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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:NVL-NEK2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NVL-NEK2
FusionPDB ID: 61188
FusionGDB2.0 ID: 61188
HgeneTgene
Gene symbol

NVL

NEK2

Gene ID

4931

4751

Gene namenuclear VCP likeNIMA related kinase 2
SynonymsNVL2HsPK21|NEK2A|NLK1|PPP1R111|RP67
Cytomap

1q42.11

1q32.3

Type of geneprotein-codingprotein-coding
Descriptionnuclear valosin-containing protein-likeNVLpserine/threonine-protein kinase Nek2NIMA (never in mitosis gene a)-related kinase 2nimA-like protein kinase 1nimA-related protein kinase 2protein phosphatase 1, regulatory subunit 111
Modification date2020031320200313
UniProtAcc.

P51955

Main function of 5'-partner protein: FUNCTION: Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143). Involved in the regulation of centrosome disjunction (PubMed:26220856). {ECO:0000269|PubMed:11742531, ECO:0000269|PubMed:12857871, ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:15358203, ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18297113, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:26220856}.; FUNCTION: [Isoform 1]: Phosphorylates and activates NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}.; FUNCTION: [Isoform 2]: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}.
Ensembl transtripts involved in fusion geneENST idsENST00000361463, ENST00000281701, 
ENST00000340871, ENST00000391875, 
ENST00000469075, ENST00000482491, 
ENST00000468673, 
ENST00000366999, 
ENST00000540251, ENST00000366998, 
ENST00000462283, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 11 X 8=9683 X 4 X 3=36
# samples 124
** MAII scorelog2(12/968*10)=-3.01197264166608
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: NVL [Title/Abstract] AND NEK2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NVL [Title/Abstract] AND NEK2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NVL(224437914)-NEK2(211847855), # samples:3
Anticipated loss of major functional domain due to fusion event.NVL-NEK2 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.
NVL-NEK2 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.
NVL-NEK2 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.
NVL-NEK2 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.
NVL-NEK2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NVL-NEK2 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
NVL-NEK2 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
NVL-NEK2 seems lost the major protein functional domain in Tgene partner, which is a kinase 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
HgeneNVL

GO:0006364

rRNA processing

29107693

HgeneNVL

GO:0032092

positive regulation of protein binding

29107693

HgeneNVL

GO:0042273

ribosomal large subunit biogenesis

26166824

HgeneNVL

GO:1904749

regulation of protein localization to nucleolus

29107693

TgeneNEK2

GO:0006468

protein phosphorylation

21076410

TgeneNEK2

GO:0007059

chromosome segregation

14978040

TgeneNEK2

GO:0046777

protein autophosphorylation

17626005

TgeneNEK2

GO:0051299

centrosome separation

18086858



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/chr1:224437914/chr1:211847855)
- 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 NVL (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 NEK2 (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)
ENST00000391875NVLchr1224437914-ENST00000366999NEK2chr1211847855-415422585634991147
ENST00000281701NVLchr1224437914-ENST00000366999NEK2chr1211847855-4445254922437901188
ENST00000469075NVLchr1224437914-ENST00000366999NEK2chr1211847855-392320271132681085
ENST00000391875NVLchr1224437913-ENST00000366999NEK2chr1211847855-415422585634991147
ENST00000281701NVLchr1224437913-ENST00000366999NEK2chr1211847855-4445254922437901188
ENST00000469075NVLchr1224437913-ENST00000366999NEK2chr1211847855-392320271132681085

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
ENST00000391875ENST00000366999NVLchr1224437914-NEK2chr1211847855-0.0002621490.9997378
ENST00000281701ENST00000366999NVLchr1224437914-NEK2chr1211847855-0.0002301010.99976987
ENST00000469075ENST00000366999NVLchr1224437914-NEK2chr1211847855-0.0002870450.9997129
ENST00000391875ENST00000366999NVLchr1224437913-NEK2chr1211847855-0.0002621490.9997378
ENST00000281701ENST00000366999NVLchr1224437913-NEK2chr1211847855-0.0002301010.99976987
ENST00000469075ENST00000366999NVLchr1224437913-NEK2chr1211847855-0.0002870450.9997129

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 NVL-NEK2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NVLchr1224437913NEK2chr12118478552027672PADRLAILKTITKILVWKELDYGSMT
NVLchr1224437913NEK2chr12118478552258734PADRLAILKTITKILVWKELDYGSMT
NVLchr1224437913NEK2chr12118478552549775PADRLAILKTITKILVWKELDYGSMT
NVLchr1224437914NEK2chr12118478552027672PADRLAILKTITKILVWKELDYGSMT
NVLchr1224437914NEK2chr12118478552258734PADRLAILKTITKILVWKELDYGSMT
NVLchr1224437914NEK2chr12118478552549775PADRLAILKTITKILVWKELDYGSMT

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Potential FusionNeoAntigen Information of NVL-NEK2 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.
NVL-NEK2_224437913_211847855.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)
NVL-NEK2chr1224437913chr12118478552549HLA-B57:01TITKILVW0.99940.96917
NVL-NEK2chr1224437913chr12118478552549HLA-B58:01TITKILVW0.99660.8884917
NVL-NEK2chr1224437913chr12118478552549HLA-B57:01KTITKILVW0.99990.9703817
NVL-NEK2chr1224437913chr12118478552549HLA-B58:02KTITKILVW0.99960.9422817
NVL-NEK2chr1224437913chr12118478552549HLA-B58:01KTITKILVW0.99950.9079817
NVL-NEK2chr1224437913chr12118478552549HLA-B57:03KTITKILVW0.99880.9667817
NVL-NEK2chr1224437913chr12118478552549HLA-B15:17KTITKILVW0.99840.8809817
NVL-NEK2chr1224437913chr12118478552549HLA-A32:13KTITKILVW0.99720.9578817
NVL-NEK2chr1224437913chr12118478552549HLA-B15:16KTITKILVW0.9960.7813817
NVL-NEK2chr1224437913chr12118478552549HLA-B52:01AILKTITKI0.21150.5791514
NVL-NEK2chr1224437913chr12118478552549HLA-B13:01AILKTITKI0.10.8387514
NVL-NEK2chr1224437913chr12118478552549HLA-B57:01LKTITKILVW0.99870.9696717
NVL-NEK2chr1224437913chr12118478552549HLA-A30:08KTITKILVWK0.99820.5816818
NVL-NEK2chr1224437913chr12118478552549HLA-B58:02LKTITKILVW0.99390.9507717
NVL-NEK2chr1224437913chr12118478552549HLA-B58:01LKTITKILVW0.98610.922717
NVL-NEK2chr1224437913chr12118478552549HLA-B57:03LKTITKILVW0.97650.9715717
NVL-NEK2chr1224437913chr12118478552549HLA-B57:01KTITKILVWK0.78870.8955818
NVL-NEK2chr1224437913chr12118478552549HLA-B57:01ILKTITKILVW0.9990.9485617
NVL-NEK2chr1224437913chr12118478552549HLA-B58:02ILKTITKILVW0.99710.9207617
NVL-NEK2chr1224437913chr12118478552549HLA-B58:01ILKTITKILVW0.98490.8776617
NVL-NEK2chr1224437913chr12118478552549HLA-B57:03ILKTITKILVW0.98440.9462617
NVL-NEK2chr1224437913chr12118478552549HLA-B15:04ILKTITKIL0.91320.701615
NVL-NEK2chr1224437913chr12118478552549HLA-C15:04KTITKILVW0.85230.9199817
NVL-NEK2chr1224437913chr12118478552549HLA-C12:04KTITKILVW0.27640.9966817
NVL-NEK2chr1224437913chr12118478552549HLA-C15:02KTITKILV0.99990.8535816
NVL-NEK2chr1224437913chr12118478552549HLA-B57:10TITKILVW0.99940.96917
NVL-NEK2chr1224437913chr12118478552549HLA-B57:10KTITKILVW0.99990.9703817
NVL-NEK2chr1224437913chr12118478552549HLA-B57:04KTITKILVW0.99950.7049817
NVL-NEK2chr1224437913chr12118478552549HLA-B58:06KTITKILVW0.99910.8366817
NVL-NEK2chr1224437913chr12118478552549HLA-A32:01KTITKILVW0.99910.9703817
NVL-NEK2chr1224437913chr12118478552549HLA-B57:02KTITKILVW0.99510.836817
NVL-NEK2chr1224437913chr12118478552549HLA-B15:13KTITKILVW0.98330.6871817
NVL-NEK2chr1224437913chr12118478552549HLA-A32:01AILKTITKI0.97910.9079514
NVL-NEK2chr1224437913chr12118478552549HLA-B15:24KTITKILVW0.87060.9321817
NVL-NEK2chr1224437913chr12118478552549HLA-C15:09KTITKILVW0.85230.9199817
NVL-NEK2chr1224437913chr12118478552549HLA-B15:30ILKTITKIL0.73290.5728615
NVL-NEK2chr1224437913chr12118478552549HLA-A25:01KTITKILVW0.33450.8808817
NVL-NEK2chr1224437913chr12118478552549HLA-B57:10LKTITKILVW0.99870.9696717
NVL-NEK2chr1224437913chr12118478552549HLA-A30:01KTITKILVWK0.99820.7661818
NVL-NEK2chr1224437913chr12118478552549HLA-B57:04LKTITKILVW0.99320.7072717
NVL-NEK2chr1224437913chr12118478552549HLA-B58:06LKTITKILVW0.98380.866717
NVL-NEK2chr1224437913chr12118478552549HLA-B57:02LKTITKILVW0.95330.9086717
NVL-NEK2chr1224437913chr12118478552549HLA-B57:10KTITKILVWK0.78870.8955818
NVL-NEK2chr1224437913chr12118478552549HLA-B57:10ILKTITKILVW0.9990.9485617
NVL-NEK2chr1224437913chr12118478552549HLA-B57:04ILKTITKILVW0.99740.6804617
NVL-NEK2chr1224437913chr12118478552549HLA-B58:06ILKTITKILVW0.99740.8005617

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Potential FusionNeoAntigen Information of NVL-NEK2 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 NVL-NEK2

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
3797ILKTITKILVWKELNVLNEK2chr1224437913chr12118478552549

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NVL-NEK2

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-B14:023BVN3797ILKTITKILVWKEL-7.9962-8.1096
HLA-B14:023BVN3797ILKTITKILVWKEL-5.70842-6.74372
HLA-B52:013W393797ILKTITKILVWKEL-6.83737-6.95077
HLA-B52:013W393797ILKTITKILVWKEL-4.4836-5.5189
HLA-A11:014UQ23797ILKTITKILVWKEL-10.0067-10.1201
HLA-A11:014UQ23797ILKTITKILVWKEL-9.03915-10.0745
HLA-A24:025HGA3797ILKTITKILVWKEL-6.56204-6.67544
HLA-A24:025HGA3797ILKTITKILVWKEL-5.42271-6.45801
HLA-B44:053DX83797ILKTITKILVWKEL-7.85648-8.89178
HLA-B44:053DX83797ILKTITKILVWKEL-5.3978-5.5112
HLA-A02:016TDR3797ILKTITKILVWKEL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NVL-NEK2

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
NVL-NEK2chr1224437913chr1211847855514AILKTITKIGCCATCTTAAAAACTATCACAAAAATA
NVL-NEK2chr1224437913chr1211847855615ILKTITKILATCTTAAAAACTATCACAAAAATATTA
NVL-NEK2chr1224437913chr1211847855617ILKTITKILVWATCTTAAAAACTATCACAAAAATATTAGTTTGG
NVL-NEK2chr1224437913chr1211847855717LKTITKILVWTTAAAAACTATCACAAAAATATTAGTTTGG
NVL-NEK2chr1224437913chr1211847855816KTITKILVAAAACTATCACAAAAATATTAGTT
NVL-NEK2chr1224437913chr1211847855817KTITKILVWAAAACTATCACAAAAATATTAGTTTGG
NVL-NEK2chr1224437913chr1211847855818KTITKILVWKAAAACTATCACAAAAATATTAGTTTGGAAA
NVL-NEK2chr1224437913chr1211847855917TITKILVWACTATCACAAAAATATTAGTTTGG

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 NVL-NEK2

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
BRCANVL-NEK2chr1224437913ENST00000281701chr1211847855ENST00000366999TCGA-A8-A09Q

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Potential target of CAR-T therapy development for NVL-NEK2

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 NVL-NEK2

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 NVL-NEK2

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