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:MAP3K4-METTL24

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: MAP3K4-METTL24
	FusionPDB ID: 51318
	FusionGDB2.0 ID: 51318
		Hgene	Tgene
	Gene symbol	MAP3K4	METTL24
	Gene ID	4216	728464
	Gene name	mitogen-activated protein kinase kinase kinase 4	methyltransferase like 24
	Synonyms	MAPKKK4\|MEKK 4\|MEKK4\|MTK1\|PRO0412	C6orf186
	Cytomap	6q26	6q21
	Type of gene	protein-coding	protein-coding
	Description	mitogen-activated protein kinase kinase kinase 4MAP three kinase 1MAP/ERK kinase kinase 4MAPK/ERK kinase kinase 4MEK kinase 4SSK2/SSK22 MAP kinase kinase kinase, yeast, homolog ofdJ473J16.1 (mitogen-activated protein kinase kinase kinase 4)predicte	methyltransferase-like protein 24UPF0624 protein C6orf186
	Modification date	20200313	20200313
	UniProtAcc	Q9Y6R4	Q5JXM2
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000348824, ENST00000366919, ENST00000366920, ENST00000392142, ENST00000446500,	ENST00000490043, ENST00000338882,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	7 X 4 X 7=196	5 X 4 X 5=100
	# samples	7	5
	** MAII score	log2(7/196*10)=-1.48542682717024 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(5/100*10)=-1 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: MAP3K4 [Title/Abstract] AND METTL24 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	MAP3K4(161471011)-METTL24(110636684), # samples:2
Anticipated loss of major functional domain due to fusion event.	MAP3K4-METTL24 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. MAP3K4-METTL24 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. MAP3K4-METTL24 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. MAP3K4-METTL24 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
Hgene	MAP3K4	GO:0000186	activation of MAPKK activity	9305639\|9827804
Hgene	MAP3K4	GO:0043507	positive regulation of JUN kinase activity	9305639
Hgene	MAP3K4	GO:1900745	positive regulation of p38MAPK cascade	9305639

Fusion gene breakpoints across MAP3K4 (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 METTL24 (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	LGG	TCGA-E1-5304-01A	MAP3K4	chr6	161471011	+	METTL24	chr6	110636684	-
ChimerDB4	LGG	TCGA-E1-5304	MAP3K4	chr6	161471011	+	METTL24	chr6	110636684	-

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)
ENST00000366919	MAP3K4	chr6	161471011	+	ENST00000338882	METTL24	chr6	110636684	-	2614	1912	88	2595	835
ENST00000392142	MAP3K4	chr6	161471011	+	ENST00000338882	METTL24	chr6	110636684	-	2557	1855	31	2538	835
ENST00000348824	MAP3K4	chr6	161471011	+	ENST00000338882	METTL24	chr6	110636684	-	2527	1825	1	2508	835
ENST00000366920	MAP3K4	chr6	161471011	+	ENST00000338882	METTL24	chr6	110636684	-	2527	1825	1	2508	835

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
ENST00000366919	ENST00000338882	MAP3K4	chr6	161471011	+	METTL24	chr6	110636684	-	0.001815845	0.99818414
ENST00000392142	ENST00000338882	MAP3K4	chr6	161471011	+	METTL24	chr6	110636684	-	0.001794581	0.9982054
ENST00000348824	ENST00000338882	MAP3K4	chr6	161471011	+	METTL24	chr6	110636684	-	0.001682791	0.99831724
ENST00000366920	ENST00000338882	MAP3K4	chr6	161471011	+	METTL24	chr6	110636684	-	0.001682791	0.99831724

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

>51318_51318_1_MAP3K4-METTL24_MAP3K4_chr6_161471011_ENST00000348824_METTL24_chr6_110636684_ENST00000338882_length(amino acids)=835AA_BP=608
LRRGRGGGGVESLPHFGAPVPRARLQLTARRGHAGLRARMREAAAALVPPPAFAVTPAAAMEEPPPPPPPPPPPPEPETESEPECCLAAR
QEGTLGDSACKSPESDLEDFSDETNTENLYGTSPPSTPRQMKRMSTKHQRNNVGRPASRSNLKEKMNAPNQPPHKDTGKTVENVEEYSYK
QEKKIRAALRTTERDRKKNVQCSFMLDSVGGSLPKKSIPDVDLNKPYLSLGCSNAKLPVSVPMPIARPARQTSRTDCPADRLKFFETLRL
LLKLTSVSKKKDREQRGQENTSGFWLNRSNELIWLELQAWHAGRTINDQDFFLYTARQAIPDIINEILTFKVDYGSFAFVRDRAGFNGTS
VEGQCKATPGTKIVGYSTHHEHLQRQRVSFEQVKRIMELLEYIEALYPSLQALQKDYEKYAAKDFQDRVQALCLWLNITKDLNQKLRIMG
TVLGIKNLSDIGWPVFEIPSPRPSKGNEPEYEGDDTEGELKELESSTDESEEEQISDPRVPEIRQPIDNSFDIQSRDCISKKLERLESED
DSLGWGAPDWSTEAGFSRHCLTSIYRPFVDKALKQMGLRKLILRLHKLMDGSLQRARIALVKNDRPVEIACNHMNTDSLATDSSPTHKPW
SVCLDDRFNLAHQIRNKQCRLYSLGLGSDDTHFEVSMANNGCEVHRFDPSVKSAHILESQHLWYHRLSIDWRDPHPAVAAQKPHSNTRKL
GSILNEFGHHKIDVLKADLESAEWKVLENLILEDVLEQIGQLIFEIHLHWPGFEVSGSDSSVVRFWYSLLKELEQKDFRLFHSYKDLSKP

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

>51318_51318_2_MAP3K4-METTL24_MAP3K4_chr6_161471011_ENST00000366919_METTL24_chr6_110636684_ENST00000338882_length(amino acids)=835AA_BP=608
MRRGRGGGGVESLPHFGAPVPRARLQLTARRGHAGLRARMREAAAALVPPPAFAVTPAAAMEEPPPPPPPPPPPPEPETESEPECCLAAR
QEGTLGDSACKSPESDLEDFSDETNTENLYGTSPPSTPRQMKRMSTKHQRNNVGRPASRSNLKEKMNAPNQPPHKDTGKTVENVEEYSYK
QEKKIRAALRTTERDRKKNVQCSFMLDSVGGSLPKKSIPDVDLNKPYLSLGCSNAKLPVSVPMPIARPARQTSRTDCPADRLKFFETLRL
LLKLTSVSKKKDREQRGQENTSGFWLNRSNELIWLELQAWHAGRTINDQDFFLYTARQAIPDIINEILTFKVDYGSFAFVRDRAGFNGTS
VEGQCKATPGTKIVGYSTHHEHLQRQRVSFEQVKRIMELLEYIEALYPSLQALQKDYEKYAAKDFQDRVQALCLWLNITKDLNQKLRIMG
TVLGIKNLSDIGWPVFEIPSPRPSKGNEPEYEGDDTEGELKELESSTDESEEEQISDPRVPEIRQPIDNSFDIQSRDCISKKLERLESED
DSLGWGAPDWSTEAGFSRHCLTSIYRPFVDKALKQMGLRKLILRLHKLMDGSLQRARIALVKNDRPVEIACNHMNTDSLATDSSPTHKPW
SVCLDDRFNLAHQIRNKQCRLYSLGLGSDDTHFEVSMANNGCEVHRFDPSVKSAHILESQHLWYHRLSIDWRDPHPAVAAQKPHSNTRKL
GSILNEFGHHKIDVLKADLESAEWKVLENLILEDVLEQIGQLIFEIHLHWPGFEVSGSDSSVVRFWYSLLKELEQKDFRLFHSYKDLSKP

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

>51318_51318_3_MAP3K4-METTL24_MAP3K4_chr6_161471011_ENST00000366920_METTL24_chr6_110636684_ENST00000338882_length(amino acids)=835AA_BP=608
LRRGRGGGGVESLPHFGAPVPRARLQLTARRGHAGLRARMREAAAALVPPPAFAVTPAAAMEEPPPPPPPPPPPPEPETESEPECCLAAR
QEGTLGDSACKSPESDLEDFSDETNTENLYGTSPPSTPRQMKRMSTKHQRNNVGRPASRSNLKEKMNAPNQPPHKDTGKTVENVEEYSYK
QEKKIRAALRTTERDRKKNVQCSFMLDSVGGSLPKKSIPDVDLNKPYLSLGCSNAKLPVSVPMPIARPARQTSRTDCPADRLKFFETLRL
LLKLTSVSKKKDREQRGQENTSGFWLNRSNELIWLELQAWHAGRTINDQDFFLYTARQAIPDIINEILTFKVDYGSFAFVRDRAGFNGTS
VEGQCKATPGTKIVGYSTHHEHLQRQRVSFEQVKRIMELLEYIEALYPSLQALQKDYEKYAAKDFQDRVQALCLWLNITKDLNQKLRIMG
TVLGIKNLSDIGWPVFEIPSPRPSKGNEPEYEGDDTEGELKELESSTDESEEEQISDPRVPEIRQPIDNSFDIQSRDCISKKLERLESED
DSLGWGAPDWSTEAGFSRHCLTSIYRPFVDKALKQMGLRKLILRLHKLMDGSLQRARIALVKNDRPVEIACNHMNTDSLATDSSPTHKPW
SVCLDDRFNLAHQIRNKQCRLYSLGLGSDDTHFEVSMANNGCEVHRFDPSVKSAHILESQHLWYHRLSIDWRDPHPAVAAQKPHSNTRKL
GSILNEFGHHKIDVLKADLESAEWKVLENLILEDVLEQIGQLIFEIHLHWPGFEVSGSDSSVVRFWYSLLKELEQKDFRLFHSYKDLSKP

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

>51318_51318_4_MAP3K4-METTL24_MAP3K4_chr6_161471011_ENST00000392142_METTL24_chr6_110636684_ENST00000338882_length(amino acids)=835AA_BP=608
MRRGRGGGGVESLPHFGAPVPRARLQLTARRGHAGLRARMREAAAALVPPPAFAVTPAAAMEEPPPPPPPPPPPPEPETESEPECCLAAR
QEGTLGDSACKSPESDLEDFSDETNTENLYGTSPPSTPRQMKRMSTKHQRNNVGRPASRSNLKEKMNAPNQPPHKDTGKTVENVEEYSYK
QEKKIRAALRTTERDRKKNVQCSFMLDSVGGSLPKKSIPDVDLNKPYLSLGCSNAKLPVSVPMPIARPARQTSRTDCPADRLKFFETLRL
LLKLTSVSKKKDREQRGQENTSGFWLNRSNELIWLELQAWHAGRTINDQDFFLYTARQAIPDIINEILTFKVDYGSFAFVRDRAGFNGTS
VEGQCKATPGTKIVGYSTHHEHLQRQRVSFEQVKRIMELLEYIEALYPSLQALQKDYEKYAAKDFQDRVQALCLWLNITKDLNQKLRIMG
TVLGIKNLSDIGWPVFEIPSPRPSKGNEPEYEGDDTEGELKELESSTDESEEEQISDPRVPEIRQPIDNSFDIQSRDCISKKLERLESED
DSLGWGAPDWSTEAGFSRHCLTSIYRPFVDKALKQMGLRKLILRLHKLMDGSLQRARIALVKNDRPVEIACNHMNTDSLATDSSPTHKPW
SVCLDDRFNLAHQIRNKQCRLYSLGLGSDDTHFEVSMANNGCEVHRFDPSVKSAHILESQHLWYHRLSIDWRDPHPAVAAQKPHSNTRKL
GSILNEFGHHKIDVLKADLESAEWKVLENLILEDVLEQIGQLIFEIHLHWPGFEVSGSDSSVVRFWYSLLKELEQKDFRLFHSYKDLSKP

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

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/chr6:161471011/chr6:110636684)
- 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
MAP3K4 Q9Y6R4	METTL24 Q5JXM2
FUNCTION: Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. {ECO:0000269\|PubMed:12052864, ECO:0000269\|PubMed:9305639}.

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

MAP3K4

chr6:161471011

chr6:110636684

ENST00000366919

25_38

569.0

1559.0

Compositional bias

Note=Poly-Pro

Hgene

MAP3K4

chr6:161471011

chr6:110636684

ENST00000366919

4_7

569.0

1559.0

Compositional bias

Note=Poly-Ala

Hgene

MAP3K4

chr6:161471011

chr6:110636684

ENST00000392142

25_38

569.0

1609.0

Compositional bias

Note=Poly-Pro

Hgene

MAP3K4

chr6:161471011

chr6:110636684

ENST00000392142

4_7

569.0

1609.0

Compositional bias

Note=Poly-Ala

- 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

MAP3K4

chr6:161471011

chr6:110636684

ENST00000366919

1190_1202

569.0

1559.0

Compositional bias

Note=Poly-Ala

Hgene

MAP3K4

chr6:161471011

chr6:110636684

ENST00000392142

1190_1202

569.0

1609.0

Compositional bias

Note=Poly-Ala

Hgene

MAP3K4

chr6:161471011

chr6:110636684

ENST00000366919

1343_1601

569.0

1559.0

Domain

Protein kinase

Hgene

MAP3K4

chr6:161471011

chr6:110636684

ENST00000392142

1343_1601

569.0

1609.0

Domain

Protein kinase

Hgene

MAP3K4

chr6:161471011

chr6:110636684

ENST00000366919

1349_1357

569.0

1559.0

Nucleotide binding

ATP

Hgene

MAP3K4

chr6:161471011

chr6:110636684

ENST00000392142

1349_1357

569.0

1609.0

Nucleotide binding

ATP

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 >>>1622_MAP3K4_161471011_METTL24_110636684_ranked_0.pdb	MAP3K4	161471011	161471011	ENST00000338882	METTL24	chr6	110636684	-	MRRGRGGGGVESLPHFGAPVPRARLQLTARRGHAGLRARMREAAAALVPPPAFAVTPAAAMEEPPPPPPPPPPPPEPETESEPECCLAAR QEGTLGDSACKSPESDLEDFSDETNTENLYGTSPPSTPRQMKRMSTKHQRNNVGRPASRSNLKEKMNAPNQPPHKDTGKTVENVEEYSYK QEKKIRAALRTTERDRKKNVQCSFMLDSVGGSLPKKSIPDVDLNKPYLSLGCSNAKLPVSVPMPIARPARQTSRTDCPADRLKFFETLRL LLKLTSVSKKKDREQRGQENTSGFWLNRSNELIWLELQAWHAGRTINDQDFFLYTARQAIPDIINEILTFKVDYGSFAFVRDRAGFNGTS VEGQCKATPGTKIVGYSTHHEHLQRQRVSFEQVKRIMELLEYIEALYPSLQALQKDYEKYAAKDFQDRVQALCLWLNITKDLNQKLRIMG TVLGIKNLSDIGWPVFEIPSPRPSKGNEPEYEGDDTEGELKELESSTDESEEEQISDPRVPEIRQPIDNSFDIQSRDCISKKLERLESED DSLGWGAPDWSTEAGFSRHCLTSIYRPFVDKALKQMGLRKLILRLHKLMDGSLQRARIALVKNDRPVEIACNHMNTDSLATDSSPTHKPW SVCLDDRFNLAHQIRNKQCRLYSLGLGSDDTHFEVSMANNGCEVHRFDPSVKSAHILESQHLWYHRLSIDWRDPHPAVAAQKPHSNTRKL GSILNEFGHHKIDVLKADLESAEWKVLENLILEDVLEQIGQLIFEIHLHWPGFEVSGSDSSVVRFWYSLLKELEQKDFRLFHSYKDLSKP	835

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.

MAP3K4_pLDDT.png

METTL24_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
MAP3K4
METTL24

- 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 MAP3K4-METTL24

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

Hgene

Tgene

Drug

Source

PMID

Top

Related Diseases to MAP3K4-METTL24

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