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Fusion Protein:OSBPL9-CYP4Z1

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: OSBPL9-CYP4Z1
	FusionPDB ID: 61869
	FusionGDB2.0 ID: 61869
		Hgene	Tgene
	Gene symbol	OSBPL9	CYP4Z1
	Gene ID	114883	199974
	Gene name	oxysterol binding protein like 9	cytochrome P450 family 4 subfamily Z member 1
	Synonyms	ORP-9\|ORP9	CYP4A20
	Cytomap	1p32.3	1p33
	Type of gene	protein-coding	protein-coding
	Description	oxysterol-binding protein-related protein 9OSBP-related protein 9	cytochrome P450 4Z1CYPIVZ1cytochrome P450, family 4, subfamily Z, polypeptide 1
	Modification date	20200313	20200313
	UniProtAcc	.	Q86W10 Main function of 5'-partner protein:
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000473207, ENST00000337809, ENST00000361556, ENST00000371710, ENST00000371714, ENST00000428468, ENST00000435686, ENST00000447887, ENST00000453295, ENST00000462759, ENST00000486942, ENST00000530544, ENST00000531828,	ENST00000334194, ENST00000471598,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	15 X 11 X 8=1320	1 X 1 X 1=1
	# samples	15	1
	** MAII score	log2(15/1320*10)=-3.13750352374993 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(1/1*10)=3.32192809488736
Fusion gene context	PubMed: OSBPL9 [Title/Abstract] AND CYP4Z1 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: OSBPL9 [Title/Abstract] AND CYP4Z1 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	OSBPL9(52215867)-CYP4Z1(47533247), # samples:2
Anticipated loss of major functional domain due to fusion event.	OSBPL9-CYP4Z1 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. OSBPL9-CYP4Z1 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. OSBPL9-CYP4Z1 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. OSBPL9-CYP4Z1 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

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:52215867/chr1:47533247)
- 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 OSBPL9 (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 CYP4Z1 (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)
ENST00000371714	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2861	1043	1015	2475	486
ENST00000371710	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2597	779	751	2211	486
ENST00000337809	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2597	779	751	2211	486
ENST00000435686	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2301	483	455	1915	486
ENST00000447887	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2449	631	603	2063	486
ENST00000453295	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2312	494	466	1926	486
ENST00000428468	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2363	545	517	1977	486
ENST00000530544	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2384	566	538	1998	486
ENST00000531828	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2360	542	514	1974	486
ENST00000361556	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2230	412	384	1844	486
ENST00000462759	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2264	446	418	1878	486
ENST00000486942	OSBPL9	chr1	52215867	+	ENST00000334194	CYP4Z1	chr1	47533247	+	2038	220	192	1652	486

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
ENST00000371714	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.004697972	0.9953021
ENST00000371710	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.003565244	0.9964348
ENST00000337809	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.003565244	0.9964348
ENST00000435686	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.00330322	0.9966968
ENST00000447887	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.00284284	0.9971572
ENST00000453295	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.003159962	0.99684
ENST00000428468	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.0031629	0.996837
ENST00000530544	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.002932866	0.99706715
ENST00000531828	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.003693916	0.99630606
ENST00000361556	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.003437806	0.9965622
ENST00000462759	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.00357768	0.9964223
ENST00000486942	ENST00000334194	OSBPL9	chr1	52215867	+	CYP4Z1	chr1	47533247	+	0.003281378	0.9967186

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 OSBPL9-CYP4Z1

+/-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

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Potential FusionNeoAntigen Information of OSBPL9-CYP4Z1 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.

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)

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Potential FusionNeoAntigen Information of OSBPL9-CYP4Z1 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 OSBPL9-CYP4Z1

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of OSBPL9-CYP4Z1

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

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Vaccine Design for the FusionNeoAntigens of OSBPL9-CYP4Z1

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

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 OSBPL9-CYP4Z1

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

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Potential target of CAR-T therapy development for OSBPL9-CYP4Z1

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

CYP4Z1

chr1:52215867

chr1:47533247

ENST00000334194

10_30

506.0

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 OSBPL9-CYP4Z1

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 OSBPL9-CYP4Z1

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)