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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein Structure
	pLDDT scores
	Ramachandran Plot of Fusion Protein Structure
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:NFE2L2-PDE11A

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: NFE2L2-PDE11A
	FusionPDB ID: 58845
	FusionGDB2.0 ID: 58845
		Hgene	Tgene
	Gene symbol	NFE2L2	PDE11A
	Gene ID	4780	50940
	Gene name	nuclear factor, erythroid 2 like 2	phosphodiesterase 11A
	Synonyms	HEBP1\|IMDDHH\|NRF2\|Nrf-2	PPNAD2
	Cytomap	2q31.2	2q31.2
	Type of gene	protein-coding	protein-coding
	Description	nuclear factor erythroid 2-related factor 2nuclear factor erythroid-derived 2-like 2	dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11AcAMP and cGMP cyclic nucleotide phosphodiesterase 11A
	Modification date	20200329	20200313
	UniProtAcc	Q16236	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000397062, ENST00000397063, ENST00000446151, ENST00000464747, ENST00000423513,	ENST00000497003, ENST00000389683, ENST00000409504, ENST00000449286, ENST00000450799, ENST00000286063, ENST00000358450,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	18 X 18 X 9=2916	8 X 5 X 6=240
	# samples	29	11
	** MAII score	log2(29/2916*10)=-3.329865914312 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(11/240*10)=-1.12553088208386 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: NFE2L2 [Title/Abstract] AND PDE11A [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	NFE2L2(178097120)-PDE11A(178634101), # samples:2
Anticipated loss of major functional domain due to fusion event.	NFE2L2-PDE11A 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. NFE2L2-PDE11A 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. NFE2L2-PDE11A 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. NFE2L2-PDE11A 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. NFE2L2-PDE11A seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. NFE2L2-PDE11A seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. NFE2L2-PDE11A seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF. NFE2L2-PDE11A seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF. NFE2L2-PDE11A seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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)

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	NFE2L2	GO:0010499	proteasomal ubiquitin-independent protein catabolic process	19424503
Hgene	NFE2L2	GO:0016567	protein ubiquitination	15983046
Hgene	NFE2L2	GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	15983046
Hgene	NFE2L2	GO:0045944	positive regulation of transcription by RNA polymerase II	17015834
Hgene	NFE2L2	GO:0071498	cellular response to fluid shear stress	25190803

Fusion gene breakpoints across NFE2L2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across PDE11A (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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Fusion Gene Sample Information

Fusion gene information from FusionGDB2.0.

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.

Source	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	LUSC	TCGA-18-4721-01A	NFE2L2	chr2	178097120	-	PDE11A	chr2	178634101	-
ChimerDB4	LUSC	TCGA-18-4721	NFE2L2	chr2	178097120	-	PDE11A	chr2	178634101	-
ChimerDB4	OV	TCGA-61-1724-01A	NFE2L2	chr2	178128131	-	PDE11A	chr2	178705110	-
ChimerDB4	OV	TCGA-61-1724-01A	NFE2L2	chr2	178129260	-	PDE11A	chr2	178705110	-
ChimerDB4	OV	TCGA-61-1724	NFE2L2	chr2	178128130	-	PDE11A	chr2	178705110	-
ChimerDB4	OV	TCGA-61-1724	NFE2L2	chr2	178129259	-	PDE11A	chr2	178705110	-

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Fusion ORF Analysis

Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	Seq length (transcript)	BP loci (transcript)	Predicted start (transcript)	Predicted stop (transcript)	Seq length (amino acids)
ENST00000397062	NFE2L2	chr2	178097120	-	ENST00000286063	PDE11A	chr2	178634101	-	8369	1149	555	2213	552
ENST00000397062	NFE2L2	chr2	178097120	-	ENST00000358450	PDE11A	chr2	178634101	-	3552	1149	555	2213	552

DeepORF 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.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	No-coding score	Coding score
ENST00000397062	ENST00000286063	NFE2L2	chr2	178097120	-	PDE11A	chr2	178634101	-	0.000255669	0.99974436
ENST00000397062	ENST00000358450	NFE2L2	chr2	178097120	-	PDE11A	chr2	178634101	-	0.000935549	0.9990645

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Fusion Amino Acid Sequences

For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>58845_58845_1_NFE2L2-PDE11A_NFE2L2_chr2_178097120_ENST00000397062_PDE11A_chr2_178634101_ENST00000286063_length(amino acids)=552AA_BP=197
MMDLELPPPGLPSQQDMDLIDILWRQDIDLGVSREVFDFSQRRKEYELEKQKKLEKERQEQLQKEQEKAFFAQLQLDEETGEFLPIQPAQ
HIQSETSGSANYSQVAHIPKSDALYFDDCMQLLAQTFPFVDDNEVSSATFQSLVPDIPGHIESPVFIATNQAQSPETSVAQVAPVDLDGM
QQDIEQVWEELLSIPELQVLSYHATCSKAEVDKFKAANIPLVSELAIDDIHFDDFSLDVDAMITAALRMFMELGMVQKFKIDYETLCRWL
LTVRKNYRMVLYHNWRHAFNVCQLMFAMLTTAGFQDILTEVEILAVIVGCLCHDLDHRGTNNAFQAKSGSALAQLYGTSATLEHHHFNHA
VMILQSEGHNIFANLSSKEYSDLMQLLKQSILATDLTLYFERRTEFFELVSKGEYDWNIKNHRDIFRSMLMTACDLGAVTKPWEISRQVA
ELVTSEFFEQGDRERLELKLTPSAIFDRNRKDELPRLQLEWIDSICMPLYQALVKVNVKLKPMLDSVATNRSKWEELHQKRLLASTASSS

--------------------------------------------------------------

>58845_58845_2_NFE2L2-PDE11A_NFE2L2_chr2_178097120_ENST00000397062_PDE11A_chr2_178634101_ENST00000358450_length(amino acids)=552AA_BP=197
MMDLELPPPGLPSQQDMDLIDILWRQDIDLGVSREVFDFSQRRKEYELEKQKKLEKERQEQLQKEQEKAFFAQLQLDEETGEFLPIQPAQ
HIQSETSGSANYSQVAHIPKSDALYFDDCMQLLAQTFPFVDDNEVSSATFQSLVPDIPGHIESPVFIATNQAQSPETSVAQVAPVDLDGM
QQDIEQVWEELLSIPELQVLSYHATCSKAEVDKFKAANIPLVSELAIDDIHFDDFSLDVDAMITAALRMFMELGMVQKFKIDYETLCRWL
LTVRKNYRMVLYHNWRHAFNVCQLMFAMLTTAGFQDILTEVEILAVIVGCLCHDLDHRGTNNAFQAKSGSALAQLYGTSATLEHHHFNHA
VMILQSEGHNIFANLSSKEYSDLMQLLKQSILATDLTLYFERRTEFFELVSKGEYDWNIKNHRDIFRSMLMTACDLGAVTKPWEISRQVA
ELVTSEFFEQGDRERLELKLTPSAIFDRNRKDELPRLQLEWIDSICMPLYQALVKVNVKLKPMLDSVATNRSKWEELHQKRLLASTASSS

--------------------------------------------------------------

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Fusion Protein Functional Features

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr2:178097120/chr2:178634101)
- 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.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
NFE2L2 Q16236	.
FUNCTION: Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles (PubMed:11035812, PubMed:19489739, PubMed:29018201, PubMed:31398338). In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex (PubMed:11035812, PubMed:15601839, PubMed:29018201). In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerization with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes (PubMed:19489739, PubMed:29590092). The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes (PubMed:20452972). May also be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region (PubMed:7937919). {ECO:0000269\|PubMed:11035812, ECO:0000269\|PubMed:15601839, ECO:0000269\|PubMed:19489739, ECO:0000269\|PubMed:20452972, ECO:0000269\|PubMed:29018201, ECO:0000269\|PubMed:29590092, ECO:0000269\|PubMed:31398338, ECO:0000269\|PubMed:7937919}.	FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

Retention 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.

- Retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000397062

29_31

198.0

606.0

Motif

DLG motif

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000397063

29_31

182.0

590.0

Motif

DLG motif

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000446151

29_31

175.0

583.0

Motif

DLG motif

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000464747

29_31

182.0

590.0

Motif

DLG motif

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000286063

588_912

579.0

934.0

Domain

PDEase

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000358450

402_558

329.0

684.0

Domain

Note=GAF 2

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000358450

588_912

329.0

684.0

Domain

PDEase

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000389683

217_370

135.0

490.0

Domain

Note=GAF 1

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000389683

402_558

135.0

490.0

Domain

Note=GAF 2

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000389683

588_912

135.0

490.0

Domain

PDEase

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000409504

402_558

221.0

663.0

Domain

Note=GAF 2

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000409504

588_912

221.0

663.0

Domain

PDEase

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000449286

402_558

221.0

576.0

Domain

Note=GAF 2

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000449286

588_912

221.0

576.0

Domain

PDEase

- Not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000397062

497_560

198.0

606.0

Domain

bZIP

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000397063

497_560

182.0

590.0

Domain

bZIP

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000446151

497_560

175.0

583.0

Domain

bZIP

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000464747

497_560

182.0

590.0

Domain

bZIP

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000397062

499_518

198.0

606.0

Region

Basic motif

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000397062

522_529

198.0

606.0

Region

Leucine-zipper

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000397063

499_518

182.0

590.0

Region

Basic motif

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000397063

522_529

182.0

590.0

Region

Leucine-zipper

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000446151

499_518

175.0

583.0

Region

Basic motif

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000446151

522_529

175.0

583.0

Region

Leucine-zipper

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000464747

499_518

182.0

590.0

Region

Basic motif

Hgene

NFE2L2

chr2:178097120

chr2:178634101

ENST00000464747

522_529

182.0

590.0

Region

Leucine-zipper

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000286063

217_370

579.0

934.0

Domain

Note=GAF 1

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000286063

402_558

579.0

934.0

Domain

Note=GAF 2

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000358450

217_370

329.0

684.0

Domain

Note=GAF 1

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000409504

217_370

221.0

663.0

Domain

Note=GAF 1

Tgene

PDE11A

chr2:178097120

chr2:178634101

ENST00000449286

217_370

221.0

576.0

Domain

Note=GAF 1

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Fusion Protein Structures

PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

Fusion protein PDB link (fusion AA seq ID in FusionPDB)	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	AA seq	Len(AA seq)
PDB file >>>1182_NFE2L2_178097120_PDE11A_178634101_1182_NFE2L2_178097120_PDE11A_178634101_ranked_0.pdb	NFE2L2	178097120	178097120	ENST00000358450	PDE11A	chr2	178634101	-	MMDLELPPPGLPSQQDMDLIDILWRQDIDLGVSREVFDFSQRRKEYELEKQKKLEKERQEQLQKEQEKAFFAQLQLDEETGEFLPIQPAQ HIQSETSGSANYSQVAHIPKSDALYFDDCMQLLAQTFPFVDDNEVSSATFQSLVPDIPGHIESPVFIATNQAQSPETSVAQVAPVDLDGM QQDIEQVWEELLSIPELQVLSYHATCSKAEVDKFKAANIPLVSELAIDDIHFDDFSLDVDAMITAALRMFMELGMVQKFKIDYETLCRWL LTVRKNYRMVLYHNWRHAFNVCQLMFAMLTTAGFQDILTEVEILAVIVGCLCHDLDHRGTNNAFQAKSGSALAQLYGTSATLEHHHFNHA VMILQSEGHNIFANLSSKEYSDLMQLLKQSILATDLTLYFERRTEFFELVSKGEYDWNIKNHRDIFRSMLMTACDLGAVTKPWEISRQVA ELVTSEFFEQGDRERLELKLTPSAIFDRNRKDELPRLQLEWIDSICMPLYQALVKVNVKLKPMLDSVATNRSKWEELHQKRLLASTASSS	552

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pLDDT score distribution

pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

NFE2L2_pLDDT.png

PDE11A_pLDDT.png

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

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Ramachandran Plot of Fusion Protein Structure

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

Fusion AA seq ID in FusionPDB and their Ramachandran plots

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Fusion Protein-Protein Interaction

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)

Gene

PPI interactors

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
NFE2L2
PDE11A

- Retained interactions in fusion protein (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost interactions due to fusion (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs to NFE2L2-PDE11A

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

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Related Diseases to NFE2L2-PDE11A

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source