UTHEALTH HOME ABOUT SBMI A-Z WEBMAIL INSIDE THE UNIVERSITY

Home

Download

Statistics

Examples

Help

Contact

level2

	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein Structure
	pLDDT scores
	Ramachandran Plot of Fusion Protein Structure
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:ATG5-EPHA7

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: ATG5-EPHA7
	FusionPDB ID: 7592
	FusionGDB2.0 ID: 7592
		Hgene	Tgene
	Gene symbol	ATG5	EPHA7
	Gene ID	9474	2045
	Gene name	autophagy related 5	EPH receptor A7
	Synonyms	APG5\|APG5-LIKE\|APG5L\|ASP\|SCAR25\|hAPG5	EHK-3\|EHK3\|EK11\|HEK11
	Cytomap	6q21	6q16.1
	Type of gene	protein-coding	protein-coding
	Description	autophagy protein 5APG5 autophagy 5-likeATG5 autophagy related 5 homologapoptosis-specific protein	ephrin type-A receptor 7EPH homology kinase 3EPH-like kinase 11Eph homology kinase-3receptor protein-tyrosine kinase HEK11tyrosine-protein kinase receptor EHK-3
	Modification date	20200313	20200313
	UniProtAcc	Q9H1Y0	Q15375
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000343245, ENST00000369076, ENST00000360666, ENST00000369070, ENST00000475645,	ENST00000369297, ENST00000369303,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	25 X 16 X 9=3600	3 X 3 X 2=18
	# samples	29	3
	** MAII score	log2(29/3600*10)=-3.6338721012021 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(3/18*10)=0.736965594166206 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Context (manual curation of fusion genes in FusionPDB)	PubMed: ATG5 [Title/Abstract] AND EPHA7 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	ATG5(106756239)-EPHA7(93982140), # samples:3
Anticipated loss of major functional domain due to fusion event.	ATG5-EPHA7 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. ATG5-EPHA7 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. ATG5-EPHA7 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. ATG5-EPHA7 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. ATG5-EPHA7 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. ATG5-EPHA7 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF. ATG5-EPHA7 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. ATG5-EPHA7 seems lost the major protein functional domain in Tgene partner, which is a kinase 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	EPHA7	GO:0048013	ephrin receptor signaling pathway	17726105
Tgene	EPHA7	GO:0050730	regulation of peptidyl-tyrosine phosphorylation	17726105
Tgene	EPHA7	GO:0070372	regulation of ERK1 and ERK2 cascade	17726105

Fusion gene breakpoints across ATG5 (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 EPHA7 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Top

Fusion Gene Sample Information

Fusion gene information from FusionGDB2.0.

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	LUSC	TCGA-98-A53B-01A	ATG5	chr6	106756239	-	EPHA7	chr6	93982140	-
ChimerDB4	LUSC	TCGA-98-A53B	ATG5	chr6	106756239	-	EPHA7	chr6	93982140	-

Top

Fusion ORF Analysis

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)

ENST00000369076

ATG5

chr6

106756239

ENST00000369303

EPHA7

chr6

93982140

5639

560

583

2232

549

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
ENST00000369076	ENST00000369303	ATG5	chr6	106756239	-	EPHA7	chr6	93982140	-	8.92E-05	0.99991083

Top

Fusion Amino Acid Sequences

For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>7592_7592_1_ATG5-EPHA7_ATG5_chr6_106756239_ENST00000369076_EPHA7_chr6_93982140_ENST00000369303_length(amino acids)=549AA_BP=
MKERVLQRSVELSWQEPEHPNGVITEYEIKYYEKDQRERTYSTVKTKSTSASINNLKPGTVYVFQIRAFTAAGYGNYSPRLDVATLEEAT
GKMFEATAVSSEQNPVIIIAVVAVAGTIILVFMVFGFIIGRRHCGYSKADQEGDEELYFHFKFPGTKTYIDPETYEDPNRAVHQFAKELD
ASCIKIERVIGAGEFGEVCSGRLKLPGKRDVAVAIKTLKVGYTEKQRRDFLCEASIMGQFDHPNVVHLEGVVTRGKPVMIVIEFMENGAL
DAFLRKHDGQFTVIQLVGMLRGIAAGMRYLADMGYVHRDLAARNILVNSNLVCKVSDFGLSRVIEDDPEAVYTTTGGKIPVRWTAPEAIQ
YRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVIKAIEEGYRLPAPMDCPAGLHQLMLDCWQKERAERPKFEQIVGILDKMIRNPNS
LKTPLGTCSRPISPLLDQNTPDFTTFCSVGEWLQAIKMERYKDNFTAAGYNSLESVARMTIEDVMSLGITLVGHQKKIMSSIQTMRAQML

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

Top

Fusion Protein Functional Features

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr6:106756239/chr6:93982140)
- 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
ATG5 Q9H1Y0	EPHA7 Q15375
FUNCTION: Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway. {ECO:0000250\|UniProtKB:Q99J83, ECO:0000269\|PubMed:12207896, ECO:0000269\|PubMed:20580051, ECO:0000269\|PubMed:22170153, ECO:0000269\|PubMed:26812546}.; FUNCTION: May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD. {ECO:0000269\|PubMed:15778222, ECO:0000269\|PubMed:7796880}.; FUNCTION: (Microbial infection) May act as a proviral factor. In association with ATG12, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection (PubMed:17709747). Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but not required once infection is established (PubMed:19666601). {ECO:0000269\|PubMed:17709747, ECO:0000269\|PubMed:19666601}.	FUNCTION: Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 AND MAPK3 which are phosphorylated upon activation of EPHA7. {ECO:0000269\|PubMed:17726105}.

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.

- 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

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

192_328

280.0

Compositional bias

Note=Cys-rich

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

32_210

280.0

Domain

Eph LBD

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

331_441

280.0

Domain

Fibronectin type-III 1

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

442_537

280.0

Domain

Fibronectin type-III 2

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

633_894

280.0

Domain

Protein kinase

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

923_987

280.0

Domain

SAM

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

442_537

441.3333333333333

999.0

Domain

Fibronectin type-III 2

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

633_894

441.3333333333333

999.0

Domain

Protein kinase

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

923_987

441.3333333333333

999.0

Domain

SAM

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

996_998

280.0

Motif

PDZ-binding

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

996_998

441.3333333333333

999.0

Motif

PDZ-binding

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

639_647

280.0

Nucleotide binding

ATP

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

639_647

441.3333333333333

999.0

Nucleotide binding

ATP

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

28_555

280.0

Topological domain

Extracellular

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

577_998

280.0

Topological domain

Cytoplasmic

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

577_998

441.3333333333333

999.0

Topological domain

Cytoplasmic

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369297

556_576

280.0

Transmembrane

Helical

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

556_576

441.3333333333333

999.0

Transmembrane

Helical

- 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

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

192_328

441.3333333333333

999.0

Compositional bias

Note=Cys-rich

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

32_210

441.3333333333333

999.0

Domain

Eph LBD

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

331_441

441.3333333333333

999.0

Domain

Fibronectin type-III 1

Tgene

EPHA7

chr6:106756239

chr6:93982140

ENST00000369303

28_555

441.3333333333333

999.0

Topological domain

Extracellular

Top

Fusion Protein Structures

PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

Fusion protein PDB link (fusion AA seq ID in FusionPDB)	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	AA seq	Len(AA seq)
PDB file >>>1174_ATG5_106756239_EPHA7_93982140_1174_ATG5_106756239_EPHA7_93982140_ranked_0.pdb	ATG5	106756239	106756239	ENST00000369303	EPHA7	chr6	93982140	-	MKERVLQRSVELSWQEPEHPNGVITEYEIKYYEKDQRERTYSTVKTKSTSASINNLKPGTVYVFQIRAFTAAGYGNYSPRLDVATLEEAT GKMFEATAVSSEQNPVIIIAVVAVAGTIILVFMVFGFIIGRRHCGYSKADQEGDEELYFHFKFPGTKTYIDPETYEDPNRAVHQFAKELD ASCIKIERVIGAGEFGEVCSGRLKLPGKRDVAVAIKTLKVGYTEKQRRDFLCEASIMGQFDHPNVVHLEGVVTRGKPVMIVIEFMENGAL DAFLRKHDGQFTVIQLVGMLRGIAAGMRYLADMGYVHRDLAARNILVNSNLVCKVSDFGLSRVIEDDPEAVYTTTGGKIPVRWTAPEAIQ YRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVIKAIEEGYRLPAPMDCPAGLHQLMLDCWQKERAERPKFEQIVGILDKMIRNPNS LKTPLGTCSRPISPLLDQNTPDFTTFCSVGEWLQAIKMERYKDNFTAAGYNSLESVARMTIEDVMSLGITLVGHQKKIMSSIQTMRAQML	549

Top

pLDDT score distribution

pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

ATG5_pLDDT.png

EPHA7_pLDDT.png

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

Top

Ramachandran Plot of Fusion Protein Structure

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

Fusion AA seq ID in FusionPDB and their Ramachandran plots

Top

Fusion Protein-Protein Interaction

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 from validated records (BIOGRID-3.4.160)

Gene

PPI interactors

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
ATG5
EPHA7

- Retained interactions in fusion protein (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost interactions due to fusion (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

Top

Related Drugs to ATG5-EPHA7

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

Top

Related Diseases to ATG5-EPHA7

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