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Fusion Protein:ITPR2-MRPS35

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: ITPR2-MRPS35
	FusionPDB ID: 40706
	FusionGDB2.0 ID: 40706
		Hgene	Tgene
	Gene symbol	ITPR2	MRPS35
	Gene ID	3709	60488
	Gene name	inositol 1,4,5-trisphosphate receptor type 2	mitochondrial ribosomal protein S35
	Synonyms	ANHD\|CFAP48\|INSP3R2\|IP3R2	HDCMD11P\|MDS023\|MRP-S28\|MRPS28
	Cytomap	12p11.23	12p11.22
	Type of gene	protein-coding	protein-coding
	Description	inositol 1,4,5-trisphosphate receptor type 2IP3 receptorIP3R 2cilia and flagella associated protein 48type 2 InsP3 receptor	28S ribosomal protein S35, mitochondrial28S ribosomal protein S28, mitochondrialMRP-S35S28mtS35mtmitochondrial ribosomal protein S28mitochondrial small ribosomal subunit protein mS35
	Modification date	20200313	20200313
	UniProtAcc	Q14571 Main function of 5'-partner protein: FUNCTION: Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. This release is regulated by cAMP both dependently and independently of PKA (By similarity). {ECO:0000250\|UniProtKB:Q9Z329}.	P82673 Main function of 5'-partner protein:
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000381340, ENST00000242737, ENST00000545902,	ENST00000538315, ENST00000081029,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	21 X 18 X 10=3780	15 X 8 X 7=840
	# samples	23	20
	** MAII score	log2(23/3780*10)=-4.03868046816406 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(20/840*10)=-2.0703893278914 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: ITPR2 [Title/Abstract] AND MRPS35 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: ITPR2 [Title/Abstract] AND MRPS35 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	ITPR2(26774056)-MRPS35(27888380), # samples:2
Anticipated loss of major functional domain due to fusion event.	ITPR2-MRPS35 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. ITPR2-MRPS35 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. ITPR2-MRPS35 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. ITPR2-MRPS35 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
Hgene	ITPR2	GO:0001666	response to hypoxia	19120137

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr12:26774056/chr12:27888380)
- 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 ITPR2 (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 MRPS35 (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)

ENST00000381340

ITPR2

chr12

26774056

ENST00000081029

MRPS35

chr12

27888380

5174

3879

417

4328

1303

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
ENST00000381340	ENST00000081029	ITPR2	chr12	26774056	-	MRPS35	chr12	27888380	+	0.001289505	0.9987105

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 ITPR2-MRPS35

+/-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
ITPR2	chr12	26774056	MRPS35	chr12	27888380	3879	1154	GESQVKGGEEPIEVKLSSLNLDDHAK

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Potential FusionNeoAntigen Information of ITPR2-MRPS35 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.

ITPR2-MRPS35_26774056_27888380.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)
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B18:01	IEVKLSSL	0.9964	0.7683	11	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B18:01	EEPIEVKL	0.99	0.9693	8	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B39:13	IEVKLSSL	0.962	0.8278	11	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B13:01	GEEPIEVKL	0.9966	0.9354	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B44:03	GEEPIEVKL	0.9946	0.9593	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B50:02	GEEPIEVKL	0.99	0.629	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B47:01	GEEPIEVKL	0.9891	0.6609	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B45:01	GEEPIEVKL	0.9131	0.7897	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B41:01	GEEPIEVKL	0.4468	0.9395	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B39:13	GEEPIEVKL	0.4258	0.9571	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B50:01	GEEPIEVKL	0.3945	0.6515	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B35:03	EPIEVKLSSL	0.9646	0.8266	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B08:01	EPIEVKLSSL	0.9192	0.5178	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B08:09	EPIEVKLSSL	0.8697	0.5915	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B35:02	EPIEVKLSSL	0.8631	0.8458	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B35:04	EPIEVKLSSL	0.8631	0.8458	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B40:06	GEEPIEVKL	0.9991	0.6347	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B39:08	GEEPIEVKL	0.6049	0.8467	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B42:02	EPIEVKLSSL	0.9497	0.5459	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B42:01	EPIEVKLSSL	0.9447	0.5409	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B35:12	EPIEVKLSSL	0.8631	0.8458	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B39:10	EPIEVKLSSL	0.8324	0.8385	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B39:08	GGEEPIEVKL	0.7895	0.881	6	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B39:08	KGGEEPIEVKL	0.9907	0.8853	5	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B40:04	IEVKLSSL	0.9998	0.6223	11	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B18:05	IEVKLSSL	0.9964	0.7683	11	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B18:03	IEVKLSSL	0.9934	0.7594	11	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B18:08	EEPIEVKL	0.9907	0.9343	8	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B18:05	EEPIEVKL	0.99	0.9693	8	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B18:06	EEPIEVKL	0.9878	0.9728	8	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B18:03	EEPIEVKL	0.9839	0.9672	8	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B18:11	IEVKLSSL	0.9764	0.8192	11	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B39:02	IEVKLSSL	0.975	0.8324	11	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B40:04	GEEPIEVKL	0.9993	0.7311	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B44:13	GEEPIEVKL	0.9946	0.9593	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B44:26	GEEPIEVKL	0.9946	0.9593	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B44:07	GEEPIEVKL	0.9946	0.9593	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B18:11	GEEPIEVKL	0.7522	0.951	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B39:11	GEEPIEVKL	0.5867	0.8022	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B41:03	GEEPIEVKL	0.541	0.6548	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B50:05	GEEPIEVKL	0.3945	0.6515	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B50:04	GEEPIEVKL	0.3945	0.6515	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B39:02	GEEPIEVKL	0.3742	0.9567	7	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B08:18	EPIEVKLSSL	0.9192	0.5178	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B35:09	EPIEVKLSSL	0.8631	0.8458	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B08:12	EPIEVKLSSL	0.836	0.7131	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B67:01	EPIEVKLSSL	0.8273	0.6103	9	19
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B40:04	GGEEPIEVKL	0.6288	0.7318	6	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B41:03	GGEEPIEVKL	0.4393	0.6571	6	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B40:04	KGGEEPIEVKL	0.9756	0.7179	5	16
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	HLA-B41:03	KGGEEPIEVKL	0.9651	0.5268	5	16

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Potential FusionNeoAntigen Information of ITPR2-MRPS35 in HLA II

ITPR2-MRPS35_26774056_27888380.msa

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)
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	DRB4-0101	IEVKLSSLNLDDHAK	11	26
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	DRB4-0103	IEVKLSSLNLDDHAK	11	26
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	DRB4-0104	IEVKLSSLNLDDHAK	11	26
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	DRB4-0106	IEVKLSSLNLDDHAK	11	26
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	DRB4-0107	IEVKLSSLNLDDHAK	11	26
ITPR2-MRPS35	chr12	26774056	chr12	27888380	3879	DRB4-0108	IEVKLSSLNLDDHAK	11	26

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Fusion breakpoint peptide structures of ITPR2-MRPS35

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
2801	GGEEPIEVKLSSLN	ITPR2	MRPS35	chr12	26774056	chr12	27888380	3879

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ITPR2-MRPS35

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	2801	GGEEPIEVKLSSLN	-7.9962	-8.1096
HLA-B14:02	3BVN	2801	GGEEPIEVKLSSLN	-5.70842	-6.74372
HLA-B52:01	3W39	2801	GGEEPIEVKLSSLN	-6.83737	-6.95077
HLA-B52:01	3W39	2801	GGEEPIEVKLSSLN	-4.4836	-5.5189
HLA-A11:01	4UQ2	2801	GGEEPIEVKLSSLN	-10.0067	-10.1201
HLA-A11:01	4UQ2	2801	GGEEPIEVKLSSLN	-9.03915	-10.0745
HLA-A24:02	5HGA	2801	GGEEPIEVKLSSLN	-6.56204	-6.67544
HLA-A24:02	5HGA	2801	GGEEPIEVKLSSLN	-5.42271	-6.45801
HLA-B44:05	3DX8	2801	GGEEPIEVKLSSLN	-7.85648	-8.89178
HLA-B44:05	3DX8	2801	GGEEPIEVKLSSLN	-5.3978	-5.5112
HLA-A02:01	6TDR	2801	GGEEPIEVKLSSLN	-3.37154	-4.40684

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Vaccine Design for the FusionNeoAntigens of ITPR2-MRPS35

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
ITPR2-MRPS35	chr12	26774056	chr12	27888380	11	19	IEVKLSSL	ATTGAGGTAAAGCTTTCCAGTTTG
ITPR2-MRPS35	chr12	26774056	chr12	27888380	5	16	KGGEEPIEVKL	AAAGGTGGTGAAGAGCCAATTGAGGTAAAGCTT
ITPR2-MRPS35	chr12	26774056	chr12	27888380	6	16	GGEEPIEVKL	GGTGGTGAAGAGCCAATTGAGGTAAAGCTT
ITPR2-MRPS35	chr12	26774056	chr12	27888380	7	16	GEEPIEVKL	GGTGAAGAGCCAATTGAGGTAAAGCTT
ITPR2-MRPS35	chr12	26774056	chr12	27888380	8	16	EEPIEVKL	GAAGAGCCAATTGAGGTAAAGCTT
ITPR2-MRPS35	chr12	26774056	chr12	27888380	9	19	EPIEVKLSSL	GAGCCAATTGAGGTAAAGCTTTCCAGTTTG

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
ITPR2-MRPS35	chr12	26774056	chr12	27888380	11	26	IEVKLSSLNLDDHAK	ATTGAGGTAAAGCTTTCCAGTTTGAATTTAGATGATCACGCAAAG

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Information of the samples that have these potential fusion neoantigens of ITPR2-MRPS35

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
OV	ITPR2-MRPS35	chr12	26774056	ENST00000381340	chr12	27888380	ENST00000081029	TCGA-25-1329-01A

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Potential target of CAR-T therapy development for ITPR2-MRPS35

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

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 ITPR2-MRPS35

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 ITPR2-MRPS35

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
Hgene	ITPR2	C0003132	Anoxic Encephalopathy	1	CTD_human
Hgene	ITPR2	C0018800	Cardiomegaly	1	CTD_human
Hgene	ITPR2	C0995195	Anoxia of brain	1	CTD_human
Hgene	ITPR2	C1140716	Hypoxic Brain Damage	1	CTD_human
Hgene	ITPR2	C1383860	Cardiac Hypertrophy	1	CTD_human
Hgene	ITPR2	C1527348	Brain Hypoxia	1	CTD_human
Hgene	ITPR2	C1862871	ANHIDROSIS, ISOLATED, WITH NORMAL SWEAT GLANDS	1	CTD_human;ORPHANET;UNIPROT

	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)