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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:MAP4K4-MBNL2

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: MAP4K4-MBNL2
	FusionPDB ID: 51408
	FusionGDB2.0 ID: 51408
		Hgene	Tgene
	Gene symbol	MAP4K4	MBNL2
	Gene ID	9448	10150
	Gene name	mitogen-activated protein kinase kinase kinase kinase 4	muscleblind like splicing regulator 2
	Synonyms	FLH21957\|HEL-S-31\|HGK\|MEKKK4\|NIK	MBLL\|MBLL39\|PRO2032
	Cytomap	2q11.2	13q32.1
	Type of gene	protein-coding	protein-coding
	Description	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-	muscleblind-like protein 2muscleblind-like 2muscleblind-like protein 1muscleblind-like protein-like 39
	Modification date	20200315	20200313
	UniProtAcc	O95819	Q5VZF2
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000302217, ENST00000324219, ENST00000347699, ENST00000350198, ENST00000413150, ENST00000425019, ENST00000456652, ENST00000350878, ENST00000498066,	ENST00000376673, ENST00000397601, ENST00000445661, ENST00000343600, ENST00000345429,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	16 X 11 X 9=1584	7 X 8 X 5=280
	# samples	16	9
	** MAII score	log2(16/1584*10)=-3.30742852519225 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(9/280*10)=-1.63742992061529 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: MAP4K4 [Title/Abstract] AND MBNL2 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	MAP4K4(102315000)-MBNL2(98043576), # samples:1
Anticipated loss of major functional domain due to fusion event.	MAP4K4-MBNL2 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. MAP4K4-MBNL2 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. MAP4K4-MBNL2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. MAP4K4-MBNL2 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. MAP4K4-MBNL2 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF. MAP4K4-MBNL2 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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	MAP4K4	GO:0006468	protein phosphorylation	9890973
Hgene	MAP4K4	GO:0035556	intracellular signal transduction	9890973
Hgene	MAP4K4	GO:0046328	regulation of JNK cascade	14966141
Tgene	MBNL2	GO:0043484	regulation of RNA splicing	15257297\|16946708

Fusion gene breakpoints across MAP4K4 (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 MBNL2 (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 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	SKCM	TCGA-DA-A1HW-06A	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+

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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)
ENST00000425019	MAP4K4	chr2	102315000	+	ENST00000343600	MBNL2	chr13	98043576	+	3258	460	481	2	160
ENST00000425019	MAP4K4	chr2	102315000	+	ENST00000345429	MBNL2	chr13	98043576	+	3259	460	374	0	125
ENST00000324219	MAP4K4	chr2	102315000	+	ENST00000343600	MBNL2	chr13	98043576	+	2995	197	1474	1698	74
ENST00000324219	MAP4K4	chr2	102315000	+	ENST00000345429	MBNL2	chr13	98043576	+	2996	197	1474	1698	74
ENST00000350198	MAP4K4	chr2	102315000	+	ENST00000343600	MBNL2	chr13	98043576	+	2995	197	1474	1698	74
ENST00000350198	MAP4K4	chr2	102315000	+	ENST00000345429	MBNL2	chr13	98043576	+	2996	197	1474	1698	74
ENST00000302217	MAP4K4	chr2	102315000	+	ENST00000343600	MBNL2	chr13	98043576	+	2995	197	1474	1698	74
ENST00000302217	MAP4K4	chr2	102315000	+	ENST00000345429	MBNL2	chr13	98043576	+	2996	197	1474	1698	74
ENST00000413150	MAP4K4	chr2	102315000	+	ENST00000343600	MBNL2	chr13	98043576	+	2976	178	1455	1679	74
ENST00000413150	MAP4K4	chr2	102315000	+	ENST00000345429	MBNL2	chr13	98043576	+	2977	178	1455	1679	74
ENST00000347699	MAP4K4	chr2	102315000	+	ENST00000343600	MBNL2	chr13	98043576	+	2921	123	1400	1624	74
ENST00000347699	MAP4K4	chr2	102315000	+	ENST00000345429	MBNL2	chr13	98043576	+	2922	123	1400	1624	74
ENST00000456652	MAP4K4	chr2	102315000	+	ENST00000343600	MBNL2	chr13	98043576	+	2921	123	1400	1624	74
ENST00000456652	MAP4K4	chr2	102315000	+	ENST00000345429	MBNL2	chr13	98043576	+	2922	123	1400	1624	74

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
ENST00000425019	ENST00000343600	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.48217636	0.51782364
ENST00000425019	ENST00000345429	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.45893586	0.54106414
ENST00000324219	ENST00000343600	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.7650391	0.23496087
ENST00000324219	ENST00000345429	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.7659475	0.23405254
ENST00000350198	ENST00000343600	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.7650391	0.23496087
ENST00000350198	ENST00000345429	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.7659475	0.23405254
ENST00000302217	ENST00000343600	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.7650391	0.23496087
ENST00000302217	ENST00000345429	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.7659475	0.23405254
ENST00000413150	ENST00000343600	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.6638201	0.33617988
ENST00000413150	ENST00000345429	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.6376417	0.36235824
ENST00000347699	ENST00000343600	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.40285352	0.5971465
ENST00000347699	ENST00000345429	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.40130973	0.5986903
ENST00000456652	ENST00000343600	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.40285352	0.5971465
ENST00000456652	ENST00000345429	MAP4K4	chr2	102315000	+	MBNL2	chr13	98043576	+	0.40130973	0.5986903

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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

>51408_51408_1_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000302217_MBNL2_chr13_98043576_ENST00000343600_length(amino acids)=74AA_BP=

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

>51408_51408_2_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000302217_MBNL2_chr13_98043576_ENST00000345429_length(amino acids)=74AA_BP=

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

>51408_51408_3_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000324219_MBNL2_chr13_98043576_ENST00000343600_length(amino acids)=74AA_BP=

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

>51408_51408_4_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000324219_MBNL2_chr13_98043576_ENST00000345429_length(amino acids)=74AA_BP=

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

>51408_51408_5_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000347699_MBNL2_chr13_98043576_ENST00000343600_length(amino acids)=74AA_BP=

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

>51408_51408_6_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000347699_MBNL2_chr13_98043576_ENST00000345429_length(amino acids)=74AA_BP=

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

>51408_51408_7_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000350198_MBNL2_chr13_98043576_ENST00000343600_length(amino acids)=74AA_BP=

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

>51408_51408_8_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000350198_MBNL2_chr13_98043576_ENST00000345429_length(amino acids)=74AA_BP=

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

>51408_51408_9_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000413150_MBNL2_chr13_98043576_ENST00000343600_length(amino acids)=74AA_BP=

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

>51408_51408_10_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000413150_MBNL2_chr13_98043576_ENST00000345429_length(amino acids)=74AA_BP=

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

>51408_51408_11_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000425019_MBNL2_chr13_98043576_ENST00000343600_length(amino acids)=160AA_BP=
MLIISELSYRLVHRCHFQPLPPAQKSQQDPAGRRGRCPPDFLQGSRSPFSLFATKKQITINVSVALCISAADQAADRAPRAAAEPARYSP

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

>51408_51408_12_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000425019_MBNL2_chr13_98043576_ENST00000345429_length(amino acids)=125AA_BP=
MSTRLFAGESFAIFPFCHQKTNNNKCLCRSVYLSRRPGRRPRSSRGSRAGPVLSSRGRGRRRRARLRSRAARGSLPAGPRGGRTERARAA

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

>51408_51408_13_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000456652_MBNL2_chr13_98043576_ENST00000343600_length(amino acids)=74AA_BP=

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

>51408_51408_14_MAP4K4-MBNL2_MAP4K4_chr2_102315000_ENST00000456652_MBNL2_chr13_98043576_ENST00000345429_length(amino acids)=74AA_BP=

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

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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/chr2:102315000/chr13:98043576)
- 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
MAP4K4 O95819	MBNL2 Q5VZF2
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}.	FUNCTION: Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. RNA-binding protein that binds to 5'ACACCC-3' core sequence, termed zipcode, within the 3'UTR of ITGA3. Binds to CUG triplet repeat expansion in myotonic dystrophy muscle cells by sequestering the target RNAs. Seems to regulate expression and localization of ITGA3 by transporting it from the nucleus to cytoplasm at adhesion plaques. May play a role in myotonic dystrophy pathophysiology (DM). {ECO:0000269\|PubMed:15257297, ECO:0000269\|PubMed:16273094, ECO:0000269\|PubMed:16946708}.

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

Hgene

MAP4K4

chr2:102315000

chr13:98043576

ENST00000347699

31_39

41.0

1240.0

Nucleotide binding

ATP

- 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

MAP4K4

chr2:102315000

chr13:98043576

ENST00000347699

25_289

41.0

1240.0

Domain

Protein kinase

Hgene

MAP4K4

chr2:102315000

chr13:98043576

ENST00000347699

926_1213

41.0

1240.0

Domain

CNH

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000343600

13_41

319.3333333333333

362.0

Zinc finger

C3H1-type 1

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000343600

176_204

319.3333333333333

362.0

Zinc finger

C3H1-type 3

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000343600

212_238

319.3333333333333

362.0

Zinc finger

C3H1-type 4

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000343600

47_73

319.3333333333333

362.0

Zinc finger

C3H1-type 2

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000345429

13_41

363.0

368.0

Zinc finger

C3H1-type 1

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000345429

176_204

363.0

368.0

Zinc finger

C3H1-type 3

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000345429

212_238

363.0

368.0

Zinc finger

C3H1-type 4

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000345429

47_73

363.0

368.0

Zinc finger

C3H1-type 2

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000376673

13_41

331.3333333333333

374.0

Zinc finger

C3H1-type 1

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000376673

176_204

331.3333333333333

374.0

Zinc finger

C3H1-type 3

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000376673

212_238

331.3333333333333

374.0

Zinc finger

C3H1-type 4

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000376673

47_73

331.3333333333333

374.0

Zinc finger

C3H1-type 2

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000397601

13_41

319.3333333333333

362.0

Zinc finger

C3H1-type 1

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000397601

176_204

319.3333333333333

362.0

Zinc finger

C3H1-type 3

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000397601

212_238

319.3333333333333

362.0

Zinc finger

C3H1-type 4

Tgene

MBNL2

chr2:102315000

chr13:98043576

ENST00000397601

47_73

319.3333333333333

362.0

Zinc finger

C3H1-type 2

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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
MAP4K4
MBNL2

- 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

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Related Drugs to MAP4K4-MBNL2

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 MAP4K4-MBNL2

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