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:GAK-MEX3D

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: GAK-MEX3D
	FusionPDB ID: 32175
	FusionGDB2.0 ID: 32175
		Hgene	Tgene
	Gene symbol	GAK	MEX3D
	Gene ID	2580	399664
	Gene name	cyclin G associated kinase	mex-3 RNA binding family member D
	Synonyms	DNAJ26\|DNAJC26	MEX-3D\|MEX3\|OK/SW-cl.4\|RKHD1\|RNF193\|TINO
	Cytomap	4p16.3	19p13.3
	Type of gene	protein-coding	protein-coding
	Description	cyclin-G-associated kinaseauxilin-2	RNA-binding protein MEX3DRING finger and KH domain-containing protein 1RING finger protein 193bcl-2 ARE RNA binding proteinring finger (C3HC4 type) and KH domain containing 1ring finger and KH domain containing 1
	Modification date	20200313	20200313
	UniProtAcc	O14976	Q86XN8
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000314167, ENST00000511163, ENST00000509566,	ENST00000388824, ENST00000402693,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	16 X 17 X 8=2176	5 X 2 X 3=30
	# samples	18	6
	** MAII score	log2(18/2176*10)=-3.59560974492067 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(6/30*10)=1 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Context (manual curation of fusion genes in FusionPDB)	PubMed: GAK [Title/Abstract] AND MEX3D [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	GAK(875695)-MEX3D(1556922), # samples:3
Anticipated loss of major functional domain due to fusion event.	GAK-MEX3D 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. GAK-MEX3D 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. GAK-MEX3D 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. GAK-MEX3D 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. GAK-MEX3D seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. GAK-MEX3D seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. GAK-MEX3D seems lost the major protein functional domain in Hgene 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	GAK	GO:0010977	negative regulation of neuron projection development	24510904

Fusion gene breakpoints across GAK (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 MEX3D (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	PRAD	TCGA-YL-A9WL-01A	GAK	chr4	875695	-	MEX3D	chr19	1556922	-
ChimerDB4	PRAD	TCGA-YL-A9WL	GAK	chr4	875694	-	MEX3D	chr19	1556922	-
ChimerDB4	PRAD	TCGA-YL-A9WL	GAK	chr4	875695	-	MEX3D	chr19	1556922	-

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)
ENST00000314167	GAK	chr4	875695	-	ENST00000402693	MEX3D	chr19	1556922	-	4027	1772	111	1892	593
ENST00000511163	GAK	chr4	875695	-	ENST00000402693	MEX3D	chr19	1556922	-	3865	1610	3111	1564	515
ENST00000314167	GAK	chr4	875694	-	ENST00000402693	MEX3D	chr19	1556922	-	4027	1772	111	1892	593
ENST00000511163	GAK	chr4	875694	-	ENST00000402693	MEX3D	chr19	1556922	-	3865	1610	3111	1564	515

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
ENST00000314167	ENST00000402693	GAK	chr4	875695	-	MEX3D	chr19	1556922	-	0.001596804	0.99840325
ENST00000511163	ENST00000402693	GAK	chr4	875695	-	MEX3D	chr19	1556922	-	0.002492786	0.9975073
ENST00000314167	ENST00000402693	GAK	chr4	875694	-	MEX3D	chr19	1556922	-	0.001596804	0.99840325
ENST00000511163	ENST00000402693	GAK	chr4	875694	-	MEX3D	chr19	1556922	-	0.002492786	0.9975073

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

>32175_32175_1_GAK-MEX3D_GAK_chr4_875694_ENST00000314167_MEX3D_chr19_1556922_ENST00000402693_length(amino acids)=593AA_BP=553
MSLLQSALDFLAGPGSLGGASGRDQSDFVGQTVELGELRLRVRRVLAEGGFAFVYEAQDVGSGREYALKRLLSNEEEKNRAIIQEVCFMK
KLSGHPNIVQFCSAASIGKEESDTGQAEFLLLTELCKGQLVEFLKKMESRGPLSCDTVLKIFYQTCRAVQHMHRQKPPIIHRDLKVENLL
LSNQGTIKLCDFGSATTISHYPDYSWSAQRRALVEEEITRNTTPMYRTPEIIDLYSNFPIGEKQDIWALGCILYLLCFRQHPFEDGAKLR
IVNGKYSIPPHDTQYTVFHSLIRAMLQVNPEERLSIAEVVHQLQEIAAARNVNPKSPITELLEQNGGYGSATLSRGPPPPVGPAGSGYSG
GLALAEYDQPYGGFLDILRGGTERLFTNLKDTSSKVIQSVANYAKGDLDISYITSRIAVMSFPAEGVESALKNNIEDVRLFLDSKHPGHY
AVYNLSPRTYRPSRFHNRVSECGWAARRAPHLHTLYNICRNMHAWLRQDHKNVCVVHCMDGRAASAVAVCSFLCFCRLFSTAEAAVYMFS

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

>32175_32175_2_GAK-MEX3D_GAK_chr4_875694_ENST00000511163_MEX3D_chr19_1556922_ENST00000402693_length(amino acids)=515AA_BP=103
MAAAHPPAPSASAPRPLPVPLPPRVPPRLPRPPLAPADGPGHVVVRALGKDMNGLGGRRAAGGTLGLALAADADGAVHAEEVVAAGDQRS
HHLALGAHHALSRQGRGRGRRRGLAAVLGGAGVQGGAGGGRGAAGQRGGRGEGGAAWEGYGALRGSPGQRAHRVRGATARQRELQAEAAG
LGQRGRVAGGPGPTAAPGAGGGRSRGSVDRGAAAEGGQGGGALKRRPDGGRGGHGQVQRQEVEVEAEVAVVGGGRPHRGTGTLRAEGEAP
VAGAAVGAGGAWVRHGGAAAAARVEGLGGAGGAQGRVPAEAGRGRGGPSSLVGGLGPEAGGRPEQVQADVGAVGVEVAVGARVGEGASAQ
RDVRLDLLARAVHVLGHPSDREHRLLVAPGRHDVGVRPLLDALDGGALGPHHQPHHPVGHAHLDGGLSGKVGRALGGAGQTPGLAARGAD

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

>32175_32175_3_GAK-MEX3D_GAK_chr4_875695_ENST00000314167_MEX3D_chr19_1556922_ENST00000402693_length(amino acids)=593AA_BP=553
MSLLQSALDFLAGPGSLGGASGRDQSDFVGQTVELGELRLRVRRVLAEGGFAFVYEAQDVGSGREYALKRLLSNEEEKNRAIIQEVCFMK
KLSGHPNIVQFCSAASIGKEESDTGQAEFLLLTELCKGQLVEFLKKMESRGPLSCDTVLKIFYQTCRAVQHMHRQKPPIIHRDLKVENLL
LSNQGTIKLCDFGSATTISHYPDYSWSAQRRALVEEEITRNTTPMYRTPEIIDLYSNFPIGEKQDIWALGCILYLLCFRQHPFEDGAKLR
IVNGKYSIPPHDTQYTVFHSLIRAMLQVNPEERLSIAEVVHQLQEIAAARNVNPKSPITELLEQNGGYGSATLSRGPPPPVGPAGSGYSG
GLALAEYDQPYGGFLDILRGGTERLFTNLKDTSSKVIQSVANYAKGDLDISYITSRIAVMSFPAEGVESALKNNIEDVRLFLDSKHPGHY
AVYNLSPRTYRPSRFHNRVSECGWAARRAPHLHTLYNICRNMHAWLRQDHKNVCVVHCMDGRAASAVAVCSFLCFCRLFSTAEAAVYMFS

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

>32175_32175_4_GAK-MEX3D_GAK_chr4_875695_ENST00000511163_MEX3D_chr19_1556922_ENST00000402693_length(amino acids)=515AA_BP=103
MAAAHPPAPSASAPRPLPVPLPPRVPPRLPRPPLAPADGPGHVVVRALGKDMNGLGGRRAAGGTLGLALAADADGAVHAEEVVAAGDQRS
HHLALGAHHALSRQGRGRGRRRGLAAVLGGAGVQGGAGGGRGAAGQRGGRGEGGAAWEGYGALRGSPGQRAHRVRGATARQRELQAEAAG
LGQRGRVAGGPGPTAAPGAGGGRSRGSVDRGAAAEGGQGGGALKRRPDGGRGGHGQVQRQEVEVEAEVAVVGGGRPHRGTGTLRAEGEAP
VAGAAVGAGGAWVRHGGAAAAARVEGLGGAGGAQGRVPAEAGRGRGGPSSLVGGLGPEAGGRPEQVQADVGAVGVEVAVGARVGEGASAQ
RDVRLDLLARAVHVLGHPSDREHRLLVAPGRHDVGVRPLLDALDGGALGPHHQPHHPVGHAHLDGGLSGKVGRALGGAGQTPGLAARGAD

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

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/chr4:875695/chr19:1556922)
- 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
GAK O14976	MEX3D Q86XN8
FUNCTION: Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1. {ECO:0000269\|PubMed:10625686}.	FUNCTION: RNA binding protein, may be involved in post-transcriptional regulatory mechanisms. {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

GAK

chr4:875694

chr19:1556922

ENST00000314167

347_350

553.6666666666666

1312.0

Compositional bias

Note=Poly-Pro

Hgene

GAK

chr4:875695

chr19:1556922

ENST00000314167

347_350

553.6666666666666

1312.0

Compositional bias

Note=Poly-Pro

Hgene

GAK

chr4:875694

chr19:1556922

ENST00000314167

40_314

553.6666666666666

1312.0

Domain

Protein kinase

Hgene

GAK

chr4:875695

chr19:1556922

ENST00000314167

40_314

553.6666666666666

1312.0

Domain

Protein kinase

Tgene

MEX3D

chr4:875694

chr19:1556922

ENST00000388824

273_334

198.33333333333334

667.0

Domain

KH 2

Tgene

MEX3D

chr4:875694

chr19:1556922

ENST00000402693

273_334

198.33333333333334

652.0

Domain

KH 2

Tgene

MEX3D

chr4:875695

chr19:1556922

ENST00000388824

273_334

198.33333333333334

667.0

Domain

KH 2

Tgene

MEX3D

chr4:875695

chr19:1556922

ENST00000402693

273_334

198.33333333333334

652.0

Domain

KH 2

Tgene

MEX3D

chr4:875694

chr19:1556922

ENST00000388824

600_640

198.33333333333334

667.0

Zinc finger

RING-type

Tgene

MEX3D

chr4:875694

chr19:1556922

ENST00000402693

600_640

198.33333333333334

652.0

Zinc finger

RING-type

Tgene

MEX3D

chr4:875695

chr19:1556922

ENST00000388824

600_640

198.33333333333334

667.0

Zinc finger

RING-type

Tgene

MEX3D

chr4:875695

chr19:1556922

ENST00000402693

600_640

198.33333333333334

652.0

Zinc finger

RING-type

- 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

GAK

chr4:875694

chr19:1556922

ENST00000314167

1247_1311

553.6666666666666

1312.0

Domain

Hgene

GAK

chr4:875694

chr19:1556922

ENST00000314167

399_566

553.6666666666666

1312.0

Domain

Phosphatase tensin-type

Hgene

GAK

chr4:875694

chr19:1556922

ENST00000314167

572_710

553.6666666666666

1312.0

Domain

C2 tensin-type

Hgene

GAK

chr4:875695

chr19:1556922

ENST00000314167

1247_1311

553.6666666666666

1312.0

Domain

Hgene

GAK

chr4:875695

chr19:1556922

ENST00000314167

399_566

553.6666666666666

1312.0

Domain

Phosphatase tensin-type

Hgene

GAK

chr4:875695

chr19:1556922

ENST00000314167

572_710

553.6666666666666

1312.0

Domain

C2 tensin-type

Tgene

MEX3D

chr4:875694

chr19:1556922

ENST00000388824

179_240

198.33333333333334

667.0

Domain

KH 1

Tgene

MEX3D

chr4:875694

chr19:1556922

ENST00000402693

179_240

198.33333333333334

652.0

Domain

KH 1

Tgene

MEX3D

chr4:875695

chr19:1556922

ENST00000388824

179_240

198.33333333333334

667.0

Domain

KH 1

Tgene

MEX3D

chr4:875695

chr19:1556922

ENST00000402693

179_240

198.33333333333334

652.0

Domain

KH 1

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 >>>1261_GAK_875695_MEX3D_1556922_1261_GAK_875695_MEX3D_1556922_ranked_0.pdb	GAK	875694	875695	ENST00000402693	MEX3D	chr19	1556922	-	MSLLQSALDFLAGPGSLGGASGRDQSDFVGQTVELGELRLRVRRVLAEGGFAFVYEAQDVGSGREYALKRLLSNEEEKNRAIIQEVCFMK KLSGHPNIVQFCSAASIGKEESDTGQAEFLLLTELCKGQLVEFLKKMESRGPLSCDTVLKIFYQTCRAVQHMHRQKPPIIHRDLKVENLL LSNQGTIKLCDFGSATTISHYPDYSWSAQRRALVEEEITRNTTPMYRTPEIIDLYSNFPIGEKQDIWALGCILYLLCFRQHPFEDGAKLR IVNGKYSIPPHDTQYTVFHSLIRAMLQVNPEERLSIAEVVHQLQEIAAARNVNPKSPITELLEQNGGYGSATLSRGPPPPVGPAGSGYSG GLALAEYDQPYGGFLDILRGGTERLFTNLKDTSSKVIQSVANYAKGDLDISYITSRIAVMSFPAEGVESALKNNIEDVRLFLDSKHPGHY AVYNLSPRTYRPSRFHNRVSECGWAARRAPHLHTLYNICRNMHAWLRQDHKNVCVVHCMDGRAASAVAVCSFLCFCRLFSTAEAAVYMFS	593

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.

GAK_pLDDT.png

MEX3D_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
GAK
MEX3D

- 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 GAK-MEX3D

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

Hgene

Tgene

Drug

Source

PMID

Top

Related Diseases to GAK-MEX3D

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