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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:PTPN6-LEPREL2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PTPN6-LEPREL2
FusionPDB ID: 70290
FusionGDB2.0 ID: 70292
HgeneTgene
Gene symbol

PTPN6

LEPREL2

Gene ID

5777

10536

Gene nameprotein tyrosine phosphatase non-receptor type 6prolyl 3-hydroxylase 3
SynonymsHCP|HCPH|HPTP1C|PTP-1C|SH-PTP1|SHP-1|SHP-1L|SHP1GRCB|HSU47926|LEPREL2
Cytomap

12p13.31

12p13.31

Type of geneprotein-codingprotein-coding
Descriptiontyrosine-protein phosphatase non-receptor type 6hematopoietic cell phosphatasehematopoietic cell protein-tyrosine phosphataseprotein-tyrosine phosphatase 1Cprotein-tyrosine phosphatase SHP-1prolyl 3-hydroxylase 3gene rich cluster, Bleprecan-like 2procollagen-proline 3-dioxygenaseprotein B
Modification date2020032020200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000318974, ENST00000399448, 
ENST00000447931, ENST00000456013, 
ENST00000539029, 
ENST00000538102, 
ENST00000251761, ENST00000396725, 
ENST00000606935, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 5 X 4=1002 X 2 X 2=8
# samples 62
** MAII scorelog2(6/100*10)=-0.736965594166206
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: PTPN6 [Title/Abstract] AND LEPREL2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PTPN6 [Title/Abstract] AND LEPREL2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PTPN6(7066948)-LEPREL2(6948164), # samples:2
Anticipated loss of major functional domain due to fusion event.PTPN6-LEPREL2 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.
PTPN6-LEPREL2 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.
PTPN6-LEPREL2 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.
PTPN6-LEPREL2 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
HgenePTPN6

GO:0006470

protein dephosphorylation

11266449

HgenePTPN6

GO:0018108

peptidyl-tyrosine phosphorylation

9285411|18802077

HgenePTPN6

GO:0030154

cell differentiation

11266449

HgenePTPN6

GO:0070372

regulation of ERK1 and ERK2 cascade

11266449

TgeneLEPREL2

GO:0008285

negative regulation of cell proliferation

19436308



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/chr12:7066948/chr12:6948164)
- 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 PTPN6 (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 LEPREL2 (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)
ENST00000399448PTPN6chr127066948+ENST00000396725LEPREL2chr126948164+20601361411666541
ENST00000399448PTPN6chr127066948+ENST00000251761LEPREL2chr126948164+20601361411666541
ENST00000399448PTPN6chr127066948+ENST00000606935LEPREL2chr126948164+16671361411666542
ENST00000447931PTPN6chr127066948+ENST00000396725LEPREL2chr126948164+1904120581510500
ENST00000447931PTPN6chr127066948+ENST00000251761LEPREL2chr126948164+1904120581510500
ENST00000447931PTPN6chr127066948+ENST00000606935LEPREL2chr126948164+1511120581510501
ENST00000318974PTPN6chr127066948+ENST00000396725LEPREL2chr126948164+214914501691755528
ENST00000318974PTPN6chr127066948+ENST00000251761LEPREL2chr126948164+214914501691755528
ENST00000318974PTPN6chr127066948+ENST00000606935LEPREL2chr126948164+175614501691755529
ENST00000456013PTPN6chr127066948+ENST00000396725LEPREL2chr126948164+214714481671753528
ENST00000456013PTPN6chr127066948+ENST00000251761LEPREL2chr126948164+214714481671753528
ENST00000456013PTPN6chr127066948+ENST00000606935LEPREL2chr126948164+175414481671753529

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
ENST00000399448ENST00000396725PTPN6chr127066948+LEPREL2chr126948164+0.0084987530.9915012
ENST00000399448ENST00000251761PTPN6chr127066948+LEPREL2chr126948164+0.0084987530.9915012
ENST00000399448ENST00000606935PTPN6chr127066948+LEPREL2chr126948164+0.0085671710.9914328
ENST00000447931ENST00000396725PTPN6chr127066948+LEPREL2chr126948164+0.0102300690.98976994
ENST00000447931ENST00000251761PTPN6chr127066948+LEPREL2chr126948164+0.0102300690.98976994
ENST00000447931ENST00000606935PTPN6chr127066948+LEPREL2chr126948164+0.0102216910.98977834
ENST00000318974ENST00000396725PTPN6chr127066948+LEPREL2chr126948164+0.0096018720.99039817
ENST00000318974ENST00000251761PTPN6chr127066948+LEPREL2chr126948164+0.0096018720.99039817
ENST00000318974ENST00000606935PTPN6chr127066948+LEPREL2chr126948164+0.0100986970.9899013
ENST00000456013ENST00000396725PTPN6chr127066948+LEPREL2chr126948164+0.0097044750.9902955
ENST00000456013ENST00000251761PTPN6chr127066948+LEPREL2chr126948164+0.0097044750.9902955
ENST00000456013ENST00000606935PTPN6chr127066948+LEPREL2chr126948164+0.0102454530.9897545

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 PTPN6-LEPREL2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PTPN6chr127066948LEPREL2chr1269481641205399YKLRTLQVSPLDNARVRPRCGRLVAF
PTPN6chr127066948LEPREL2chr1269481641361440YKLRTLQVSPLDNARVRPRCGRLVAF
PTPN6chr127066948LEPREL2chr1269481641448427YKLRTLQVSPLDNARVRPRCGRLVAF
PTPN6chr127066948LEPREL2chr1269481641450427YKLRTLQVSPLDNARVRPRCGRLVAF

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Potential FusionNeoAntigen Information of PTPN6-LEPREL2 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.
PTPN6-LEPREL2_7066948_6948164.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)
PTPN6-LEPREL2chr127066948chr1269481641450HLA-C01:17VSPLDNARV0.54160.979716
PTPN6-LEPREL2chr127066948chr1269481641450HLA-C01:03VSPLDNARV0.57590.9679716
PTPN6-LEPREL2chr127066948chr1269481641450HLA-C01:02VSPLDNARV0.53470.9783716

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Potential FusionNeoAntigen Information of PTPN6-LEPREL2 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.
PTPN6-LEPREL2_7066948_6948164.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)
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1201TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1203TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1205TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1206TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1207TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1210TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1211TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1212TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1213TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1214TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1215TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1217TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1218TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1219TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1220TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1221TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1221RTLQVSPLDNARVRP318
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1223TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1410TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1615TLQVSPLDNARVRPR419
PTPN6-LEPREL2chr127066948chr1269481641450DRB1-1615RTLQVSPLDNARVRP318
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0101LRTLQVSPLDNARVR217
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0101KLRTLQVSPLDNARV116
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0101RTLQVSPLDNARVRP318
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0101YKLRTLQVSPLDNAR015
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0103LRTLQVSPLDNARVR217
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0103KLRTLQVSPLDNARV116
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0103RTLQVSPLDNARVRP318
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0103YKLRTLQVSPLDNAR015
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0104LRTLQVSPLDNARVR217
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0104KLRTLQVSPLDNARV116
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0104RTLQVSPLDNARVRP318
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0104YKLRTLQVSPLDNAR015
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0106LRTLQVSPLDNARVR217
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0106KLRTLQVSPLDNARV116
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0106RTLQVSPLDNARVRP318
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0106YKLRTLQVSPLDNAR015
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0107LRTLQVSPLDNARVR217
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0107KLRTLQVSPLDNARV116
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0107RTLQVSPLDNARVRP318
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0107YKLRTLQVSPLDNAR015
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0108LRTLQVSPLDNARVR217
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0108KLRTLQVSPLDNARV116
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0108RTLQVSPLDNARVRP318
PTPN6-LEPREL2chr127066948chr1269481641450DRB4-0108YKLRTLQVSPLDNAR015

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Fusion breakpoint peptide structures of PTPN6-LEPREL2

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
7636QVSPLDNARVRPRCPTPN6LEPREL2chr127066948chr1269481641450

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PTPN6-LEPREL2

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-B14:023BVN7636QVSPLDNARVRPRC-7.15543-7.26883
HLA-B14:023BVN7636QVSPLDNARVRPRC-4.77435-5.80965
HLA-B52:013W397636QVSPLDNARVRPRC-6.80875-6.92215
HLA-B52:013W397636QVSPLDNARVRPRC-4.20386-5.23916
HLA-A11:014UQ27636QVSPLDNARVRPRC-7.5194-8.5547
HLA-A11:014UQ27636QVSPLDNARVRPRC-6.9601-7.0735
HLA-A24:025HGA7636QVSPLDNARVRPRC-7.52403-7.63743
HLA-A24:025HGA7636QVSPLDNARVRPRC-5.82433-6.85963
HLA-B27:056PYJ7636QVSPLDNARVRPRC-3.28285-4.31815
HLA-B44:053DX87636QVSPLDNARVRPRC-5.91172-6.94702
HLA-B44:053DX87636QVSPLDNARVRPRC-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PTPN6-LEPREL2

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
PTPN6-LEPREL2chr127066948chr126948164716VSPLDNARVGTCTCCCCGCTGGACAATGCTCGGGTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PTPN6-LEPREL2chr127066948chr126948164015YKLRTLQVSPLDNARTACAAACTCCGTACCTTACAGGTCTCCCCGCTGGACAATGCTCGG
PTPN6-LEPREL2chr127066948chr126948164116KLRTLQVSPLDNARVAAACTCCGTACCTTACAGGTCTCCCCGCTGGACAATGCTCGGGTG
PTPN6-LEPREL2chr127066948chr126948164217LRTLQVSPLDNARVRCTCCGTACCTTACAGGTCTCCCCGCTGGACAATGCTCGGGTGCGT
PTPN6-LEPREL2chr127066948chr126948164318RTLQVSPLDNARVRPCGTACCTTACAGGTCTCCCCGCTGGACAATGCTCGGGTGCGTCCT
PTPN6-LEPREL2chr127066948chr126948164419TLQVSPLDNARVRPRACCTTACAGGTCTCCCCGCTGGACAATGCTCGGGTGCGTCCTCGC

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Information of the samples that have these potential fusion neoantigens of PTPN6-LEPREL2

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
BLCAPTPN6-LEPREL2chr127066948ENST00000318974chr126948164ENST00000251761TCGA-FD-A3NA-01A

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Potential target of CAR-T therapy development for PTPN6-LEPREL2

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 PTPN6-LEPREL2

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 PTPN6-LEPREL2

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