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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
	Related Drugs
	Related Diseases

Fusion gene:CMTM3-NCSTN (FusionGDB2 ID:17560)

Fusion Gene Summary for CMTM3-NCSTN

Fusion gene summary

Fusion gene information	Fusion gene name: CMTM3-NCSTN
	Fusion gene ID: 17560
		Hgene	Tgene
	Gene symbol	CMTM3	NCSTN
	Gene ID	123920	23385
	Gene name	CKLF like MARVEL transmembrane domain containing 3	nicastrin
	Synonyms	BNAS2\|CKLFSF3	ATAG1874
	Cytomap	16q22.1	1q23.2
	Type of gene	protein-coding	protein-coding
	Description	CKLF-like MARVEL transmembrane domain-containing protein 3chemokine-like factor superfamily member 3	nicastrinanterior pharynx-defective 2
	Modification date	20200313	20200327
	UniProtAcc	Q96MX0	Q92542
	Ensembl transtripts involved in fusion gene	ENST00000361909, ENST00000424011, ENST00000460097, ENST00000564060, ENST00000567572, ENST00000360086, ENST00000562707, ENST00000565003, ENST00000565666, ENST00000565922, ENST00000566121, ENST00000568477,	ENST00000294785, ENST00000368063, ENST00000392212, ENST00000368065, ENST00000459963, ENST00000535857,
Fusion gene scores	* DoF score	2 X 2 X 1=4	2 X 3 X 1=6
	# samples	2	3
	** MAII score	log2(2/4*10)=2.32192809488736	log2(3/6*10)=2.32192809488736
Context	PubMed: CMTM3 [Title/Abstract] AND NCSTN [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	CMTM3(66646769)-NCSTN(160328601), # samples:1
Anticipated loss of major functional domain due to fusion event.

* 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	NCSTN	GO:0006509	membrane protein ectodomain proteolysis	15274632
Tgene	NCSTN	GO:0016485	protein processing	15274632
Tgene	NCSTN	GO:0042982	amyloid precursor protein metabolic process	25043039\|26280335
Tgene	NCSTN	GO:0043085	positive regulation of catalytic activity	15274632

Fusion gene breakpoints across CMTM3 (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 NCSTN (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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
ChiTaRS5.0	N/A	CN403994	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+

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Fusion Gene ORF analysis for CMTM3-NCSTN

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.

ORF	Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
3UTR-3UTR	ENST00000361909	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000361909	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000361909	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000424011	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000424011	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000424011	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000460097	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000460097	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000460097	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000564060	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000564060	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000564060	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000567572	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000567572	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-3UTR	ENST00000567572	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000361909	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000361909	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000361909	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000424011	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000424011	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000424011	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000460097	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000460097	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000460097	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000564060	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000564060	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000564060	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000567572	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000567572	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
3UTR-intron	ENST00000567572	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000360086	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000360086	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000360086	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000562707	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000562707	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000562707	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000565003	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000565003	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000565003	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000565666	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000565666	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000565666	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000565922	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000565922	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000565922	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000566121	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000566121	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000566121	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000568477	ENST00000294785	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000568477	ENST00000368063	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-3UTR	ENST00000568477	ENST00000392212	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000360086	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000360086	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000360086	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000562707	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000562707	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000562707	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000565003	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000565003	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000565003	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000565666	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000565666	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000565666	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000565922	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000565922	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000565922	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000566121	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000566121	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000566121	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000568477	ENST00000368065	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000568477	ENST00000459963	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+
intron-intron	ENST00000568477	ENST00000535857	CMTM3	chr16	66646769	+	NCSTN	chr1	160328601	+

ORFfinder result based on the fusion transcript sequence of in-frame fusion genes.

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)

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

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Fusion Genomic Features for CMTM3-NCSTN

FusionAI 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.

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

1-p

p (fusion gene breakpoint)

Distribution 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.

Distribution 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 CMTM3-NCSTN

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:66646769/:160328601)
- 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
CMTM3 Q96MX0	NCSTN Q92542
	FUNCTION: Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10993067, PubMed:12679784, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. {ECO:0000269\|PubMed:10993067, ECO:0000269\|PubMed:12679784, ECO:0000269\|PubMed:25043039, ECO:0000269\|PubMed:26280335, ECO:0000269\|PubMed:30598546, ECO:0000269\|PubMed:30630874}.

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.

- In-frame and 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

- In-frame and 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

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Fusion Gene Sequence for CMTM3-NCSTN

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 CMTM3-NCSTN

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 (BIOGRID-3.4.160)

Hgene

Hgene's interactors

Tgene

Tgene's interactors

- Retained PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

- Retained PPIs, but lost function due to frame-shift fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs for CMTM3-NCSTN

Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)

Partner

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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Related Diseases for CMTM3-NCSTN

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source