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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:ZNF440-ECSIT

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: ZNF440-ECSIT
	FusionPDB ID: 102129
	FusionGDB2.0 ID: 102129
		Hgene	Tgene
	Gene symbol	ZNF440	ECSIT
	Gene ID	126070	51295
	Gene name	zinc finger protein 440	ECSIT signaling integrator
	Synonyms	-	SITPEC
	Cytomap	19p13.2	19p13.2
	Type of gene	protein-coding	protein-coding
	Description	zinc finger protein 440	evolutionarily conserved signaling intermediate in Toll pathway, mitochondrialECSIT homologECSIT signalling integratorlikely ortholog of mouse signaling intermediate in Toll pathway evolutionarily conserved
	Modification date	20200313	20200313
	UniProtAcc	.	Q9BQ95
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000304060,	ENST00000252440, ENST00000270517, ENST00000417981, ENST00000588998, ENST00000591104, ENST00000591352, ENST00000592312,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	3 X 2 X 4=24	6 X 5 X 5=150
	# samples	4	8
	** MAII score	log2(4/24*10)=0.736965594166206 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0	log2(8/150*10)=-0.906890595608519 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: ZNF440 [Title/Abstract] AND ECSIT [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	ZNF440(11925265)-ECSIT(11618863), # samples:2
Anticipated loss of major functional domain due to fusion event.	ZNF440-ECSIT 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. ZNF440-ECSIT 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)

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
Tgene	ECSIT	GO:0051341	regulation of oxidoreductase activity	17344420
Tgene	ECSIT	GO:0061635	regulation of protein complex stability	17344420

Fusion gene breakpoints across ZNF440 (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 ECSIT (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	UVM	TCGA-VD-AA8M-01A	ZNF440	chr19	11925265	+	ECSIT	chr19	11618863	-
ChimerDB4	UVM	TCGA-VD-AA8M	ZNF440	chr19	11925265	+	ECSIT	chr19	11618863	-
ChiTaRS5.0	N/A	BG222450	ZNF440	chr19	11945695	-	ECSIT	chr19	11633709	-

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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)
ENST00000304060	ZNF440	chr19	11925265	+	ENST00000270517	ECSIT	chr19	11618863	-	993	167	811	185	208
ENST00000304060	ZNF440	chr19	11925265	+	ENST00000588998	ECSIT	chr19	11618863	-	831	167	662	108	184
ENST00000304060	ZNF440	chr19	11925265	+	ENST00000252440	ECSIT	chr19	11618863	-	831	167	662	108	184
ENST00000304060	ZNF440	chr19	11925265	+	ENST00000417981	ECSIT	chr19	11618863	-	907	167	164	724	186
ENST00000304060	ZNF440	chr19	11925265	+	ENST00000591104	ECSIT	chr19	11618863	-	604	167	597	1	199
ENST00000304060	ZNF440	chr19	11925265	+	ENST00000592312	ECSIT	chr19	11618863	-	748	167	726	1	242

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
ENST00000304060	ENST00000270517	ZNF440	chr19	11925265	+	ECSIT	chr19	11618863	-	0.004624309	0.99537563
ENST00000304060	ENST00000588998	ZNF440	chr19	11925265	+	ECSIT	chr19	11618863	-	0.18096285	0.81903714
ENST00000304060	ENST00000252440	ZNF440	chr19	11925265	+	ECSIT	chr19	11618863	-	0.18096285	0.81903714
ENST00000304060	ENST00000417981	ZNF440	chr19	11925265	+	ECSIT	chr19	11618863	-	0.003748586	0.9962514
ENST00000304060	ENST00000591104	ZNF440	chr19	11925265	+	ECSIT	chr19	11618863	-	0.01805827	0.9819417
ENST00000304060	ENST00000592312	ZNF440	chr19	11925265	+	ECSIT	chr19	11618863	-	0.42354518	0.5764549

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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

>102129_102129_1_ZNF440-ECSIT_ZNF440_chr19_11925265_ENST00000304060_ECSIT_chr19_11618863_ENST00000252440_length(amino acids)=184AA_BP=1
MICCTLKGHLMPSVHRLLGPQPVPSRRLRLALALLLSLQVVVFFLVVLGQGRLLQPCRGCLELPGGPGEAEDHGDLGQGWVGLLQALDPL
SHRRLVMSTRHAHGEDRAFLHFIDVKLVVVPATPHILQVQLHRVVEVPLLRRLFHFLRCGAGGDLLHLLSLWAKEPFLGFQGVPASSAWL

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

>102129_102129_2_ZNF440-ECSIT_ZNF440_chr19_11925265_ENST00000304060_ECSIT_chr19_11618863_ENST00000270517_length(amino acids)=208AA_BP=
MICCTLKGHLMPSVHRLLGPQPVPSRRLRLALALLLSLQVVVFFLVVLGQGRLLQPCRGCLELPGGPGEAEDHGDLGQGWVGLLQALDPL
SHRRLVMSTRHAHGEDRAFLHFIDVKLVVVPATPHILQVQLHRVVEVPLLRRLFHFPLLRGQQVSSEDVVIHTLVAEPQGEGALNKDRPG

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

>102129_102129_3_ZNF440-ECSIT_ZNF440_chr19_11925265_ENST00000304060_ECSIT_chr19_11618863_ENST00000417981_length(amino acids)=186AA_BP=1
MVPLPKDSTGAADPPQPHIVGIQSPDQQAALARHNPARPVFVEGPFSLWLRNKCVYYHILRADLLPPEEREVEETPEEWNLYYPMQLDLE
YVRSGWDNYEFDINEVEEGPVFAMCMAGAHDQATMAKWIQGLQETNPTLAQIPVVFRLAGSTRELQTSSAGLEEPPLPEDHQEEDDNLQR

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

>102129_102129_4_ZNF440-ECSIT_ZNF440_chr19_11925265_ENST00000304060_ECSIT_chr19_11618863_ENST00000588998_length(amino acids)=184AA_BP=1
MICCTLKGHLMPSVHRLLGPQPVPSRRLRLALALLLSLQVVVFFLVVLGQGRLLQPCRGCLELPGGPGEAEDHGDLGQGWVGLLQALDPL
SHRRLVMSTRHAHGEDRAFLHFIDVKLVVVPATPHILQVQLHRVVEVPLLRRLFHFLRCGAGGDLLHLLSLWAKEPFLGFQGVPASSAWL

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

>102129_102129_5_ZNF440-ECSIT_ZNF440_chr19_11925265_ENST00000304060_ECSIT_chr19_11618863_ENST00000591104_length(amino acids)=199AA_BP=1
MALLLSLQVVVFFLVVLGQGRLLQPCRGCLELPGGPGEAEDHGDLGQGWVGLLQALDPLSHRRLVMSTRHAHGEDRAFLHFIDVKLVVVP
ATPHILQVQLHRVVEVPLLRRLFHFPLLRGQQVSSTMWGWGGSAAPVESLGKGTISRLPGCSGVLCVAPATSVGHSAGYRATEALVEAPS

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

>102129_102129_6_ZNF440-ECSIT_ZNF440_chr19_11925265_ENST00000304060_ECSIT_chr19_11618863_ENST00000592312_length(amino acids)=242AA_BP=1
MGQGWVGLLQALDPLSHRRLVMSTRHAHGEDRAFLHFIDVKLVVVPATPHILQVQLHRVVEVPLLRRLFHFPLLRGQQVSSEDVVIHTLV
AEPQGEGALNKDRPGWIVAGQGGLLIGTLDSWCGDIHALCPARDSAQRPREPSLGPARTWQGLGKVRDLAAPMLSDLPTMWGWGGSAAPV

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

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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/chr19:11925265/chr19:11618863)
- 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
.	ECSIT Q9BQ95
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.	FUNCTION: Adapter protein of the Toll-like and IL-1 receptor signaling pathway that is involved in the activation of NF-kappa-B via MAP3K1. Promotes proteolytic activation of MAP3K1. Involved in the BMP signaling pathway. Required for normal embryonic development (By similarity). {ECO:0000250}.; FUNCTION: Required for efficient assembly of mitochondrial NADH:ubiquinone oxidoreductase.

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

- 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

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

4_86

1.0

596.0

Domain

KRAB

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

144_166

1.0

596.0

Zinc finger

C2H2-type 1%3B degenerate

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

172_194

1.0

596.0

Zinc finger

C2H2-type 2

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

200_222

1.0

596.0

Zinc finger

C2H2-type 3

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

228_250

1.0

596.0

Zinc finger

C2H2-type 4

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

256_278

1.0

596.0

Zinc finger

C2H2-type 5%3B degenerate

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

284_306

1.0

596.0

Zinc finger

C2H2-type 6

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

312_334

1.0

596.0

Zinc finger

C2H2-type 7

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

340_362

1.0

596.0

Zinc finger

C2H2-type 8

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

368_390

1.0

596.0

Zinc finger

C2H2-type 9

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

396_418

1.0

596.0

Zinc finger

C2H2-type 10

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

424_448

1.0

596.0

Zinc finger

C2H2-type 11

Hgene

ZNF440

chr19:11925265

chr19:11618863

ENST00000304060

458_480

1.0

596.0

Zinc finger

C2H2-type 12

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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 >>>388_ZNF440_11925265_ECSIT_11618863_ranked_0.pdb	ZNF440	11925265	11925265	ENST00000592312	ECSIT	chr19	11618863	-	MGQGWVGLLQALDPLSHRRLVMSTRHAHGEDRAFLHFIDVKLVVVPATPHILQVQLHRVVEVPLLRRLFHFPLLRGQQVSSEDVVIHTLV AEPQGEGALNKDRPGWIVAGQGGLLIGTLDSWCGDIHALCPARDSAQRPREPSLGPARTWQGLGKVRDLAAPMLSDLPTMWGWGGSAAPV	242

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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.

ZNF440_pLDDT.png

ECSIT_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
ZNF440
ECSIT

- 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 ZNF440-ECSIT

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 ZNF440-ECSIT

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