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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:NAPEPLD-RELN

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NAPEPLD-RELN
FusionPDB ID: 57231
FusionGDB2.0 ID: 57231
HgeneTgene
Gene symbol

NAPEPLD

RELN

Gene ID

222236

5649

Gene nameN-acyl phosphatidylethanolamine phospholipase Dreelin
SynonymsC7orf18|FMP30|NAPE-PLDETL7|LIS2|PRO1598|RL
Cytomap

7q22.1

7q22.1

Type of geneprotein-codingprotein-coding
DescriptionN-acyl-phosphatidylethanolamine-hydrolyzing phospholipase DNAPE-hydrolyzing phospholipase Dreelin
Modification date2020031320200322
UniProtAcc

Q6IQ20

Main function of 5'-partner protein: FUNCTION: D-type phospholipase that hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce bioactive N-acylethanolamines/fatty acid ethanolamides (NAEs/FAEs) and phosphatidic acid (PubMed:14634025, PubMed:16527816, PubMed:27571266, PubMed:25684574). Cleaves the terminal phosphodiester bond of diacyl- and alkenylacyl-NAPEs, primarily playing a role in the generation of long-chain saturated and monounsaturated NAEs in the brain (By similarity). May control NAPE homeostasis in dopaminergic neuron membranes and regulate neuron survival, partly through RAC1 activation (By similarity). As a regulator of lipid metabolism in the adipose tissue, mediates the crosstalk between adipocytes, gut microbiota and immune cells to control body temperature and weight. In particular, regulates energy homeostasis by promoting cold-induced brown or beige adipocyte differentiation program to generate heat from fatty acids and glucose. Has limited D-type phospholipase activity toward N-acyl lyso-NAPEs (By similarity). {ECO:0000250|UniProtKB:Q8BH82, ECO:0000269|PubMed:14634025, ECO:0000269|PubMed:16527816, ECO:0000269|PubMed:25684574, ECO:0000269|PubMed:27571266}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000341533, ENST00000417955, 
ENST00000427257, ENST00000455523, 
ENST00000465647, 
ENST00000473945, 
ENST00000343529, ENST00000424685, 
ENST00000428762, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 3=9011 X 11 X 6=726
# samples 611
** MAII scorelog2(6/90*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/726*10)=-2.72246602447109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NAPEPLD [Title/Abstract] AND RELN [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NAPEPLD [Title/Abstract] AND RELN [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NAPEPLD(102768930)-RELN(103143677), # samples:3
Anticipated loss of major functional domain due to fusion event.NAPEPLD-RELN 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.
NAPEPLD-RELN 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.
NAPEPLD-RELN 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.
NAPEPLD-RELN 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.
NAPEPLD-RELN seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
NAPEPLD-RELN seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
NAPEPLD-RELN seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted 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
HgeneNAPEPLD

GO:0070292

N-acylphosphatidylethanolamine metabolic process

25684574



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/chr7:102768930/chr7:103143677)
- 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 NAPEPLD (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 RELN (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)
ENST00000341533NAPEPLDchr7102768930-ENST00000343529RELNchr7103143677-38637324382834798
ENST00000341533NAPEPLDchr7102768930-ENST00000428762RELNchr7103143677-38697324382840800
ENST00000341533NAPEPLDchr7102768930-ENST00000424685RELNchr7103143677-38697324382840800
ENST00000455523NAPEPLDchr7102768930-ENST00000343529RELNchr7103143677-3723592792694871
ENST00000455523NAPEPLDchr7102768930-ENST00000428762RELNchr7103143677-3729592792700873
ENST00000455523NAPEPLDchr7102768930-ENST00000424685RELNchr7103143677-3729592792700873

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
ENST00000341533ENST00000343529NAPEPLDchr7102768930-RELNchr7103143677-0.0005289510.999471
ENST00000341533ENST00000428762NAPEPLDchr7102768930-RELNchr7103143677-0.0005151420.9994848
ENST00000341533ENST00000424685NAPEPLDchr7102768930-RELNchr7103143677-0.0005282660.9994717
ENST00000455523ENST00000343529NAPEPLDchr7102768930-RELNchr7103143677-0.0001879510.99981207
ENST00000455523ENST00000428762NAPEPLDchr7102768930-RELNchr7103143677-0.0001870560.999813
ENST00000455523ENST00000424685NAPEPLDchr7102768930-RELNchr7103143677-0.0001876010.9998124

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 NAPEPLD-RELN

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NAPEPLDchr7102768930RELNchr7103143677592171MEKDHSSVPSSKEISVGCKVSEKIAQ
NAPEPLDchr7102768930RELNchr710314367773298MEKDHSSVPSSKEISVGCKVSEKIAQ

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Potential FusionNeoAntigen Information of NAPEPLD-RELN 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.
NAPEPLD-RELN_102768930_103143677.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)
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B45:01KEISVGCKV0.99590.68021120
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B50:02KEISVGCKV0.99210.54221120
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B35:04VPSSKEISV0.89350.9602716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B35:02VPSSKEISV0.89350.9602716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B35:03VPSSKEISV0.85950.912716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B52:01SSVPSSKEI0.78310.6241514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B47:01KEISVGCKV0.71670.54961120
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B41:01KEISVGCKV0.38370.73991120
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B50:01KEISVGCKV0.17950.69971120
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B39:13KEISVGCKV0.13260.86841120
NAPEPLD-RELNchr7102768930chr7103143677732HLA-A30:08SSKEISVGCK0.99630.6226919
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B38:01DHSSVPSSKEI0.99450.8476314
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B38:02DHSSVPSSKEI0.99430.8629314
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C01:17SVPSSKEI0.89740.8953614
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C01:30SVPSSKEI0.87850.9346614
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C03:07SSVPSSKEI0.99880.9838514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B40:06KEISVGCKV0.99840.52371120
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C15:06SSVPSSKEI0.99760.9081514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C03:19SSVPSSKEI0.99460.9864514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C03:08SSVPSSKEI0.99350.9162514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B51:07VPSSKEISV0.95180.5752716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B14:03VPSSKEISV0.89770.7807716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B35:12VPSSKEISV0.89350.9602716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C06:03SSVPSSKEI0.85770.9925514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C12:04SSVPSSKEI0.85220.9931514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B07:12VPSSKEISV0.84790.5206716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C12:12SSVPSSKEI0.73880.8793514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B39:10VPSSKEISV0.29060.9191716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C02:06SSVPSSKEI0.20870.9746514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C01:03SVPSSKEI0.94860.8659614
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C01:02SVPSSKEI0.92160.8866614
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C15:05SSVPSSKEI0.99740.9012514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C15:02SSVPSSKEI0.99720.8687514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C03:03SSVPSSKEI0.99350.9891514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C03:04SSVPSSKEI0.99350.9891514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C03:17SSVPSSKEI0.99340.9736514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C03:05SSVPSSKEI0.99330.9193514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B40:04KEISVGCKV0.99250.69541120
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C03:06SSVPSSKEI0.90060.989514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B35:09VPSSKEISV0.89350.9602716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B35:13VPSSKEISV0.86710.915716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C16:04SSVPSSKEI0.81720.9733514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C16:02SSVPSSKEI0.7680.9927514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C12:03SSVPSSKEI0.75340.9714514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B08:12VPSSKEISV0.73430.5403716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C16:01SSVPSSKEI0.59280.9733514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B67:01VPSSKEISV0.4570.7263716
NAPEPLD-RELNchr7102768930chr7103143677732HLA-C17:01SSVPSSKEI0.23120.87514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B50:05KEISVGCKV0.17950.69971120
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B50:04KEISVGCKV0.17950.69971120
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B07:13SSVPSSKEI0.00630.8608514
NAPEPLD-RELNchr7102768930chr7103143677732HLA-A30:01SSKEISVGCK0.99630.7817919
NAPEPLD-RELNchr7102768930chr7103143677732HLA-B38:05DHSSVPSSKEI0.99450.8476314

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Potential FusionNeoAntigen Information of NAPEPLD-RELN 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 NAPEPLD-RELN

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
9164SVPSSKEISVGCKVNAPEPLDRELNchr7102768930chr7103143677732

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NAPEPLD-RELN

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-B14:023BVN9164SVPSSKEISVGCKV-7.15543-7.26883
HLA-B14:023BVN9164SVPSSKEISVGCKV-4.77435-5.80965
HLA-B52:013W399164SVPSSKEISVGCKV-6.80875-6.92215
HLA-B52:013W399164SVPSSKEISVGCKV-4.20386-5.23916
HLA-A11:014UQ29164SVPSSKEISVGCKV-7.5194-8.5547
HLA-A11:014UQ29164SVPSSKEISVGCKV-6.9601-7.0735
HLA-A24:025HGA9164SVPSSKEISVGCKV-7.52403-7.63743
HLA-A24:025HGA9164SVPSSKEISVGCKV-5.82433-6.85963
HLA-B27:056PYJ9164SVPSSKEISVGCKV-3.28285-4.31815
HLA-B44:053DX89164SVPSSKEISVGCKV-5.91172-6.94702
HLA-B44:053DX89164SVPSSKEISVGCKV-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of NAPEPLD-RELN

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
NAPEPLD-RELNchr7102768930chr71031436771120KEISVGCKVAAAGAGATCTCAGTTGGATGTAAGGTG
NAPEPLD-RELNchr7102768930chr7103143677314DHSSVPSSKEIGATCACAGCAGTGTTCCAAGTTCTAAAGAGATC
NAPEPLD-RELNchr7102768930chr7103143677514SSVPSSKEIAGCAGTGTTCCAAGTTCTAAAGAGATC
NAPEPLD-RELNchr7102768930chr7103143677614SVPSSKEIAGTGTTCCAAGTTCTAAAGAGATC
NAPEPLD-RELNchr7102768930chr7103143677716VPSSKEISVGTTCCAAGTTCTAAAGAGATCTCAGTT
NAPEPLD-RELNchr7102768930chr7103143677919SSKEISVGCKAGTTCTAAAGAGATCTCAGTTGGATGTAAG

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 NAPEPLD-RELN

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
UCECNAPEPLD-RELNchr7102768930ENST00000341533chr7103143677ENST00000343529TCGA-AJ-A2QM-01A

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Potential target of CAR-T therapy development for NAPEPLD-RELN

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 NAPEPLD-RELN

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 NAPEPLD-RELN

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