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Fusion Protein:PGAP3-PTPN12

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: PGAP3-PTPN12
	FusionPDB ID: 64560
	FusionGDB2.0 ID: 64560
		Hgene	Tgene
	Gene symbol	PGAP3	PTPN12
	Gene ID	93210	5782
	Gene name	post-GPI attachment to proteins phospholipase 3	protein tyrosine phosphatase non-receptor type 12
	Synonyms	AGLA546\|CAB2\|PERLD1\|PP1498\|hCOS16	PTP-PEST\|PTPG1
	Cytomap	17q12	7q11.23
	Type of gene	protein-coding	protein-coding
	Description	post-GPI attachment to proteins factor 3COS16 homologgene coamplified with ERBB2 proteinper1-like domain containing 1post-GPI attachment to proteins 3	tyrosine-protein phosphatase non-receptor type 12protein-tyrosine phosphatase G1
	Modification date	20200327	20200329
	UniProtAcc	.	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000300658, ENST00000378011, ENST00000429199, ENST00000579146,	ENST00000248594, ENST00000415482, ENST00000435495,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	18 X 8 X 9=1296	14 X 11 X 7=1078
	# samples	27	14
	** MAII score	log2(27/1296*10)=-2.26303440583379 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(14/1078*10)=-2.94485844580754 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: PGAP3 [Title/Abstract] AND PTPN12 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: PGAP3 [Title/Abstract] AND PTPN12 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	PGAP3(37844087)-PTPN12(77227159), # samples:2
Anticipated loss of major functional domain due to fusion event.	PGAP3-PTPN12 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. PGAP3-PTPN12 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. PGAP3-PTPN12 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. PGAP3-PTPN12 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
Tgene	PTPN12	GO:0006470	protein dephosphorylation	27134172
Tgene	PTPN12	GO:0035335	peptidyl-tyrosine dephosphorylation	27134172

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:37844087/chr7:77227159)
- 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 PGAP3 (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 PTPN12 (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)
ENST00000579146	PGAP3	chr17	37844087	-	ENST00000248594	PTPN12	chr7	77227159	+	2866	224	296	2074	592
ENST00000579146	PGAP3	chr17	37844087	-	ENST00000415482	PTPN12	chr7	77227159	+	2075	224	296	2074	593
ENST00000579146	PGAP3	chr17	37844087	-	ENST00000435495	PTPN12	chr7	77227159	+	2415	224	296	2074	592
ENST00000300658	PGAP3	chr17	37844087	-	ENST00000248594	PTPN12	chr7	77227159	+	2916	274	346	2124	592
ENST00000300658	PGAP3	chr17	37844087	-	ENST00000415482	PTPN12	chr7	77227159	+	2125	274	346	2124	593
ENST00000300658	PGAP3	chr17	37844087	-	ENST00000435495	PTPN12	chr7	77227159	+	2465	274	346	2124	592
ENST00000378011	PGAP3	chr17	37844087	-	ENST00000248594	PTPN12	chr7	77227159	+	2866	224	296	2074	592
ENST00000378011	PGAP3	chr17	37844087	-	ENST00000415482	PTPN12	chr7	77227159	+	2075	224	296	2074	593
ENST00000378011	PGAP3	chr17	37844087	-	ENST00000435495	PTPN12	chr7	77227159	+	2415	224	296	2074	592
ENST00000429199	PGAP3	chr17	37844087	-	ENST00000248594	PTPN12	chr7	77227159	+	2866	224	296	2074	592
ENST00000429199	PGAP3	chr17	37844087	-	ENST00000415482	PTPN12	chr7	77227159	+	2075	224	296	2074	593
ENST00000429199	PGAP3	chr17	37844087	-	ENST00000435495	PTPN12	chr7	77227159	+	2415	224	296	2074	592

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
ENST00000579146	ENST00000248594	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.000710792	0.99928916
ENST00000579146	ENST00000415482	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.004602742	0.99539727
ENST00000579146	ENST00000435495	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.001501776	0.9984982
ENST00000300658	ENST00000248594	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.000713539	0.9992865
ENST00000300658	ENST00000415482	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.004551983	0.99544805
ENST00000300658	ENST00000435495	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.001491381	0.99850863
ENST00000378011	ENST00000248594	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.000710792	0.99928916
ENST00000378011	ENST00000415482	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.004602742	0.99539727
ENST00000378011	ENST00000435495	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.001501776	0.9984982
ENST00000429199	ENST00000248594	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.000710792	0.99928916
ENST00000429199	ENST00000415482	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.004602742	0.99539727
ENST00000429199	ENST00000435495	PGAP3	chr17	37844087	-	PTPN12	chr7	77227159	+	0.001501776	0.9984982

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 PGAP3-PTPN12

+/-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 PGAP3-PTPN12 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 PGAP3-PTPN12 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 PGAP3-PTPN12

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 PGAP3-PTPN12

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 PGAP3-PTPN12

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 PGAP3-PTPN12

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 PGAP3-PTPN12

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 PGAP3-PTPN12

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 PGAP3-PTPN12

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)