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:MED29-ADAM18

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: MED29-ADAM18
	FusionPDB ID: 52768
	FusionGDB2.0 ID: 52768
		Hgene	Tgene
	Gene symbol	MED29	ADAM18
	Gene ID	55588	8749
	Gene name	mediator complex subunit 29	ADAM metallopeptidase domain 18
	Synonyms	IXL\|MED2	ADAM27\|tMDCIII
	Cytomap	19q13.2	8p11.22
	Type of gene	protein-coding	protein-coding
	Description	mediator of RNA polymerase II transcription subunit 29intersex-like protein	disintegrin and metalloproteinase domain-containing protein 18a disintegrin and metalloproteinase domain 18transmembrane metalloproteinase-like, disintegrin-like, and cysteine-rich protein III
	Modification date	20200313	20200313
	UniProtAcc	Q9NX70	Q9Y3Q7
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000315588, ENST00000594368, ENST00000599213,	ENST00000523755, ENST00000520772, ENST00000541111, ENST00000265707, ENST00000379866,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	4 X 2 X 3=24	8 X 8 X 6=384
	# samples	4	9
	** MAII score	log2(4/24*10)=0.736965594166206 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0	log2(9/384*10)=-2.09310940439148 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: MED29 [Title/Abstract] AND ADAM18 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	MED29(39884277)-ADAM18(39550119), # samples:3
Anticipated loss of major functional domain due to fusion event.	MED29-ADAM18 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. MED29-ADAM18 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. MED29-ADAM18 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. MED29-ADAM18 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

Fusion gene breakpoints across MED29 (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 ADAM18 (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-85-7843-01A	MED29	chr19	39884277	-	ADAM18	chr8	39550119	+
ChimerDB4	LUSC	TCGA-85-7843-01A	MED29	chr19	39884277	+	ADAM18	chr8	39550119	+
ChimerDB4	LUSC	TCGA-85-7843	MED29	chr19	39884277	+	ADAM18	chr8	39550119	+

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)
ENST00000315588	MED29	chr19	39884277	+	ENST00000265707	ADAM18	chr8	39550119	+	994	472	49	870	273
ENST00000315588	MED29	chr19	39884277	+	ENST00000379866	ADAM18	chr8	39550119	+	995	472	49	870	273
ENST00000594368	MED29	chr19	39884277	+	ENST00000265707	ADAM18	chr8	39550119	+	912	390	30	788	252
ENST00000594368	MED29	chr19	39884277	+	ENST00000379866	ADAM18	chr8	39550119	+	913	390	30	788	252
ENST00000599213	MED29	chr19	39884277	+	ENST00000265707	ADAM18	chr8	39550119	+	909	387	27	785	252
ENST00000599213	MED29	chr19	39884277	+	ENST00000379866	ADAM18	chr8	39550119	+	910	387	27	785	252

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
ENST00000315588	ENST00000265707	MED29	chr19	39884277	+	ADAM18	chr8	39550119	+	0.004103716	0.99589634
ENST00000315588	ENST00000379866	MED29	chr19	39884277	+	ADAM18	chr8	39550119	+	0.004091855	0.99590814
ENST00000594368	ENST00000265707	MED29	chr19	39884277	+	ADAM18	chr8	39550119	+	0.001525502	0.99847454
ENST00000594368	ENST00000379866	MED29	chr19	39884277	+	ADAM18	chr8	39550119	+	0.001540026	0.99845994
ENST00000599213	ENST00000265707	MED29	chr19	39884277	+	ADAM18	chr8	39550119	+	0.001479973	0.9985201
ENST00000599213	ENST00000379866	MED29	chr19	39884277	+	ADAM18	chr8	39550119	+	0.001486362	0.99851364

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

>52768_52768_1_MED29-ADAM18_MED29_chr19_39884277_ENST00000315588_ADAM18_chr8_39550119_ENST00000265707_length(amino acids)=273AA_BP=141
MLKSNGERRSRNALPAVYARKMAASQQQASAASSAAGVSGPSSAGGPGPQQQPQPPAQLVGPAQSGLLQQQQQDFDPVQRYKMLIPQLKE
SLQTLMKVAAQNLIQNTNIDNGQKSSDGPIQRFDKCLEEFYALCDQLELCLYCVNKTCRKVHLMGYNCNATTKCKGKGICNNFGNCQCFP
GHRPPDCKFQFGSPGGSIDDGNFQKSGDFYTEKGYNTHWNNWFILSFCIFLPFFIVFTTVIFKRNEISKSCNRENAEYNRNSSVVSESDD

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

>52768_52768_2_MED29-ADAM18_MED29_chr19_39884277_ENST00000315588_ADAM18_chr8_39550119_ENST00000379866_length(amino acids)=273AA_BP=141
MLKSNGERRSRNALPAVYARKMAASQQQASAASSAAGVSGPSSAGGPGPQQQPQPPAQLVGPAQSGLLQQQQQDFDPVQRYKMLIPQLKE
SLQTLMKVAAQNLIQNTNIDNGQKSSDGPIQRFDKCLEEFYALCDQLELCLYCVNKTCRKVHLMGYNCNATTKCKGKGICNNFGNCQCFP
GHRPPDCKFQFGSPGGSIDDGNFQKSGDFYTEKGYNTHWNNWFILSFCIFLPFFIVFTTVIFKRNEISKSCNRENAEYNRNSSVVSESDD

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

>52768_52768_3_MED29-ADAM18_MED29_chr19_39884277_ENST00000594368_ADAM18_chr8_39550119_ENST00000265707_length(amino acids)=252AA_BP=120
MAASQQQASAASSAAGVSGPSSAGGPGPQQQPQPPAQLVGPAQSGLLQQQQQDFDPVQRYKMLIPQLKESLQTLMKVAAQNLIQNTNIDN
GQKSSDGPIQRFDKCLEEFYALCDQLELCLYCVNKTCRKVHLMGYNCNATTKCKGKGICNNFGNCQCFPGHRPPDCKFQFGSPGGSIDDG

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

>52768_52768_4_MED29-ADAM18_MED29_chr19_39884277_ENST00000594368_ADAM18_chr8_39550119_ENST00000379866_length(amino acids)=252AA_BP=120
MAASQQQASAASSAAGVSGPSSAGGPGPQQQPQPPAQLVGPAQSGLLQQQQQDFDPVQRYKMLIPQLKESLQTLMKVAAQNLIQNTNIDN
GQKSSDGPIQRFDKCLEEFYALCDQLELCLYCVNKTCRKVHLMGYNCNATTKCKGKGICNNFGNCQCFPGHRPPDCKFQFGSPGGSIDDG

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

>52768_52768_5_MED29-ADAM18_MED29_chr19_39884277_ENST00000599213_ADAM18_chr8_39550119_ENST00000265707_length(amino acids)=252AA_BP=120
MAASQQQASAASSAAGVSGPSSAGGPGPQQQPQPPAQLVGPAQSGLLQQQQQDFDPVQRYKMLIPQLKESLQTLMKVAAQNLIQNTNIDN
GQKSSDGPIQRFDKCLEEFYALCDQLELCLYCVNKTCRKVHLMGYNCNATTKCKGKGICNNFGNCQCFPGHRPPDCKFQFGSPGGSIDDG

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

>52768_52768_6_MED29-ADAM18_MED29_chr19_39884277_ENST00000599213_ADAM18_chr8_39550119_ENST00000379866_length(amino acids)=252AA_BP=120
MAASQQQASAASSAAGVSGPSSAGGPGPQQQPQPPAQLVGPAQSGLLQQQQQDFDPVQRYKMLIPQLKESLQTLMKVAAQNLIQNTNIDN
GQKSSDGPIQRFDKCLEEFYALCDQLELCLYCVNKTCRKVHLMGYNCNATTKCKGKGICNNFGNCQCFPGHRPPDCKFQFGSPGGSIDDG

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

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/chr19:39884277/chr8:39550119)
- 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
MED29 Q9NX70	ADAM18 Q9Y3Q7
FUNCTION: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. {ECO:0000269\|PubMed:15555573}.	FUNCTION: Sperm surface membrane protein that may be involved in spermatogenesis and fertilization. This is a non catalytic metalloprotease-like protein (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.

- 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

MED29

chr19:39884277

chr8:39550119

ENST00000599213

29_84

120.0

201.0

Compositional bias

Note=Gln-rich

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000520772

480_622

183.0

Compositional bias

Note=Cys-rich

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000265707

620_654

607.0

740.0

Domain

Note=EGF-like

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000379866

620_654

583.0

716.0

Domain

Note=EGF-like

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000520772

184_381

183.0

Domain

Peptidase M12B

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000520772

390_479

183.0

Domain

Disintegrin

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000520772

620_654

183.0

Domain

Note=EGF-like

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000265707

709_739

607.0

740.0

Topological domain

Cytoplasmic

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000379866

709_739

583.0

716.0

Topological domain

Cytoplasmic

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000520772

177_687

183.0

Topological domain

Extracellular

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000520772

709_739

183.0

Topological domain

Cytoplasmic

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000265707

688_708

607.0

740.0

Transmembrane

Helical

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000379866

688_708

583.0

716.0

Transmembrane

Helical

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000520772

688_708

183.0

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

ADAM18

chr19:39884277

chr8:39550119

ENST00000265707

480_622

607.0

740.0

Compositional bias

Note=Cys-rich

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000379866

480_622

583.0

716.0

Compositional bias

Note=Cys-rich

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000265707

184_381

607.0

740.0

Domain

Peptidase M12B

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000265707

390_479

607.0

740.0

Domain

Disintegrin

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000379866

184_381

583.0

716.0

Domain

Peptidase M12B

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000379866

390_479

583.0

716.0

Domain

Disintegrin

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000265707

177_687

607.0

740.0

Topological domain

Extracellular

Tgene

ADAM18

chr19:39884277

chr8:39550119

ENST00000379866

177_687

583.0

716.0

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 >>>469_MED29_39884277_ADAM18_39550119_ranked_0.pdb	MED29	39884277	39884277	ENST00000379866	ADAM18	chr8	39550119	+	MLKSNGERRSRNALPAVYARKMAASQQQASAASSAAGVSGPSSAGGPGPQQQPQPPAQLVGPAQSGLLQQQQQDFDPVQRYKMLIPQLKE SLQTLMKVAAQNLIQNTNIDNGQKSSDGPIQRFDKCLEEFYALCDQLELCLYCVNKTCRKVHLMGYNCNATTKCKGKGICNNFGNCQCFP GHRPPDCKFQFGSPGGSIDDGNFQKSGDFYTEKGYNTHWNNWFILSFCIFLPFFIVFTTVIFKRNEISKSCNRENAEYNRNSSVVSESDD	273

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.

MED29_pLDDT.png

ADAM18_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
MED29
ADAM18

- 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 MED29-ADAM18

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

Hgene

Tgene

Drug

Source

PMID

Top

Related Diseases to MED29-ADAM18

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