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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:MDM2-ZCCHC5 (FusionGDB2 ID:HG4193TG203430)

Fusion Gene Summary for MDM2-ZCCHC5

check button Fusion gene summary
Fusion gene informationFusion gene name: MDM2-ZCCHC5
Fusion gene ID: hg4193tg203430
HgeneTgene
Gene symbol

MDM2

ZCCHC5

Gene ID

4193

203430

Gene nameMDM2 proto-oncogeneretrotransposon Gag like 3
SynonymsACTFS|HDMX|LSKB|hdm2Mar3|Mart3|SIRH9|ZCCHC5|ZHC5
Cytomap('MDM2')('ZCCHC5')

12q15

Xq21.1

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase Mdm2MDM2 oncogene, E3 ubiquitin protein ligaseMDM2 proto-oncogene, E3 ubiquitin protein ligaseMdm2, p53 E3 ubiquitin protein ligase homologMdm2, transformed 3T3 cell double minute 2, p53 binding proteindouble minute 2, humretrotransposon Gag-like protein 3Sushi-Ichi retrotransposon homolog 9mammalian retrotransposon-derived 3zinc finger CCHC domain-containing protein 5zinc finger CCHC-type containing 5zinc finger, CCHC domain containing 5
Modification date2020032920200313
UniProtAcc

Q00987

.
Ensembl transtripts involved in fusion geneENST00000258148, ENST00000258149, 
ENST00000299252, ENST00000350057, 
ENST00000356290, ENST00000360430, 
ENST00000462284, ENST00000540827, 
ENST00000348801, ENST00000393410, 
ENST00000393412, ENST00000393413, 
ENST00000428863, ENST00000478070, 
ENST00000517852, ENST00000544125, 
ENST00000544561, ENST00000545204, 
Fusion gene scores* DoF score39 X 20 X 11=85801 X 1 X 1=1
# samples 471
** MAII scorelog2(47/8580*10)=-4.19024498582191
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(1/1*10)=3.32192809488736
Context

PubMed: MDM2 [Title/Abstract] AND ZCCHC5 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointMDM2(69230529)-ZCCHC5(77914145), # samples:1
Anticipated loss of major functional domain due to fusion event.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneMDM2

GO:0000122

negative regulation of transcription by RNA polymerase II

9271120|17310983

HgeneMDM2

GO:0006511

ubiquitin-dependent protein catabolic process

11278372|15314173|16173922|17310983

HgeneMDM2

GO:0016567

protein ubiquitination

9450543|15878855|19656744|20153724

HgeneMDM2

GO:0031648

protein destabilization

9529249|10360174|15314173

HgeneMDM2

GO:0032436

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

11278372

HgeneMDM2

GO:0034504

protein localization to nucleus

10360174

HgeneMDM2

GO:0042176

regulation of protein catabolic process

9153395

HgeneMDM2

GO:0043518

negative regulation of DNA damage response, signal transduction by p53 class mediator

9529249|10360174

HgeneMDM2

GO:0045184

establishment of protein localization

10360174

HgeneMDM2

GO:0045892

negative regulation of transcription, DNA-templated

9271120

HgeneMDM2

GO:0065003

protein-containing complex assembly

10608892|12915590

HgeneMDM2

GO:0071157

negative regulation of cell cycle arrest

9529249

HgeneMDM2

GO:0071480

cellular response to gamma radiation

16213212

HgeneMDM2

GO:0072717

cellular response to actinomycin D

15314173

HgeneMDM2

GO:1901797

negative regulation of signal transduction by p53 class mediator

16173922



check button 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4SARCTCGA-IF-A3RQ-01AMDM2chr12

69230529

+ZCCHC5chrX

77914145

-


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Fusion Gene ORF analysis for MDM2-ZCCHC5

check button 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.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5CDS-5UTRENST00000258148ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
5CDS-5UTRENST00000258149ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
5CDS-5UTRENST00000299252ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
5CDS-5UTRENST00000350057ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
5CDS-5UTRENST00000356290ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
5CDS-5UTRENST00000360430ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
5CDS-5UTRENST00000462284ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
5CDS-5UTRENST00000540827ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
intron-5UTRENST00000348801ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
intron-5UTRENST00000393410ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
intron-5UTRENST00000393412ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
intron-5UTRENST00000393413ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
intron-5UTRENST00000428863ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
intron-5UTRENST00000478070ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
intron-5UTRENST00000517852ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
intron-5UTRENST00000544125ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
intron-5UTRENST00000544561ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-
intron-5UTRENST00000545204ENST00000321110MDM2chr12

69230529

+ZCCHC5chrX

77914145

-

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

check buttonDeepORF 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.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score

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Fusion Genomic Features for MDM2-ZCCHC5


check buttonFusionAI 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.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)


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Fusion Protein Features for MDM2-ZCCHC5


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:69230529/:77914145)
- 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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
MDM2

Q00987

.
FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903). {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:30879903}.FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.

check buttonRetention 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.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for MDM2-ZCCHC5


check button 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 MDM2-ZCCHC5


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for MDM2-ZCCHC5


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
HgeneMDM2Q00987DB14548Zinc sulfate, unspecified formBinderSmall moleculeApproved|Experimental
HgeneMDM2Q00987DB01593ZincSmall moleculeApproved|Investigational
HgeneMDM2Q00987DB14487Zinc acetateSmall moleculeApproved|Investigational
HgeneMDM2Q00987DB14533Zinc chlorideBinderSmall moleculeApproved|Investigational

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Related Diseases for MDM2-ZCCHC5


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneMDM2C0007131Non-Small Cell Lung Carcinoma2CTD_human
HgeneMDM2C0006142Malignant neoplasm of breast1CTD_human
HgeneMDM2C0007621Neoplastic Cell Transformation1CTD_human
HgeneMDM2C0019693HIV Infections1CTD_human
HgeneMDM2C0021364Male infertility1CTD_human
HgeneMDM2C0025202melanoma1CTD_human
HgeneMDM2C0032927Precancerous Conditions1CTD_human
HgeneMDM2C0033578Prostatic Neoplasms1CTD_human
HgeneMDM2C0085390Li-Fraumeni Syndrome1ORPHANET
HgeneMDM2C0263859Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome1CTD_human
HgeneMDM2C0282313Condition, Preneoplastic1CTD_human
HgeneMDM2C0376358Malignant neoplasm of prostate1CTD_human
HgeneMDM2C0678222Breast Carcinoma1CTD_human
HgeneMDM2C0848676Subfertility, Male1CTD_human
HgeneMDM2C0917731Male sterility1CTD_human
HgeneMDM2C1257931Mammary Neoplasms, Human1CTD_human
HgeneMDM2C1458155Mammary Neoplasms1CTD_human
HgeneMDM2C4505456HIV Coinfection1CTD_human
HgeneMDM2C4704874Mammary Carcinoma, Human1CTD_human