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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
	Related Drugs
	Related Diseases

Fusion gene:SHC3-PTPLAD2 (FusionGDB2 ID:81655)

Fusion Gene Summary for SHC3-PTPLAD2

Fusion gene summary

Fusion gene information	Fusion gene name: SHC3-PTPLAD2
	Fusion gene ID: 81655
		Hgene	Tgene
	Gene symbol	SHC3	PTPLAD2
	Gene ID	53358	401494
	Gene name	SHC adaptor protein 3	3-hydroxyacyl-CoA dehydratase 4
	Synonyms	N-Shc\|NSHC\|RAI\|SHCC	PTPLAD2
	Cytomap	9q22.1	9p21.3
	Type of gene	protein-coding	protein-coding
	Description	SHC-transforming protein 3SH2 domain protein C3SHC (Src homology 2 domain containing) transforming protein 3SHC-transforming protein CShc3 p51neuronal Shcprotein Raisrc homology 2 domain-containing transforming protein C3	very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 4protein tyrosine phosphatase-like A domain containing 2protein tyrosine phosphatase-like protein PTPLAD2protein-tyrosine phosphatase-like A domain-containing protein 2very-long-chain (3R)-3-hydroxyac
	Modification date	20200313	20200313
	UniProtAcc	.	.
	Ensembl transtripts involved in fusion gene	ENST00000375835, ENST00000375830, ENST00000375831,	ENST00000488436, ENST00000495827, ENST00000513293,
Fusion gene scores	* DoF score	4 X 4 X 3=48	4 X 3 X 2=24
	# samples	4	5
	** MAII score	log2(4/48*10)=-0.263034405833794 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(5/24*10)=1.05889368905357 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Context	PubMed: SHC3 [Title/Abstract] AND PTPLAD2 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	SHC3(91792902)-PTPLAD2(21029397), # samples:1
Anticipated loss of major functional domain due to fusion event.	SHC3-PTPLAD2 seems lost the major protein functional domain in Hgene partner, which is a essential gene 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	PTPLAD2	GO:0030497	fatty acid elongation	18554506
Tgene	PTPLAD2	GO:0042761	very long-chain fatty acid biosynthetic process	18554506

Fusion gene breakpoints across SHC3 (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 PTPLAD2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.

Source	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	LGG	TCGA-E1-A7YI-01A	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-

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Fusion Gene ORF analysis for SHC3-PTPLAD2

Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.

ORF	Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
5CDS-intron	ENST00000375835	ENST00000488436	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-
5UTR-3CDS	ENST00000375830	ENST00000495827	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-
5UTR-3CDS	ENST00000375830	ENST00000513293	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-
5UTR-intron	ENST00000375830	ENST00000488436	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-
Frame-shift	ENST00000375835	ENST00000495827	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-
In-frame	ENST00000375835	ENST00000513293	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-
intron-3CDS	ENST00000375831	ENST00000495827	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-
intron-3CDS	ENST00000375831	ENST00000513293	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-
intron-intron	ENST00000375831	ENST00000488436	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-

ORFfinder result based on the fusion transcript sequence of in-frame fusion genes.

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)

ENST00000375835

SHC3

chr9

91792902

ENST00000513293

PTPLAD2

chr9

21029397

2855

781

157

786

209

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
ENST00000375835	ENST00000513293	SHC3	chr9	91792902	-	PTPLAD2	chr9	21029397	-	0.024069343	0.97593063

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Fusion Genomic Features for SHC3-PTPLAD2

FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

1-p

p (fusion gene breakpoint)

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for SHC3-PTPLAD2

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr9:91792902/chr9:21029397)
- 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.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
.	.
FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.	FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page

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

- In-frame and retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

228_231

233.0

Compositional bias

Note=Poly-Lys

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

228_231

635.3333333333334

Compositional bias

Note=Poly-Lys

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

134_135

233.0

Topological domain

Lumenal

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

157_157

233.0

Topological domain

Cytoplasmic

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

179_189

233.0

Topological domain

Lumenal

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

211_232

233.0

Topological domain

Cytoplasmic

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

41_56

233.0

Topological domain

Lumenal

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

78_112

233.0

Topological domain

Cytoplasmic

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

134_135

635.3333333333334

Topological domain

Lumenal

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

157_157

635.3333333333334

Topological domain

Cytoplasmic

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

179_189

635.3333333333334

Topological domain

Lumenal

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

211_232

635.3333333333334

Topological domain

Cytoplasmic

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

41_56

635.3333333333334

Topological domain

Lumenal

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

78_112

635.3333333333334

Topological domain

Cytoplasmic

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

113_133

233.0

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

136_156

233.0

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

158_178

233.0

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

190_210

233.0

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

20_40

233.0

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

57_77

233.0

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

113_133

635.3333333333334

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

136_156

635.3333333333334

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

158_178

635.3333333333334

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

190_210

635.3333333333334

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

20_40

635.3333333333334

Transmembrane

Helical

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

57_77

635.3333333333334

Transmembrane

Helical

- In-frame and not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

SHC3

chr9:91792902

chr9:21029397

ENST00000375835

149_334

158

595.0

Domain

PID

Hgene

SHC3

chr9:91792902

chr9:21029397

ENST00000375835

499_590

158

595.0

Domain

SH2

Hgene

SHC3

chr9:91792902

chr9:21029397

ENST00000375835

335_498

158

595.0

Region

Note=CH1

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000495827

1_19

233.0

Topological domain

Cytoplasmic

Tgene

PTPLAD2

chr9:91792902

chr9:21029397

ENST00000513293

1_19

635.3333333333334

Topological domain

Cytoplasmic

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Fusion Gene Sequence for SHC3-PTPLAD2

For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>81655_81655_1_SHC3-PTPLAD2_SHC3_chr9_91792902_ENST00000375835_PTPLAD2_chr9_21029397_ENST00000513293_length(transcript)=2855nt_BP=781nt
TGCTTTTGCTGTGAGCAGCCCCAAGCAGCTGGGCGCTCCATCAGAGGCAACTATGACTTTTGCAAAGCAAACGTGCAACCCCAAGCAGCG
GTCTCCCGGGCCGGGGCTGCGCGGCCGCCGCTGTGCTGGCTTTTAACGGTGGGAGGGCACCATCCTCTTGCTCTGCTCTCGTTCTCCAGA
AGGCTGTCCCGGGGCCCCCACTCTCCGTCCCGCTCCGGGGACAGTGGCTCGCCTGCTATGCGCGGCAGCCCGCGCCGGGGCCGGCACCAG
CAGCGCCCGGGCGGATGCAGCGAGCCCACGGAGGGGCATGCTTCCACGCACCAAGTATAACCGCTTCAGGAATGACTCGGTGACATCGGT
CGATGACCTTCTCCACAGCCTGTCGGTGAGCGGCGGCGGAGGCAAGGTTTCGGCGGCGCGCGCGACCCCGGCGGCGGCTCCCTACTTGGT
GTCCGGCGAGGCGCTGCGCAAGGCGCCCGACGATGGGCCCGGCAGCCTGGGCCACCTGCTCCACAAGGTGTCCCACCTGAAACTCTCCAG
CTCGGGCCTCCGCGGCCTGTCGTCGGCCGCCCGGGAGCGGGCGGGCGCGCGGCTCTCGGGCAGCTGCAGCGCGCCCAGCCTGGCCGCCCC
GGACGGCAGTGCGCCCTCGGCGCCCCGCGCCCCGGCCATGAGCGCCGCCAGGAAGGGCCGGCCCGGCGACGAGCCGCTGCCCAGGCCCCC
TCGGGGGGCGCCGCACGCCAGCGACCAGGTGCTGGGGCCCGGAGTCACCTACGTGGTCAAGGTATAGGAAGAATGCGTATCTTTTCATCT
ATTACTTAATCCAGTTCTGTGGCCACTCTTGGATATTTACAAATATGACAGTCAGATTCTTTTCATTTGGAAAAGATTCAATGGTTGACA
CTTTTTATGCTATTGGACTTGTGATGCGACTTTGCCAATCCGTATCTCTCCTGGAACTGCTGCACATATATGTTGGCATTGAGTCAAACC
ATCTTCTCCCAAGGTTTTTGCAGCTCACAGAAAGAATAATCATCCTTTTTGTGGTGATCACCAGTCAAGAGGAAGTCCAAGAGAAATATG
TGGTGTGTGTTTTATTCGTCTTTTGGAATCTATTGGATATGGTTAGGTACACTTATAGCATGTTATCAGTCATAGGAATATCCTATGCTG
TCTTGACATGGCTCAGTCAAACACTATGGATGCCAATTTATCCTTTGTGTGTTCTTGCTGAAGCATTTGCCATCTATCAATCGCTGCCTT
ATTTTGAATCATTTGGCACTTATTCCACCAAGCTGCCCTTTGACTTATCCATCTATTTCCCATATGTGCTGAAAATATATCTCATGATGC
TCTTTATAGGTATGTATTTTACCTACAGTCATCTATACTCAGAAAGAAGAGACATCCTCGGAATCTTTCCCATTAAAAAAAAGAAGATGT
GAAGTACAGCATTCCAGTGTGACACGAGAAAAGACAGGCTGTGGATTCAGTGCAGTAAATAAAACACAGGAAGTATTCTGGTGGAAAAAT
ACCTTGTATTTGATAAAAATCCATTACATGAAATAACTGCACATACCCCCAAAACTCTAGACATAACAGGCTATGTTTTTCACACATTGT
ATTTTTAAGACATATATATTCTCCATACCCTGCTTCACCAAAATTCCTGCTTCATTTGGATTTTATACAAGTTATACTTACATTGTATGA
AGTCTGATTATTTTCCTGTAAGTTTAATGAGAAATAGGAGATTAGCTGCAATAGATTCAATTAAATTAAGAAACCAAACTTGATAACCTA
AATTACATGTATTCTTTTTCACTTCCAAGTTCCCAAATAGATCTGTAGGAGAAGAGGGATGGAAAATATATTCCACAGTTGCCTAGAATA
ACATATTTCATAGACAGATGTCTGTCTTCAGATCTAATAATACTCACCCTAAACATTAGATATGTTTAGAAAATTAAATATCTTTCCAAG
CCCTATGTCTTAGCTCAGGTTGCTATAATAGAACACCATAAACCGAATGGCTTAAACAACAGCAAACGCTTCTCACAGTTCTGGAGGCTG
GGAATTCCGCTCAGGATCAAGGCATCAGCTAATGCAGTTTCTGGACCCAGTGAGGCAGAGGTATTGCCCCCAGGACTATGTTGGAGGAGG
ATGACCCCCATATCACCAGGCGGAAGCTGTCAGGCCTGTTGAAACCAAGGCAATGACTGCCCCTTTTGAAACTGAGAAGCAGGGAGAAGA
TAATATCTTCAAGCTTTCACAAAGAAAATCTCCACATTGAACTCAAGCCAAATAAAGAAAATCCAAGTTCCTGTTTCAGTCTCAACTGGC
CCGGGTACTAAAGCAATGCACTCCTCTCTTAGGAGGCATGTGTCAAGCTGTCAGTGATGTGGCCATCTTTTCATGACCCTTAACTCTCTG
CATCATGTCTCAGCAATACCAGGCATGAATTCTGAAAAACTTCTTCCACTTATATGGTTTTCCTCATCCAGCTGAGAATGCTGCTGGTTA
CTGCAAAACTGTTCACCAACCATATGCTCTGGTCCATACAGCTTTCTTCTTAAACTCTGGGAGAACTCTCAAGGACAGCAGGGTGGCTAA
GGGGACAAAATATAGGTATGGCTGCATTTGAAAAGGTCATTTTGATCAAAAAGGTGTCAGAACAGAATTTGTCTTTTTCTCACTTGGCTA
ATGTTCAAGACTAGGGAGTTCCATCGATATTTTGGCAGGATTTTAATGGCAGAAAACCATTTATAAATGTTGGGGGGAAAGTTGTTTTTT

>81655_81655_1_SHC3-PTPLAD2_SHC3_chr9_91792902_ENST00000375835_PTPLAD2_chr9_21029397_ENST00000513293_length(amino acids)=209AA_BP=
MLCSRSPEGCPGAPTLRPAPGTVARLLCAAARAGAGTSSARADAASPRRGMLPRTKYNRFRNDSVTSVDDLLHSLSVSGGGGKVSAARAT
PAAAPYLVSGEALRKAPDDGPGSLGHLLHKVSHLKLSSSGLRGLSSAARERAGARLSGSCSAPSLAAPDGSAPSAPRAPAMSAARKGRPG

--------------------------------------------------------------

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Fusion Gene PPI Analysis for SHC3-PTPLAD2

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)

Hgene

Hgene's interactors

Tgene

Tgene's interactors

- Retained PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

- Retained PPIs, but lost function due to frame-shift fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs for SHC3-PTPLAD2

Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)

Partner

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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Related Diseases for SHC3-PTPLAD2

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source