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Fusion Protein:CIZ1-DBH

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: CIZ1-DBH
	FusionPDB ID: 16877
	FusionGDB2.0 ID: 16877
		Hgene	Tgene
	Gene symbol	CIZ1	DBH
	Gene ID	25792	1621
	Gene name	CDKN1A interacting zinc finger protein 1	dopamine beta-hydroxylase
	Synonyms	LSFR1\|NP94\|ZNF356	DBM\|ORTHYP1
	Cytomap	9q34.11	9q34.2
	Type of gene	protein-coding	protein-coding
	Description	cip1-interacting zinc finger proteinnuclear protein NP94zinc finger protein 356	dopamine beta-hydroxylasedopamine beta-hydroxylase (dopamine beta-monooxygenase)
	Modification date	20200313	20200313
	UniProtAcc	Q9ULV3 Main function of 5'-partner protein: FUNCTION: May regulate the subcellular localization of CIP/WAF1.	P09172 Main function of 5'-partner protein: FUNCTION: Conversion of dopamine to noradrenaline. {ECO:0000269\|PubMed:27148966, ECO:0000269\|PubMed:3443096, ECO:0000269\|PubMed:7961964, ECO:0000269\|PubMed:8546710}.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000476727, ENST00000325721, ENST00000357558, ENST00000372938, ENST00000372954, ENST00000538431, ENST00000541172, ENST00000277465, ENST00000372948, ENST00000393608,	ENST00000393056,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	8 X 7 X 2=112	3 X 3 X 3=27
	# samples	7	3
	** MAII score	log2(7/112*10)=-0.678071905112638 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(3/27*10)=0.15200309344505 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Fusion gene context	PubMed: CIZ1 [Title/Abstract] AND DBH [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: CIZ1 [Title/Abstract] AND DBH [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	CIZ1(130947825)-DBH(136521658), # samples:1
Anticipated loss of major functional domain due to fusion event.	CIZ1-DBH 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. CIZ1-DBH 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. CIZ1-DBH 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. CIZ1-DBH 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. CIZ1-DBH seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. CIZ1-DBH seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF. CIZ1-DBH seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF. CIZ1-DBH 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
Tgene	DBH	GO:0042420	dopamine catabolic process	3443096\|7961964

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr9:130947825/chr9:136521658)
- 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.

Retention analysis results 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, are available here.

Fusion gene breakpoints across CIZ1 (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 DBH (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 Amino Acid Sequences

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)
ENST00000393608	CIZ1	chr9	130947825	-	ENST00000393056	DBH	chr9	136521658	-	2094	791	38	1069	343
ENST00000277465	CIZ1	chr9	130947825	-	ENST00000393056	DBH	chr9	136521658	-	1894	591	3	869	288
ENST00000372948	CIZ1	chr9	130947825	-	ENST00000393056	DBH	chr9	136521658	-	2094	791	38	1069	343

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
ENST00000393608	ENST00000393056	CIZ1	chr9	130947825	-	DBH	chr9	136521658	-	0.07437167	0.92562824
ENST00000277465	ENST00000393056	CIZ1	chr9	130947825	-	DBH	chr9	136521658	-	0.06613835	0.9338616
ENST00000372948	ENST00000393056	CIZ1	chr9	130947825	-	DBH	chr9	136521658	-	0.07437167	0.92562824

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

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for CIZ1-DBH

+/-13 AA sequence from the breakpoints of the fusion protein sequences.

Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	Length(fusion protein)	BP in fusion protein	Peptide
CIZ1	chr9	130947825	DBH	chr9	136521658	591	194	QKQARTSSSTTPNRKPGGDVCQLRAL
CIZ1	chr9	130947825	DBH	chr9	136521658	791	249	QKQARTSSSTTPNRKPGGDVCQLRAL

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Potential FusionNeoAntigen Information of CIZ1-DBH in HLA I

Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

CIZ1-DBH_130947825_136521658.msa

Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)

Fusion gene	Hchr	Hbp	Tgene	Tchr	Tbp	HLA I	FusionNeoAntigen peptide	Binding score	Immunogenic score	Neoantigen start (at BP 13)	Neoantigen end (at BP 13)
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-B39:06	NRKPGGDVC	0.8249	0.7659	12	21
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A74:03	RTSSSTTPNR	0.9937	0.5569	4	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A74:11	RTSSSTTPNR	0.9937	0.5569	4	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A74:09	RTSSSTTPNR	0.9937	0.5569	4	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A11:03	RTSSSTTPNR	0.992	0.6521	4	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A31:02	RTSSSTTPNR	0.9851	0.5095	4	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A11:04	RTSSSTTPNR	0.9826	0.563	4	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A11:03	RTSSSTTPNRK	0.9982	0.6362	4	15
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A30:08	RTSSSTTPNRK	0.9967	0.7449	4	15
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A11:04	RTSSSTTPNRK	0.9966	0.5208	4	15
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A11:01	TSSSTTPNR	0.972	0.538	5	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-B73:01	NRKPGGDVC	0.4317	0.6429	12	21
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A11:01	RTSSSTTPNR	0.9926	0.6531	4	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-B39:12	NRKPGGDVCQL	0.9989	0.8054	12	23
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A11:01	RTSSSTTPNRK	0.9978	0.6216	4	15
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A11:02	TSSSTTPNR	0.972	0.538	5	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A30:01	SSSTTPNRK	0.9638	0.7619	6	15
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A74:01	RTSSSTTPNR	0.9937	0.5569	4	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A11:02	RTSSSTTPNR	0.9926	0.6531	4	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A03:02	RTSSSTTPNR	0.9793	0.5209	4	14
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A11:02	RTSSSTTPNRK	0.9978	0.6216	4	15
CIZ1-DBH	chr9	130947825	chr9	136521658	591	HLA-A30:01	RTSSSTTPNRK	0.997	0.8493	4	15

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Potential FusionNeoAntigen Information of CIZ1-DBH in HLA II

Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).

Fusion gene

Hchr

Hbp

Tgene

Tchr

Tbp

HLA II

FusionNeoAntigen peptide

Neoantigen start (at BP 13)

Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of CIZ1-DBH

3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.

File name	BPseq	Hgene	Tgene	Hchr	Hbp	Tchr	Tbp	AAlen
9065	SSSTTPNRKPGGDV	CIZ1	DBH	chr9	130947825	chr9	136521658	591

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CIZ1-DBH

Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.

HLA allele	PDB ID	File name	BPseq	Docking score	Glide score
HLA-B14:02	3BVN	9065	SSSTTPNRKPGGDV	-7.15543	-7.26883
HLA-B14:02	3BVN	9065	SSSTTPNRKPGGDV	-4.77435	-5.80965
HLA-B52:01	3W39	9065	SSSTTPNRKPGGDV	-6.80875	-6.92215
HLA-B52:01	3W39	9065	SSSTTPNRKPGGDV	-4.20386	-5.23916
HLA-A11:01	4UQ2	9065	SSSTTPNRKPGGDV	-7.5194	-8.5547
HLA-A11:01	4UQ2	9065	SSSTTPNRKPGGDV	-6.9601	-7.0735
HLA-A24:02	5HGA	9065	SSSTTPNRKPGGDV	-7.52403	-7.63743
HLA-A24:02	5HGA	9065	SSSTTPNRKPGGDV	-5.82433	-6.85963
HLA-B27:05	6PYJ	9065	SSSTTPNRKPGGDV	-3.28285	-4.31815
HLA-B44:05	3DX8	9065	SSSTTPNRKPGGDV	-5.91172	-6.94702
HLA-B44:05	3DX8	9065	SSSTTPNRKPGGDV	-4.24346	-4.35686

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Vaccine Design for the FusionNeoAntigens of CIZ1-DBH

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.

Fusion gene	Hchr	Hbp	Tchr	Tbp	Start in +/-13AA	End in +/-13AA	FusionNeoAntigen peptide sequence	FusionNeoAntigen RNA sequence
CIZ1-DBH	chr9	130947825	chr9	136521658	12	21	NRKPGGDVC	AAGCCTGGAGGAGATGTGTGTCAACTA
CIZ1-DBH	chr9	130947825	chr9	136521658	12	23	NRKPGGDVCQL	AAGCCTGGAGGAGATGTGTGTCAACTACGTGCA
CIZ1-DBH	chr9	130947825	chr9	136521658	4	14	RTSSSTTPNR	TCCTCCTCTACCACCCCCAATCGAAAGCCT
CIZ1-DBH	chr9	130947825	chr9	136521658	4	15	RTSSSTTPNRK	TCCTCCTCTACCACCCCCAATCGAAAGCCTGGA
CIZ1-DBH	chr9	130947825	chr9	136521658	5	14	TSSSTTPNR	TCCTCTACCACCCCCAATCGAAAGCCT
CIZ1-DBH	chr9	130947825	chr9	136521658	6	15	SSSTTPNRK	TCTACCACCCCCAATCGAAAGCCTGGA

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.

Fusion gene

Hchr

Hbp

Tchr

Tbp

Start in +/-13AA

End in +/-13AA

FusionNeoAntigen peptide

FusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of CIZ1-DBH

These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.

Cancer type	Fusion gene	Hchr	Hbp	Henst	Tchr	Tbp	Tenst	Sample
SARC	CIZ1-DBH	chr9	130947825	ENST00000277465	chr9	136521658	ENST00000393056	TCGA-DX-A23Z-01A

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Potential target of CAR-T therapy development for CIZ1-DBH

Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features

* Minus value of BPloci means that the break point is located before the CDS.

- In-frame and retained 'Transmembrane'.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

DBH

chr9:130947825

chr9:136521658

ENST00000393056

17_37

618.0

Transmembrane

Helical%3B Signal-anchor for type II membrane protein

Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.

Hgene

Hchr

Hbp

Henst

Tgene

Tchr

Tbp

Tenst

DeepLoc result

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Related Drugs to CIZ1-DBH

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 CIZ1-DBH

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

	Fusion Gene and Fusion Protein Summary
	Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)
	Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)
	Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)
	Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)
	Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)
	Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)
	Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)
	Potential target of CAR-T therapy development
	Information on the samples that have these potential fusion neoantigens
	Fusion Protein Targeting Drugs - (Manual Curation)
	Fusion Protein Related diseases - (Manual Curation)