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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:LETMD1-HTRA4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LETMD1-HTRA4
FusionPDB ID: 44493
FusionGDB2.0 ID: 44493
HgeneTgene
Gene symbol

LETMD1

HTRA4

Gene ID

25875

203100

Gene nameLETM1 domain containing 1HtrA serine peptidase 4
Synonyms1110019O13Rik|HCCR|HCCR-1|HCCR-2|HCCR1|HCCR2|HCRR-2|SLC55A3-
Cytomap

12q13.12

8p11.22

Type of geneprotein-codingprotein-coding
DescriptionLETM1 domain-containing protein 1cervical cancer 1 proto-oncogene protein p40cervical cancer proto-oncogene 2 proteinepididymis secretory sperm binding proteinhuman cervical cancer oncogeneregulator of TP53serine protease HTRA4high-temperature requirement factor A4probable serine protease HTRA4
Modification date2020032220200315
UniProtAcc

Q6P1Q0

Main function of 5'-partner protein: FUNCTION: Involved in tumorigenesis and may function as a negative regulator of the p53/TP53. {ECO:0000269|PubMed:12879013}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000262055, ENST00000380123, 
ENST00000418425, ENST00000547008, 
ENST00000552739, ENST00000548516, 
ENST00000550929, 
ENST00000302495, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 3=275 X 7 X 5=175
# samples 37
** MAII scorelog2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(7/175*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LETMD1 [Title/Abstract] AND HTRA4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LETMD1 [Title/Abstract] AND HTRA4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LETMD1(51442261)-HTRA4(38840471), # samples:1
Anticipated loss of major functional domain due to fusion event.LETMD1-HTRA4 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.
LETMD1-HTRA4 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
TgeneHTRA4

GO:0006508

proteolysis

18387192



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/chr12:51442261/chr8:38840471)
- 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 LETMD1 (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 HTRA4 (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)
ENST00000262055LETMD1chr1251442261+ENST00000302495HTRA4chr838840471+98416139419126
ENST00000380123LETMD1chr1251442261+ENST00000302495HTRA4chr838840471+97515230410126
ENST00000418425LETMD1chr1251442261+ENST00000302495HTRA4chr838840471+96414119399126
ENST00000547008LETMD1chr1251442261+ENST00000302495HTRA4chr838840471+96113816396126
ENST00000552739LETMD1chr1251442261+ENST00000302495HTRA4chr838840471+95613311391126

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
ENST00000262055ENST00000302495LETMD1chr1251442261+HTRA4chr838840471+0.0264222450.9735778
ENST00000380123ENST00000302495LETMD1chr1251442261+HTRA4chr838840471+0.022423080.9775769
ENST00000418425ENST00000302495LETMD1chr1251442261+HTRA4chr838840471+0.0281175150.97188246
ENST00000547008ENST00000302495LETMD1chr1251442261+HTRA4chr838840471+0.0292089670.970791
ENST00000552739ENST00000302495LETMD1chr1251442261+HTRA4chr838840471+0.0238723230.9761277

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 LETMD1-HTRA4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LETMD1chr1251442261HTRA4chr83884047113341QLGRSGLAWGAPRLSEELKMHYPDFP
LETMD1chr1251442261HTRA4chr83884047113841QLGRSGLAWGAPRLSEELKMHYPDFP
LETMD1chr1251442261HTRA4chr83884047114141QLGRSGLAWGAPRLSEELKMHYPDFP
LETMD1chr1251442261HTRA4chr83884047115241QLGRSGLAWGAPRLSEELKMHYPDFP
LETMD1chr1251442261HTRA4chr83884047116141QLGRSGLAWGAPRLSEELKMHYPDFP

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Potential FusionNeoAntigen Information of LETMD1-HTRA4 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.
LETMD1-HTRA4_51442261_38840471.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)
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:02APRLSEEL0.99980.69481018
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:05APRLSEEL0.99970.58191018
LETMD1-HTRA4chr1251442261chr838840471161HLA-B82:01APRLSEEL0.59860.73931018
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:22GLAWGAPRL0.9910.8138514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:13GLAWGAPRL0.98360.8928514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:27GLAWGAPRL0.98050.8514514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:11GLAWGAPRL0.96960.8498514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:24GLAWGAPRL0.96920.8486514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:30GLAWGAPRL0.96920.8486514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:67GLAWGAPRL0.96920.8486514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:60GLAWGAPRL0.96850.8438514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:38GLAWGAPRL0.96550.8966514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:16GLAWGAPRL0.96360.8205514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:04GLAWGAPRL0.94860.9152514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:17GLAWGAPRL0.93540.8844514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:35GLAWGAPRL0.87370.8468514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:19GLAWGAPRL0.86130.7699514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:29GLAWGAPRL0.83050.8415514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:20GLAWGAPRL0.82410.8533514
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:01RLSEELKMHY0.99990.93141222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:25RLSEELKMHY0.99520.94041222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:02APRLSEELKM0.99250.66321020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:05APRLSEELKM0.99180.53681020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B27:04APRLSEELKM0.9660.72231020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B27:05APRLSEELKM0.95450.70091020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B27:05GAPRLSEELKM0.99950.6526920
LETMD1-HTRA4chr1251442261chr838840471161HLA-B27:07GAPRLSEELKM0.9980.6764920
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:12APRLSEEL0.99840.77391018
LETMD1-HTRA4chr1251442261chr838840471161HLA-B42:02APRLSEEL0.99090.51431018
LETMD1-HTRA4chr1251442261chr838840471161HLA-B42:01APRLSEEL0.98890.51331018
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:04APRLSEEL0.97660.63281018
LETMD1-HTRA4chr1251442261chr838840471161HLA-B39:10APRLSEEL0.52810.93611018
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:02GLAWGAPRL0.99120.7436514
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:01GLAWGAPRL0.96920.8486514
LETMD1-HTRA4chr1251442261chr838840471161HLA-C01:17GAPRLSEEL0.86970.9814918
LETMD1-HTRA4chr1251442261chr838840471161HLA-C01:30GAPRLSEEL0.72580.9797918
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:07RLSEELKMHY0.99940.79271222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:12APRLSEELKM0.99050.74491020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:04RLSEELKMHY0.98080.94221222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:05RLSEELKMHY0.92770.92481222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:04APRLSEELKM0.91030.57371020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B42:01APRLSEELKM0.66770.54531020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B27:03APRLSEELKM0.54970.74951020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:22APRLSEEL0.99980.69481018
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:09APRLSEEL0.99970.69671018
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:26APRLSEEL0.89810.5641018
LETMD1-HTRA4chr1251442261chr838840471161HLA-B82:02APRLSEEL0.59860.73931018
LETMD1-HTRA4chr1251442261chr838840471161HLA-B67:01APRLSEEL0.55290.78131018
LETMD1-HTRA4chr1251442261chr838840471161HLA-A02:03GLAWGAPRL0.99060.8911514
LETMD1-HTRA4chr1251442261chr838840471161HLA-C01:02GAPRLSEEL0.85980.9805918
LETMD1-HTRA4chr1251442261chr838840471161HLA-C01:03GAPRLSEEL0.8390.9803918
LETMD1-HTRA4chr1251442261chr838840471161HLA-B40:21GLAWGAPRL0.01860.9487514
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:34RLSEELKMHY0.99990.93141222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:50RLSEELKMHY0.99990.90881222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:27RLSEELKMHY0.99990.94511222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:33RLSEELKMHY0.99990.93141222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:125RLSEELKMHY0.99990.93141222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:12RLSEELKMHY0.99980.90991222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:135RLSEELKMHY0.99980.93491222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:24RLSEELKMHY0.99960.94391222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:35RLSEELKMHY0.99930.92791222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:39RLSEELKMHY0.99490.85541222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:09APRLSEELKM0.99310.66541020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B07:22APRLSEELKM0.99250.66321020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B27:06APRLSEELKM0.95670.71671020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B27:08APRLSEELKM0.95580.65341020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B15:20RLSEELKMHY0.93420.94611222
LETMD1-HTRA4chr1251442261chr838840471161HLA-B27:09APRLSEELKM0.85130.67271020
LETMD1-HTRA4chr1251442261chr838840471161HLA-B27:08GAPRLSEELKM0.99930.59920
LETMD1-HTRA4chr1251442261chr838840471161HLA-B27:09GAPRLSEELKM0.99870.5929920

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Potential FusionNeoAntigen Information of LETMD1-HTRA4 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 LETMD1-HTRA4

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
4801LAWGAPRLSEELKMLETMD1HTRA4chr1251442261chr838840471161

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LETMD1-HTRA4

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-B14:023BVN4801LAWGAPRLSEELKM-7.9962-8.1096
HLA-B14:023BVN4801LAWGAPRLSEELKM-5.70842-6.74372
HLA-B52:013W394801LAWGAPRLSEELKM-6.83737-6.95077
HLA-B52:013W394801LAWGAPRLSEELKM-4.4836-5.5189
HLA-A11:014UQ24801LAWGAPRLSEELKM-10.0067-10.1201
HLA-A11:014UQ24801LAWGAPRLSEELKM-9.03915-10.0745
HLA-A24:025HGA4801LAWGAPRLSEELKM-6.56204-6.67544
HLA-A24:025HGA4801LAWGAPRLSEELKM-5.42271-6.45801
HLA-B44:053DX84801LAWGAPRLSEELKM-7.85648-8.89178
HLA-B44:053DX84801LAWGAPRLSEELKM-5.3978-5.5112
HLA-A02:016TDR4801LAWGAPRLSEELKM-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LETMD1-HTRA4

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
LETMD1-HTRA4chr1251442261chr8388404711018APRLSEELGGCCCCTCGCCTTAGTGAAGAATT
LETMD1-HTRA4chr1251442261chr8388404711020APRLSEELKMGGCCCCTCGCCTTAGTGAAGAATTGAAAAT
LETMD1-HTRA4chr1251442261chr8388404711222RLSEELKMHYTCGCCTTAGTGAAGAATTGAAAATGCATTA
LETMD1-HTRA4chr1251442261chr838840471514GLAWGAPRLTGGCCTGGCTTGGGGGGCCCCTCGCCT
LETMD1-HTRA4chr1251442261chr838840471918GAPRLSEELGGGGGCCCCTCGCCTTAGTGAAGAATT
LETMD1-HTRA4chr1251442261chr838840471920GAPRLSEELKMGGGGGCCCCTCGCCTTAGTGAAGAATTGAAAAT

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 LETMD1-HTRA4

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
PAADLETMD1-HTRA4chr1251442261ENST00000262055chr838840471ENST00000302495TCGA-F2-7273

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Potential target of CAR-T therapy development for LETMD1-HTRA4

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 LETMD1-HTRA4

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 LETMD1-HTRA4

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