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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:ATL2-MAP4K4 (FusionGDB2 ID:7648)

Fusion Gene Summary for ATL2-MAP4K4

Fusion gene summary

Fusion gene information	Fusion gene name: ATL2-MAP4K4
	Fusion gene ID: 7648
		Hgene	Tgene
	Gene symbol	ATL2	MAP4K4
	Gene ID	64225	9448
	Gene name	atlastin GTPase 2	mitogen-activated protein kinase kinase kinase kinase 4
	Synonyms	ARL3IP2\|ARL6IP2\|aip-2\|atlastin2	FLH21957\|HEL-S-31\|HGK\|MEKKK4\|NIK
	Cytomap	2p22.2-p22.1	2q11.2
	Type of gene	protein-coding	protein-coding
	Description	atlastin-2ADP-ribosylation factor-like protein 6-interacting protein 2ARL-6-interacting protein 2	mitogen-activated protein kinase kinase kinase kinase 4HPK/GCK-like kinase HGKMAPK/ERK kinase kinase kinase 4MEK kinase kinase 4Ste20 group protein kinase HGKepididymis secretory protein Li 31hepatocyte progenitor kinase-like/germinal center kinase-
	Modification date	20200313	20200315
	UniProtAcc	Q8NHH9	O95819
	Ensembl transtripts involved in fusion gene	ENST00000378954, ENST00000419554, ENST00000406122, ENST00000539122, ENST00000332337, ENST00000402054, ENST00000452935, ENST00000486927, ENST00000546051,	ENST00000498066, ENST00000302217, ENST00000324219, ENST00000347699, ENST00000350198, ENST00000350878, ENST00000413150, ENST00000425019, ENST00000456652,
Fusion gene scores	* DoF score	14 X 10 X 5=700	13 X 14 X 8=1456
	# samples	16	14
	** MAII score	log2(16/700*10)=-2.12928301694497 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(14/1456*10)=-3.37851162325373 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context	PubMed: ATL2 [Title/Abstract] AND MAP4K4 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	ATL2(38604285)-MAP4K4(102483674), # samples:1
Anticipated loss of major functional domain due to fusion event.	ATL2-MAP4K4 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. ATL2-MAP4K4 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. ATL2-MAP4K4 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
Hgene	ATL2	GO:0051260	protein homooligomerization	18270207
Tgene	MAP4K4	GO:0006468	protein phosphorylation	9890973
Tgene	MAP4K4	GO:0035556	intracellular signal transduction	9890973
Tgene	MAP4K4	GO:0046328	regulation of JNK cascade	14966141

Fusion gene breakpoints across ATL2 (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 MAP4K4 (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	UCEC	TCGA-A5-A2K2-01A	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+

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Fusion Gene ORF analysis for ATL2-MAP4K4

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	ENST00000378954	ENST00000498066	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5CDS-intron	ENST00000419554	ENST00000498066	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000406122	ENST00000302217	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000406122	ENST00000324219	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000406122	ENST00000347699	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000406122	ENST00000350198	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000406122	ENST00000350878	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000406122	ENST00000413150	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000406122	ENST00000425019	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000406122	ENST00000456652	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000539122	ENST00000302217	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000539122	ENST00000324219	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000539122	ENST00000347699	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000539122	ENST00000350198	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000539122	ENST00000350878	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000539122	ENST00000413150	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000539122	ENST00000425019	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-3CDS	ENST00000539122	ENST00000456652	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-intron	ENST00000406122	ENST00000498066	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
5UTR-intron	ENST00000539122	ENST00000498066	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000378954	ENST00000302217	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000378954	ENST00000324219	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000378954	ENST00000347699	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000378954	ENST00000350198	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000378954	ENST00000350878	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000378954	ENST00000413150	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000378954	ENST00000425019	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000378954	ENST00000456652	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000419554	ENST00000302217	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000419554	ENST00000324219	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000419554	ENST00000347699	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000419554	ENST00000350198	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000419554	ENST00000350878	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000419554	ENST00000413150	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000419554	ENST00000425019	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
Frame-shift	ENST00000419554	ENST00000456652	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000332337	ENST00000302217	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000332337	ENST00000324219	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000332337	ENST00000347699	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000332337	ENST00000350198	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000332337	ENST00000350878	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000332337	ENST00000413150	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000332337	ENST00000425019	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000332337	ENST00000456652	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000402054	ENST00000302217	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000402054	ENST00000324219	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000402054	ENST00000347699	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000402054	ENST00000350198	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000402054	ENST00000350878	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000402054	ENST00000413150	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000402054	ENST00000425019	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000402054	ENST00000456652	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000452935	ENST00000302217	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000452935	ENST00000324219	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000452935	ENST00000347699	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000452935	ENST00000350198	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000452935	ENST00000350878	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000452935	ENST00000413150	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000452935	ENST00000425019	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000452935	ENST00000456652	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000486927	ENST00000302217	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000486927	ENST00000324219	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000486927	ENST00000347699	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000486927	ENST00000350198	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000486927	ENST00000350878	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000486927	ENST00000413150	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000486927	ENST00000425019	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000486927	ENST00000456652	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000546051	ENST00000302217	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000546051	ENST00000324219	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000546051	ENST00000347699	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000546051	ENST00000350198	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000546051	ENST00000350878	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000546051	ENST00000413150	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000546051	ENST00000425019	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-3CDS	ENST00000546051	ENST00000456652	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-intron	ENST00000332337	ENST00000498066	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-intron	ENST00000402054	ENST00000498066	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-intron	ENST00000452935	ENST00000498066	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-intron	ENST00000486927	ENST00000498066	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+
intron-intron	ENST00000546051	ENST00000498066	ATL2	chr2	38604285	-	MAP4K4	chr2	102483674	+

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)

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

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Fusion Genomic Features for ATL2-MAP4K4

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)
ATL2	chr2	38604284	-	MAP4K4	chr2	102483673	+	0.20088337	0.79911655
ATL2	chr2	38604284	-	MAP4K4	chr2	102483673	+	0.20088337	0.79911655

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 ATL2-MAP4K4

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:38604285/:102483674)
- 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
ATL2 Q8NHH9	MAP4K4 O95819
FUNCTION: GTPase tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis (PubMed:18270207, PubMed:19665976, PubMed:27619977). {ECO:0000269\|PubMed:18270207, ECO:0000269\|PubMed:19665976, ECO:0000269\|PubMed:27619977}.	FUNCTION: Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322. {ECO:0000269\|PubMed:21690388, ECO:0000269\|PubMed:9890973}.

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

- 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

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Fusion Gene Sequence for ATL2-MAP4K4

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.

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Fusion Gene PPI Analysis for ATL2-MAP4K4

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 ATL2-MAP4K4

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 ATL2-MAP4K4

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source