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Fusion Protein:TRAPPC10-GRIK1

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: TRAPPC10-GRIK1
	FusionPDB ID: 93766
	FusionGDB2.0 ID: 93766
		Hgene	Tgene
	Gene symbol	TRAPPC10	GRIK1
	Gene ID	7109	2897
	Gene name	trafficking protein particle complex 10	glutamate ionotropic receptor kainate type subunit 1
	Synonyms	EHOC-1\|EHOC1\|GT334\|TMEM1\|TRS130\|TRS30	EAA3\|EEA3\|GLR5\|GLUR5\|GluK1\|gluR-5
	Cytomap	21q22.3	21q21.3
	Type of gene	protein-coding	protein-coding
	Description	trafficking protein particle complex subunit 10TRAPP 130 kDa subunitTRAPP subunit TMEM1epilepsy holoprosencephaly candidate-1 proteintrafficking protein particle complex subunit 130trafficking protein particle complex subunit TMEM1transmembrane prot	glutamate receptor ionotropic, kainate 1excitatory amino acid receptor 3glutamate receptor 5
	Modification date	20200313	20200320
	UniProtAcc	P48553 Main function of 5'-partner protein: FUNCTION: Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether. {ECO:0000269\|PubMed:11805826, ECO:0000269\|PubMed:31467083}.	P39086 Main function of 5'-partner protein: FUNCTION: Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000291574, ENST00000380221, ENST00000483973,	ENST00000472429, ENST00000309434, ENST00000327783, ENST00000389124, ENST00000389125, ENST00000399907, ENST00000399909, ENST00000399913, ENST00000399914, ENST00000535441,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	13 X 10 X 11=1430	12 X 9 X 6=648
	# samples	18	12
	** MAII score	log2(18/1430*10)=-2.98994633533608 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(12/648*10)=-2.43295940727611 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: TRAPPC10 [Title/Abstract] AND GRIK1 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: TRAPPC10 [Title/Abstract] AND GRIK1 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	TRAPPC10(45432441)-GRIK1(31066382), # samples:3
Anticipated loss of major functional domain due to fusion event.	TRAPPC10-GRIK1 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. TRAPPC10-GRIK1 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/chr21:45432441/chr21:31066382)
- 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 TRAPPC10 (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 GRIK1 (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)
ENST00000291574	TRAPPC10	chr21	45432441	+	ENST00000327783	GRIK1	chr21	31066382	-	3271	242	334	2973	879
ENST00000291574	TRAPPC10	chr21	45432441	+	ENST00000389125	GRIK1	chr21	31066382	-	3139	242	334	2841	835
ENST00000291574	TRAPPC10	chr21	45432441	+	ENST00000399913	GRIK1	chr21	31066382	-	3184	242	334	2886	850
ENST00000291574	TRAPPC10	chr21	45432441	+	ENST00000399914	GRIK1	chr21	31066382	-	3226	242	334	2928	864
ENST00000291574	TRAPPC10	chr21	45432441	+	ENST00000535441	GRIK1	chr21	31066382	-	2893	242	334	2892	853
ENST00000291574	TRAPPC10	chr21	45432441	+	ENST00000389124	GRIK1	chr21	31066382	-	2804	242	334	2739	801
ENST00000291574	TRAPPC10	chr21	45432441	+	ENST00000399907	GRIK1	chr21	31066382	-	3184	242	334	2880	848
ENST00000291574	TRAPPC10	chr21	45432441	+	ENST00000399909	GRIK1	chr21	31066382	-	3139	242	334	2835	833
ENST00000291574	TRAPPC10	chr21	45432441	+	ENST00000309434	GRIK1	chr21	31066382	-	2887	242	334	2886	851
ENST00000380221	TRAPPC10	chr21	45432441	+	ENST00000327783	GRIK1	chr21	31066382	-	3271	242	334	2973	879
ENST00000380221	TRAPPC10	chr21	45432441	+	ENST00000389125	GRIK1	chr21	31066382	-	3139	242	334	2841	835
ENST00000380221	TRAPPC10	chr21	45432441	+	ENST00000399913	GRIK1	chr21	31066382	-	3184	242	334	2886	850
ENST00000380221	TRAPPC10	chr21	45432441	+	ENST00000399914	GRIK1	chr21	31066382	-	3226	242	334	2928	864
ENST00000380221	TRAPPC10	chr21	45432441	+	ENST00000535441	GRIK1	chr21	31066382	-	2893	242	334	2892	853
ENST00000380221	TRAPPC10	chr21	45432441	+	ENST00000389124	GRIK1	chr21	31066382	-	2804	242	334	2739	801
ENST00000380221	TRAPPC10	chr21	45432441	+	ENST00000399907	GRIK1	chr21	31066382	-	3184	242	334	2880	848
ENST00000380221	TRAPPC10	chr21	45432441	+	ENST00000399909	GRIK1	chr21	31066382	-	3139	242	334	2835	833
ENST00000380221	TRAPPC10	chr21	45432441	+	ENST00000309434	GRIK1	chr21	31066382	-	2887	242	334	2886	851

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
ENST00000291574	ENST00000327783	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000516156	0.9994838
ENST00000291574	ENST00000389125	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000714031	0.999286
ENST00000291574	ENST00000399913	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000623465	0.9993766
ENST00000291574	ENST00000399914	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000575089	0.99942493
ENST00000291574	ENST00000535441	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.001387969	0.99861205
ENST00000291574	ENST00000389124	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.00138366	0.99861634
ENST00000291574	ENST00000399907	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000688398	0.99931157
ENST00000291574	ENST00000399909	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000838097	0.99916196
ENST00000291574	ENST00000309434	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.001181272	0.9988187
ENST00000380221	ENST00000327783	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000516156	0.9994838
ENST00000380221	ENST00000389125	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000714031	0.999286
ENST00000380221	ENST00000399913	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000623465	0.9993766
ENST00000380221	ENST00000399914	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000575089	0.99942493
ENST00000380221	ENST00000535441	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.001387969	0.99861205
ENST00000380221	ENST00000389124	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.00138366	0.99861634
ENST00000380221	ENST00000399907	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000688398	0.99931157
ENST00000380221	ENST00000399909	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.000838097	0.99916196
ENST00000380221	ENST00000309434	TRAPPC10	chr21	45432441	+	GRIK1	chr21	31066382	-	0.001181272	0.9988187

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 TRAPPC10-GRIK1

+/-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 TRAPPC10-GRIK1 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 TRAPPC10-GRIK1 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 TRAPPC10-GRIK1

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 TRAPPC10-GRIK1

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 TRAPPC10-GRIK1

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 TRAPPC10-GRIK1

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 TRAPPC10-GRIK1

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

GRIK1

chr21:45432441

chr21:31066382

ENST00000389125

577_597

906.0

Transmembrane

Helical

Tgene

GRIK1

chr21:45432441

chr21:31066382

ENST00000389125

654_674

906.0

Transmembrane

Helical

Tgene

GRIK1

chr21:45432441

chr21:31066382

ENST00000389125

835_855

906.0

Transmembrane

Helical

Tgene

GRIK1

chr21:45432441

chr21:31066382

ENST00000399907

577_597

919.0

Transmembrane

Helical

Tgene

GRIK1

chr21:45432441

chr21:31066382

ENST00000399907

654_674

919.0

Transmembrane

Helical

Tgene

GRIK1

chr21:45432441

chr21:31066382

ENST00000399907

835_855

919.0

Transmembrane

Helical

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 TRAPPC10-GRIK1

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 TRAPPC10-GRIK1

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	TRAPPC10	C0037274	Dermatologic disorders	1	CTD_human
Hgene	TRAPPC10	C0274861	Arsenic Poisoning, Inorganic	1	CTD_human
Hgene	TRAPPC10	C0274862	Nervous System, Organic Arsenic Poisoning	1	CTD_human
Hgene	TRAPPC10	C0311375	Arsenic Poisoning	1	CTD_human
Hgene	TRAPPC10	C0751851	Arsenic Encephalopathy	1	CTD_human
Hgene	TRAPPC10	C0751852	Arsenic Induced Polyneuropathy	1	CTD_human

	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)