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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:SIRT6-CREB3L3 (FusionGDB2 ID:82005)

Fusion Gene Summary for SIRT6-CREB3L3

Fusion gene summary

Fusion gene information	Fusion gene name: SIRT6-CREB3L3
	Fusion gene ID: 82005
		Hgene	Tgene
	Gene symbol	SIRT6	CREB3L3
	Gene ID	51548	84699
	Gene name	sirtuin 6	cAMP responsive element binding protein 3 like 3
	Synonyms	SIR2L6	CREB-H\|CREBH\|HYST1481
	Cytomap	19p13.3	19p13.3
	Type of gene	protein-coding	protein-coding
	Description	NAD-dependent protein deacetylase sirtuin-6SIR2-like protein 6regulatory protein SIR2 homolog 6sir2-related protein type 6sirtuin type 6	cyclic AMP-responsive element-binding protein 3-like protein 3CREB/ATF family transcription factorcAMP-responsive element-binding protein, hepatic-specific
	Modification date	20200322	20200313
	UniProtAcc	.	Q68CJ9
	Ensembl transtripts involved in fusion gene	ENST00000594279, ENST00000305232, ENST00000337491, ENST00000601488, ENST00000381935,	ENST00000078445, ENST00000252587, ENST00000595923, ENST00000602147, ENST00000602257,
Fusion gene scores	* DoF score	5 X 6 X 4=120	6 X 7 X 6=252
	# samples	7	7
	** MAII score	log2(7/120*10)=-0.777607578663552 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(7/252*10)=-1.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context	PubMed: SIRT6 [Title/Abstract] AND CREB3L3 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	SIRT6(4180779)-CREB3L3(4156995), # samples:3
Anticipated loss of major functional domain due to fusion event.	SIRT6-CREB3L3 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. SIRT6-CREB3L3 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. SIRT6-CREB3L3 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF. SIRT6-CREB3L3 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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	SIRT6	GO:0010569	regulation of double-strand break repair via homologous recombination	19135889
Tgene	CREB3L3	GO:1990440	positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress	16469704

Fusion gene breakpoints across SIRT6 (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 CREB3L3 (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
ChimerDB4	LUSC	TCGA-85-8277-01A	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
ChimerDB4	LUSC	TCGA-85-8277	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
ChimerDB4	LUSC	TCGA-85-8277	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+

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Fusion Gene ORF analysis for SIRT6-CREB3L3

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
5UTR-3CDS	ENST00000594279	ENST00000078445	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
5UTR-3CDS	ENST00000594279	ENST00000078445	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
5UTR-3CDS	ENST00000594279	ENST00000252587	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
5UTR-3CDS	ENST00000594279	ENST00000252587	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
5UTR-3CDS	ENST00000594279	ENST00000595923	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
5UTR-3CDS	ENST00000594279	ENST00000595923	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
5UTR-3CDS	ENST00000594279	ENST00000602147	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
5UTR-3CDS	ENST00000594279	ENST00000602147	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
5UTR-3CDS	ENST00000594279	ENST00000602257	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
5UTR-3CDS	ENST00000594279	ENST00000602257	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000305232	ENST00000078445	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000305232	ENST00000078445	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000305232	ENST00000252587	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000305232	ENST00000252587	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000305232	ENST00000595923	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000305232	ENST00000595923	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000305232	ENST00000602147	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000305232	ENST00000602147	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000305232	ENST00000602257	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000305232	ENST00000602257	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000337491	ENST00000078445	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000337491	ENST00000078445	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000337491	ENST00000252587	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000337491	ENST00000252587	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000337491	ENST00000595923	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000337491	ENST00000595923	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000337491	ENST00000602147	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000337491	ENST00000602147	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000337491	ENST00000602257	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000337491	ENST00000602257	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000601488	ENST00000078445	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000601488	ENST00000078445	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000601488	ENST00000252587	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000601488	ENST00000252587	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000601488	ENST00000595923	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000601488	ENST00000595923	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000601488	ENST00000602147	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000601488	ENST00000602147	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
Frame-shift	ENST00000601488	ENST00000602257	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
Frame-shift	ENST00000601488	ENST00000602257	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
intron-3CDS	ENST00000381935	ENST00000078445	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
intron-3CDS	ENST00000381935	ENST00000078445	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
intron-3CDS	ENST00000381935	ENST00000252587	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
intron-3CDS	ENST00000381935	ENST00000252587	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
intron-3CDS	ENST00000381935	ENST00000595923	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
intron-3CDS	ENST00000381935	ENST00000595923	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
intron-3CDS	ENST00000381935	ENST00000602147	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
intron-3CDS	ENST00000381935	ENST00000602147	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+
intron-3CDS	ENST00000381935	ENST00000602257	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156995	+
intron-3CDS	ENST00000381935	ENST00000602257	SIRT6	chr19	4180779	-	CREB3L3	chr19	4156992	+

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 SIRT6-CREB3L3

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)
SIRT6	chr19	4180778	-	CREB3L3	chr19	4156994	+	8.83E-12	1
SIRT6	chr19	4180778	-	CREB3L3	chr19	4156994	+	8.83E-12	1
SIRT6	chr19	4180778	-	CREB3L3	chr19	4156994	+	8.83E-12	1
SIRT6	chr19	4180778	-	CREB3L3	chr19	4156994	+	8.83E-12	1

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 SIRT6-CREB3L3

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:4180779/:4156995)
- 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
.	CREB3L3 Q68CJ9
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}.	FUNCTION: Transcription factor that may act during endoplasmic reticulum stress by activating unfolded protein response target genes. Activated in response to cAMP stimulation. In vitro, binds to the cAMP response element (CRE) and box-B element. Activates transcription through box-B element. Activates transcription through CRE (By similarity). May function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression. Regulates FGF21 transcription (By similarity). {ECO:0000250, ECO:0000250\|UniProtKB:Q91XE9, ECO:0000269\|PubMed:11353085, ECO:0000269\|PubMed:15800215, ECO:0000269\|PubMed:16469704}.

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 SIRT6-CREB3L3

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 SIRT6-CREB3L3

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 SIRT6-CREB3L3

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 SIRT6-CREB3L3

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source