCPSQNLL0.99570.5383918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:67YLCPSQNLL0.9940.6286918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:30YLCPSQNLL0.9940.6286918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:24YLCPSQNLL0.9940.6286918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:60YLCPSQNLL0.99380.5896918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:11YLCPSQNLL0.99370.6332918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:21YLCPSQNLL0.99160.714918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:27YLCPSQNLL0.99110.5844918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A24:25QYLCPSQNL0.99110.541817
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:13YLCPSQNLL0.98970.6933918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A24:20QYLCPSQNL0.98910.5371817
GLRB-KLHL2chr4157999298chr4166149959392HLA-A24:15QYLCPSQNL0.98860.5507817
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:04YLCPSQNLL0.98610.5614918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A24:31QYLCPSQNL0.98490.5253817
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:17YLCPSQNLL0.98330.5076918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:38YLCPSQNLL0.97060.6244918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:19YLCPSQNLL0.97020.5836918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:35YLCPSQNLL0.96550.651918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:29YLCPSQNLL0.90360.6334918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:20YLCPSQNLL0.88930.6318918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A24:14QYLCPSQNL0.87350.6663817
GLRB-KLHL2chr4157999298chr4166149959392HLA-B13:01YLCPSQNLL0.12690.878918
GLRB-KLHL2chr4157999298chr4166149959392HLA-B48:01KQYLCPSQNL0.9870.671717
GLRB-KLHL2chr4157999298chr4166149959392HLA-A24:15QYLCPSQNLL0.98380.5099818
GLRB-KLHL2chr4157999298chr4166149959392HLA-A24:31QYLCPSQNLL0.97310.5007818
GLRB-KLHL2chr4157999298chr4166149959392HLA-A24:14QYLCPSQNLL0.88150.6424818
GLRB-KLHL2chr4157999298chr4166149959392HLA-B13:02KQYLCPSQNL0.75090.8131717
GLRB-KLHL2chr4157999298chr4166149959392HLA-B13:01KQYLCPSQNL0.6740.9785717
GLRB-KLHL2chr4157999298chr4166149959392HLA-B48:01KQYLCPSQNLL0.97810.559718
GLRB-KLHL2chr4157999298chr4166149959392HLA-B13:02KQYLCPSQNLL0.93820.7918718
GLRB-KLHL2chr4157999298chr4166149959392HLA-B13:01KQYLCPSQNLL0.88050.9735718
GLRB-KLHL2chr4157999298chr4166149959392HLA-B52:01KQYLCPSQNLL0.46710.9766718
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:07YLCPSQNLL0.99450.6194918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:01YLCPSQNLL0.9940.6286918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A24:02QYLCPSQNL0.98910.5371817
GLRB-KLHL2chr4157999298chr4166149959392HLA-C04:06YLCPSQNLL0.96220.9066918
GLRB-KLHL2chr4157999298chr4166149959392HLA-B15:04KQYLCPSQNL0.97490.9184717
GLRB-KLHL2chr4157999298chr4166149959392HLA-B48:03KQYLCPSQNL0.85260.7164717
GLRB-KLHL2chr4157999298chr4166149959392HLA-B15:04KQYLCPSQNLL0.99280.912718
GLRB-KLHL2chr4157999298chr4166149959392HLA-B48:03KQYLCPSQNLL0.80610.5705718
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:03YLCPSQNLL0.99480.659918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:14YLCPSQNLL0.99170.6232918
GLRB-KLHL2chr4157999298chr4166149959392HLA-A02:06YLCPSQNLL0.99160.714918
GLRB-KLHL2chr4157999298chr4166149959392HLA-C01:03YLCPSQNLL0.9780.9165918
GLRB-KLHL2chr4157999298chr4166149959392HLA-C04:04YLCPSQNLL0.93970.8705918
GLRB-KLHL2chr4157999298chr4166149959392HLA-B15:73YLCPSQNLL0.79850.8663918
GLRB-KLHL2chr4157999298chr4166149959392HLA-B15:30YLCPSQNLL0.66870.8626918
GLRB-KLHL2chr4157999298chr4166149959392HLA-C07:04YLCPSQNLL0.66630.9178918
GLRB-KLHL2chr4157999298chr4166149959392HLA-C17:01YLCPSQNLL0.60990.8602918
GLRB-KLHL2chr4157999298chr4166149959392HLA-C14:02QYLCPSQNL0.21190.9783817
GLRB-KLHL2chr4157999298chr4166149959392HLA-C14:03QYLCPSQNL0.21190.9783817
GLRB-KLHL2chr4157999298chr4166149959392HLA-B15:68KQYLCPSQNL0.99430.7292717
GLRB-KLHL2chr4157999298chr4166149959392HLA-B15:73KQYLCPSQNL0.98680.9651717
GLRB-KLHL2chr4157999298chr4166149959392HLA-B15:30KQYLCPSQNL0.97690.9382717
GLRB-KLHL2chr4157999298chr4166149959392HLA-B40:12KQYLCPSQNL0.85260.7164717
GLRB-KLHL2chr4157999298chr4166149959392HLA-B40:21KQYLCPSQNL0.68770.72717
GLRB-KLHL2chr4157999298chr4166149959392HLA-B15:68KQYLCPSQNLL0.99330.6588718
GLRB-KLHL2chr4157999298chr4166149959392HLA-B15:73KQYLCPSQNLL0.98760.9607718
GLRB-KLHL2chr4157999298chr4166149959392HLA-B15:30KQYLCPSQNLL0.96140.9473718
GLRB-KLHL2chr4157999298chr4166149959392HLA-B40:21KQYLCPSQNLL0.880.5931718
GLRB-KLHL2chr4157999298chr4166149959392HLA-B40:49KQYLCPSQNLL0.86240.5108718
GLRB-KLHL2chr4157999298chr4166149959392HLA-B40:12KQYLCPSQNLL0.80610.5705718

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Potential FusionNeoAntigen Information of GLRB-KLHL2 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 GLRB-KLHL2

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
4355KKQYLCPSQNLLCDGLRBKLHL2chr4157999298chr4166149959392

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GLRB-KLHL2

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-B14:023BVN4355KKQYLCPSQNLLCD-7.15543-7.26883
HLA-B14:023BVN4355KKQYLCPSQNLLCD-4.77435-5.80965
HLA-B52:013W394355KKQYLCPSQNLLCD-6.80875-6.92215
HLA-B52:013W394355KKQYLCPSQNLLCD-4.20386-5.23916
HLA-A11:014UQ24355KKQYLCPSQNLLCD-7.5194-8.5547
HLA-A11:014UQ24355KKQYLCPSQNLLCD-6.9601-7.0735
HLA-A24:025HGA4355KKQYLCPSQNLLCD-7.52403-7.63743
HLA-A24:025HGA4355KKQYLCPSQNLLCD-5.82433-6.85963
HLA-B27:056PYJ4355KKQYLCPSQNLLCD-3.28285-4.31815
HLA-B44:053DX84355KKQYLCPSQNLLCD-5.91172-6.94702
HLA-B44:053DX84355KKQYLCPSQNLLCD-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of GLRB-KLHL2

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
GLRB-KLHL2chr4157999298chr4166149959717KQYLCPSQNLGCAGTATCTATGCCCATCTCAAAATTTGCT
GLRB-KLHL2chr4157999298chr4166149959718KQYLCPSQNLLGCAGTATCTATGCCCATCTCAAAATTTGCTGTG
GLRB-KLHL2chr4157999298chr4166149959817QYLCPSQNLGTATCTATGCCCATCTCAAAATTTGCT
GLRB-KLHL2chr4157999298chr4166149959818QYLCPSQNLLGTATCTATGCCCATCTCAAAATTTGCTGTG
GLRB-KLHL2chr4157999298chr4166149959918YLCPSQNLLTCTATGCCCATCTCAAAATTTGCTGTG

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 GLRB-KLHL2

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
BRCAGLRB-KLHL2chr4157999298ENST00000264428chr4166149959ENST00000226725TCGA-E9-A228-01A

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Potential target of CAR-T therapy development for GLRB-KLHL2

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 GLRB-KLHL2

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 GLRB-KLHL2

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