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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:NEDD4L-SMAD2 (FusionGDB2 ID:58429)

Fusion Gene Summary for NEDD4L-SMAD2

check button Fusion gene summary
Fusion gene informationFusion gene name: NEDD4L-SMAD2
Fusion gene ID: 58429
HgeneTgene
Gene symbol

NEDD4L

SMAD2

Gene ID

23327

4087

Gene nameNEDD4 like E3 ubiquitin protein ligaseSMAD family member 2
SynonymsNEDD4-2|NEDD4.2|PVNH7|RSP5|hNEDD4-2JV18|JV18-1|MADH2|MADR2|hMAD-2|hSMAD2
Cytomap

18q21.31

18q21.1

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase NEDD4-likeHECT-type E3 ubiquitin transferase NED4Lneural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligaseubiquitin-protein ligase Rsp5mothers against decapentaplegic homolog 2MAD homolog 2SMAD, mothers against DPP homolog 2Sma- and Mad-related protein 2mother against DPP homolog 2
Modification date2020032920200322
UniProtAcc

Q96PU5

.
Ensembl transtripts involved in fusion geneENST00000256830, ENST00000356462, 
ENST00000382850, ENST00000400345, 
ENST00000589054, ENST00000256832, 
ENST00000357895, ENST00000431212, 
ENST00000435432, ENST00000456173, 
ENST00000456986, ENST00000586263, 
ENST00000588516, 		ENST00000587353, 
ENST00000591214, ENST00000262160, 
ENST00000356825, ENST00000402690, 
ENST00000586040, 
Fusion gene scores* DoF score28 X 18 X 11=554412 X 9 X 5=540
# samples 3512
** MAII scorelog2(35/5544*10)=-3.98550043030488
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(12/540*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: NEDD4L [Title/Abstract] AND SMAD2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointNEDD4L(55711940)-SMAD2(45368321), # samples:1
Anticipated loss of major functional domain due to fusion event.NEDD4L-SMAD2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NEDD4L-SMAD2 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
NEDD4L-SMAD2 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
NEDD4L-SMAD2 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
HgeneNEDD4L

GO:0003254

regulation of membrane depolarization

15217910

HgeneNEDD4L

GO:0006511

ubiquitin-dependent protein catabolic process

21463633

HgeneNEDD4L

GO:0010038

response to metal ion

11244092

HgeneNEDD4L

GO:0016567

protein ubiquitination

15217910|25631046

HgeneNEDD4L

GO:0034765

regulation of ion transmembrane transport

17289006

HgeneNEDD4L

GO:0042391

regulation of membrane potential

17289006

HgeneNEDD4L

GO:0043161

proteasome-mediated ubiquitin-dependent protein catabolic process

21463633

HgeneNEDD4L

GO:0060306

regulation of membrane repolarization

21463633

HgeneNEDD4L

GO:0070936

protein K48-linked ubiquitination

21463633

HgeneNEDD4L

GO:1901016

regulation of potassium ion transmembrane transporter activity

17289006

HgeneNEDD4L

GO:1901017

negative regulation of potassium ion transmembrane transporter activity

21463633

HgeneNEDD4L

GO:1901380

negative regulation of potassium ion transmembrane transport

21463633

HgeneNEDD4L

GO:1902306

negative regulation of sodium ion transmembrane transport

15217910

HgeneNEDD4L

GO:1903861

positive regulation of dendrite extension

23999003

HgeneNEDD4L

GO:2000009

negative regulation of protein localization to cell surface

21463633

HgeneNEDD4L

GO:2000650

negative regulation of sodium ion transmembrane transporter activity

15217910

TgeneSMAD2

GO:0007179

transforming growth factor beta receptor signaling pathway

8752209|9389648|9732876|18548003

TgeneSMAD2

GO:0007182

common-partner SMAD protein phosphorylation

16806156

TgeneSMAD2

GO:0007183

SMAD protein complex assembly

9111321

TgeneSMAD2

GO:0045893

positive regulation of transcription, DNA-templated

9311995|9389648|9732876

TgeneSMAD2

GO:0045944

positive regulation of transcription by RNA polymerase II

9389648

TgeneSMAD2

GO:0070723

response to cholesterol

17878231


check buttonFusion gene breakpoints across NEDD4L (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonFusion gene breakpoints across SMAD2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4STADTCGA-RD-A8MWNEDD4Lchr18

55711940

+SMAD2chr18

45368321

-


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Fusion Gene ORF analysis for NEDD4L-SMAD2

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5CDS-intronENST00000256830ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5CDS-intronENST00000256830ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5CDS-intronENST00000356462ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5CDS-intronENST00000356462ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5CDS-intronENST00000382850ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5CDS-intronENST00000382850ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5CDS-intronENST00000400345ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5CDS-intronENST00000400345ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5CDS-intronENST00000589054ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5CDS-intronENST00000589054ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5UTR-3CDSENST00000256832ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5UTR-3CDSENST00000256832ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5UTR-3CDSENST00000256832ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5UTR-3CDSENST00000256832ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5UTR-intronENST00000256832ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
5UTR-intronENST00000256832ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000256830ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000256830ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000256830ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000256830ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000356462ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000356462ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000356462ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000356462ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000382850ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000382850ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000382850ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000382850ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000400345ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000400345ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000400345ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000400345ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000589054ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000589054ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000589054ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
Frame-shiftENST00000589054ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000357895ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000357895ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000357895ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000357895ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000431212ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000431212ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000431212ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000431212ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000435432ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000435432ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000435432ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000435432ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000456173ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000456173ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000456173ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000456173ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000456986ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000456986ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000456986ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000456986ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000586263ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000586263ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000586263ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000586263ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000588516ENST00000262160NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000588516ENST00000356825NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000588516ENST00000402690NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-3CDSENST00000588516ENST00000586040NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000357895ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000357895ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000431212ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000431212ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000435432ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000435432ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000456173ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000456173ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000456986ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000456986ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000586263ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000586263ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000588516ENST00000587353NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-
intron-intronENST00000588516ENST00000591214NEDD4Lchr18

55711940

+SMAD2chr18

45368321

-

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

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

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Fusion Genomic Features for NEDD4L-SMAD2


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for NEDD4L-SMAD2


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/:55711940/:45368321)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
NEDD4L

Q96PU5

.
FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338). {ECO:0000250|UniProtKB:Q8CFI0, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15489223, ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:15576372, ECO:0000269|PubMed:19144635, ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27694961}.FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page


* Minus value of BPloci means that the break pointn is located before the CDS.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for NEDD4L-SMAD2


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for NEDD4L-SMAD2


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for NEDD4L-SMAD2


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for NEDD4L-SMAD2


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource