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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:LRIG1-BDH1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LRIG1-BDH1
FusionPDB ID: 49672
FusionGDB2.0 ID: 49672
HgeneTgene
Gene symbol

LRIG1

BDH1

Gene ID

26018

622

Gene nameleucine rich repeats and immunoglobulin like domains 13-hydroxybutyrate dehydrogenase 1
SynonymsLIG-1|LIG1BDH|SDR9C1
Cytomap

3p14.1

3q29

Type of geneprotein-codingprotein-coding
Descriptionleucine-rich repeats and immunoglobulin-like domains protein 1leucine-rich repeat protein LRIG1ortholog of mouse integral membrane glycoprotein LIG-1D-beta-hydroxybutyrate dehydrogenase, mitochondrial(R)-3-hydroxybutyrate dehydrogenase3-hydroxybutyrate dehydrogenase (heart, mitochondrial)3-hydroxybutyrate dehydrogenase, type 1epididymis secretory sperm binding proteinshort chain dehydrogenase/red
Modification date2020032020200313
UniProtAcc

Q96JA1

Main function of 5'-partner protein: FUNCTION: Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation. {ECO:0000269|PubMed:15282549}.

Q02338

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000273261, ENST00000383703, 
ENST00000496559, 
ENST00000441275, 
ENST00000476764, ENST00000358186, 
ENST00000392378, ENST00000392379, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 13 X 6=8588 X 8 X 8=512
# samples 1414
** MAII scorelog2(14/858*10)=-2.61555082055458
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/512*10)=-1.87071698305503
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LRIG1 [Title/Abstract] AND BDH1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LRIG1 [Title/Abstract] AND BDH1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LRIG1(66501983)-BDH1(197260432), # samples:1
Anticipated loss of major functional domain due to fusion event.LRIG1-BDH1 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.
LRIG1-BDH1 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.
LRIG1-BDH1 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.
LRIG1-BDH1 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


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/chr3:66501983/chr3:197260432)
- 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 LRIG1 (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 BDH1 (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)
ENST00000273261LRIG1chr366501983-ENST00000392379BDH1chr3197260432-39518901441838564
ENST00000273261LRIG1chr366501983-ENST00000392378BDH1chr3197260432-39518901441838564
ENST00000273261LRIG1chr366501983-ENST00000358186BDH1chr3197260432-39518901441838564
ENST00000383703LRIG1chr366501983-ENST00000392379BDH1chr3197260432-4030969101917635
ENST00000383703LRIG1chr366501983-ENST00000392378BDH1chr3197260432-4030969101917635
ENST00000383703LRIG1chr366501983-ENST00000358186BDH1chr3197260432-4030969101917635

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
ENST00000273261ENST00000392379LRIG1chr366501983-BDH1chr3197260432-0.0030643220.9969357
ENST00000273261ENST00000392378LRIG1chr366501983-BDH1chr3197260432-0.0030643220.9969357
ENST00000273261ENST00000358186LRIG1chr366501983-BDH1chr3197260432-0.0030643220.9969357
ENST00000383703ENST00000392379LRIG1chr366501983-BDH1chr3197260432-0.003063890.9969361
ENST00000383703ENST00000392378LRIG1chr366501983-BDH1chr3197260432-0.003063890.9969361
ENST00000383703ENST00000358186LRIG1chr366501983-BDH1chr3197260432-0.003063890.9969361

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 LRIG1-BDH1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LRIG1chr366501983BDH1chr3197260432890249LGAASSHVVSLFLRPLLLGSTSFIPI
LRIG1chr366501983BDH1chr3197260432969320LGAASSHVVSLFLRPLLLGSTSFIPI

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Potential FusionNeoAntigen Information of LRIG1-BDH1 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.
LRIG1-BDH1_66501983_197260432.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)
LRIG1-BDH1chr366501983chr3197260432890HLA-B08:01SLFLRPLL0.99890.7309917
LRIG1-BDH1chr366501983chr3197260432890HLA-B08:09SLFLRPLL0.99790.9153917
LRIG1-BDH1chr366501983chr3197260432890HLA-B08:01SLFLRPLLL0.98550.8234918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:22SLFLRPLLL0.97750.7584918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:13SLFLRPLLL0.95840.8853918
LRIG1-BDH1chr366501983chr3197260432890HLA-B08:09SLFLRPLLL0.95820.9408918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:27SLFLRPLLL0.95450.8462918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:11SLFLRPLLL0.9520.741918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:24SLFLRPLLL0.95080.704918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:30SLFLRPLLL0.95080.704918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:67SLFLRPLLL0.95080.704918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:60SLFLRPLLL0.94910.6884918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:04SLFLRPLLL0.93710.8621918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:17SLFLRPLLL0.93430.8382918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:16SLFLRPLLL0.93050.7012918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:38SLFLRPLLL0.92660.8709918
LRIG1-BDH1chr366501983chr3197260432890HLA-A32:13SLFLRPLLL0.9110.9933918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:35SLFLRPLLL0.87260.7334918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:29SLFLRPLLL0.85830.7097918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:20SLFLRPLLL0.84010.7108918
LRIG1-BDH1chr366501983chr3197260432890HLA-A30:08SLFLRPLLL0.82120.8834918
LRIG1-BDH1chr366501983chr3197260432890HLA-B14:02SLFLRPLLL0.7780.9668918
LRIG1-BDH1chr366501983chr3197260432890HLA-B14:01SLFLRPLLL0.7780.9668918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:19SLFLRPLLL0.74450.7962918
LRIG1-BDH1chr366501983chr3197260432890HLA-B48:01SLFLRPLLL0.26730.5979918
LRIG1-BDH1chr366501983chr3197260432890HLA-B13:02SLFLRPLLL0.13580.9375918
LRIG1-BDH1chr366501983chr3197260432890HLA-B13:01SLFLRPLLL0.11070.9932918
LRIG1-BDH1chr366501983chr3197260432890HLA-B52:01SLFLRPLLL0.06290.9922918
LRIG1-BDH1chr366501983chr3197260432890HLA-B42:02SLFLRPLLL0.99120.8081918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:02SLFLRPLLL0.97920.7058918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:05SLFLRPLLL0.97550.8122918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:07SLFLRPLLL0.9530.7497918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:01SLFLRPLLL0.95080.704918
LRIG1-BDH1chr366501983chr3197260432890HLA-C15:06SLFLRPLLL0.79030.9535918
LRIG1-BDH1chr366501983chr3197260432890HLA-C04:14SLFLRPLLL0.71790.9855918
LRIG1-BDH1chr366501983chr3197260432890HLA-C04:06SLFLRPLLL0.68250.9888918
LRIG1-BDH1chr366501983chr3197260432890HLA-C07:05SLFLRPLLL0.59150.9873918
LRIG1-BDH1chr366501983chr3197260432890HLA-C07:10SLFLRPLLL0.54240.9871918
LRIG1-BDH1chr366501983chr3197260432890HLA-C07:19SLFLRPLLL0.53880.9379918
LRIG1-BDH1chr366501983chr3197260432890HLA-C07:29SLFLRPLLL0.52610.9841918
LRIG1-BDH1chr366501983chr3197260432890HLA-C12:16SLFLRPLLL0.52310.9916918
LRIG1-BDH1chr366501983chr3197260432890HLA-C07:13SLFLRPLLL0.4980.9872918
LRIG1-BDH1chr366501983chr3197260432890HLA-B14:03SLFLRPLLL0.44720.9437918
LRIG1-BDH1chr366501983chr3197260432890HLA-C02:06SLFLRPLLL0.43270.9955918
LRIG1-BDH1chr366501983chr3197260432890HLA-B15:04SLFLRPLLL0.42190.9837918
LRIG1-BDH1chr366501983chr3197260432890HLA-C07:27SLFLRPLLL0.41330.9888918
LRIG1-BDH1chr366501983chr3197260432890HLA-C07:95SLFLRPLLL0.33840.9085918
LRIG1-BDH1chr366501983chr3197260432890HLA-C01:17SLFLRPLLL0.15380.9825918
LRIG1-BDH1chr366501983chr3197260432890HLA-C01:30SLFLRPLLL0.13410.986918
LRIG1-BDH1chr366501983chr3197260432890HLA-B08:18SLFLRPLL0.99890.7309917
LRIG1-BDH1chr366501983chr3197260432890HLA-B08:12SLFLRPLL0.96230.9275917
LRIG1-BDH1chr366501983chr3197260432890HLA-B08:18SLFLRPLLL0.98550.8234918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:03SLFLRPLLL0.97860.8316918
LRIG1-BDH1chr366501983chr3197260432890HLA-A32:01SLFLRPLLL0.95210.9939918
LRIG1-BDH1chr366501983chr3197260432890HLA-A02:14SLFLRPLLL0.94670.8918
LRIG1-BDH1chr366501983chr3197260432890HLA-C06:02SLFLRPLLL0.85780.9987918
LRIG1-BDH1chr366501983chr3197260432890HLA-C06:17SLFLRPLLL0.85780.9987918
LRIG1-BDH1chr366501983chr3197260432890HLA-C06:06SLFLRPLLL0.78220.9968918
LRIG1-BDH1chr366501983chr3197260432890HLA-C03:67SLFLRPLLL0.76670.9949918
LRIG1-BDH1chr366501983chr3197260432890HLA-C15:05SLFLRPLLL0.76550.9541918
LRIG1-BDH1chr366501983chr3197260432890HLA-C15:02SLFLRPLLL0.74820.9344918
LRIG1-BDH1chr366501983chr3197260432890HLA-B08:12SLFLRPLLL0.72760.9313918
LRIG1-BDH1chr366501983chr3197260432890HLA-C07:04SLFLRPLLL0.71660.9917918
LRIG1-BDH1chr366501983chr3197260432890HLA-C04:04SLFLRPLLL0.64550.9853918
LRIG1-BDH1chr366501983chr3197260432890HLA-C06:08SLFLRPLLL0.54860.9977918
LRIG1-BDH1chr366501983chr3197260432890HLA-C07:17SLFLRPLLL0.52770.9912918
LRIG1-BDH1chr366501983chr3197260432890HLA-B15:73SLFLRPLLL0.440.9835918
LRIG1-BDH1chr366501983chr3197260432890HLA-C17:01SLFLRPLLL0.43040.9787918
LRIG1-BDH1chr366501983chr3197260432890HLA-C07:01SLFLRPLLL0.38550.904918
LRIG1-BDH1chr366501983chr3197260432890HLA-B15:30SLFLRPLLL0.35290.9825918
LRIG1-BDH1chr366501983chr3197260432890HLA-C18:01SLFLRPLLL0.3210.9853918
LRIG1-BDH1chr366501983chr3197260432890HLA-C01:02SLFLRPLLL0.17070.9824918
LRIG1-BDH1chr366501983chr3197260432890HLA-C01:03SLFLRPLLL0.13350.9707918
LRIG1-BDH1chr366501983chr3197260432890HLA-B40:21SLFLRPLLL0.06130.5401918

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Potential FusionNeoAntigen Information of LRIG1-BDH1 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 LRIG1-BDH1

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
3546HVVSLFLRPLLLGSLRIG1BDH1chr366501983chr3197260432890

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LRIG1-BDH1

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-B14:023BVN3546HVVSLFLRPLLLGS-7.15543-7.26883
HLA-B14:023BVN3546HVVSLFLRPLLLGS-4.77435-5.80965
HLA-B52:013W393546HVVSLFLRPLLLGS-6.80875-6.92215
HLA-B52:013W393546HVVSLFLRPLLLGS-4.20386-5.23916
HLA-A11:014UQ23546HVVSLFLRPLLLGS-7.5194-8.5547
HLA-A11:014UQ23546HVVSLFLRPLLLGS-6.9601-7.0735
HLA-A24:025HGA3546HVVSLFLRPLLLGS-7.52403-7.63743
HLA-A24:025HGA3546HVVSLFLRPLLLGS-5.82433-6.85963
HLA-B27:056PYJ3546HVVSLFLRPLLLGS-3.28285-4.31815
HLA-B44:053DX83546HVVSLFLRPLLLGS-5.91172-6.94702
HLA-B44:053DX83546HVVSLFLRPLLLGS-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of LRIG1-BDH1

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
LRIG1-BDH1chr366501983chr3197260432917SLFLRPLLCTCTCTCTTTCTACGCCCACTATT
LRIG1-BDH1chr366501983chr3197260432918SLFLRPLLLCTCTCTCTTTCTACGCCCACTATTGCT

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 LRIG1-BDH1

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
UCECLRIG1-BDH1chr366501983ENST00000273261chr3197260432ENST00000358186TCGA-FI-A2CY-01A

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Potential target of CAR-T therapy development for LRIG1-BDH1

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 LRIG1-BDH1

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 LRIG1-BDH1

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