ExonSkipAD: functional annotation of exon skipping event in human

Gene summary for MDM2

Gene summary

Gene information	Gene symbol	MDM2
	Gene ID	4193
	Gene name	MDM2 proto-oncogene
	Synonyms	ACTFS\|HDMX\|LSKB\|hdm2
	Cytomap	12q15
	Type of gene	protein-coding
	Description	E3 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, hum
	Modification date	20200329
	UniProtAcc	A0A0A8K972, A0A0A8K975, A0A0A8K978, A0A0A8K982, A0A0A8K986, A0A0A8K992, A0A0A8K9A1, A0A0A8K9A4, A0A0A8K9G1, A0A0A8K9G9, A0A0A8K9H4, A0A0A8K9H7, A0A0A8K9I1, A0A0A8KA03, A0A0A8KA06, A0A0A8KA17, A0A0A8KB67, A0A0A8KB70, A0A0A8KB75, A0A0A8KB78, A0A0A8KB88, A0A0A8KB92, A0A0A8KB97, A0A0A8KBA1, A0A0C4DFR5, A0A1B0GXJ6, A7UKX7, A7UKX8, A7UKX9, A7UKY0, A8WFP2, D0EKL1, E5RHE2, E5RJQ0, E7EMW5, E7EPE2, F5GWH7, F5GZB0, F5GZC3, F5H1M7, F5H4Q8, F6UXB6, G3XA89, J3KN53, J3QST1, Q00987, Q546E6, Q8NDV9, Q8NDW0, Q8NDW1, Q8NDW2, Q8TE47, Q8WYJ3, Q96DS0, Q96DS1, Q96DS2, Q96DS3, Q96DS4, Q96DS5, Q9H4C2, Q9H4C3, Q9H4C4, Q9H4C5,
	Context

Gene ontology of each this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Gene	GO ID	GO term	PubMed ID
MDM2	GO:0000122	negative regulation of transcription by RNA polymerase II	9271120\|17310983
MDM2	GO:0006511	ubiquitin-dependent protein catabolic process	11278372\|15314173\|16173922\|17310983
MDM2	GO:0016567	protein ubiquitination	9450543\|15878855\|19656744\|20153724
MDM2	GO:0031648	protein destabilization	9529249\|10360174\|15314173
MDM2	GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	11278372
MDM2	GO:0034504	protein localization to nucleus	10360174
MDM2	GO:0042176	regulation of protein catabolic process	9153395
MDM2	GO:0043518	negative regulation of DNA damage response, signal transduction by p53 class mediator	9529249\|10360174
MDM2	GO:0045184	establishment of protein localization	10360174
MDM2	GO:0045892	negative regulation of transcription, DNA-templated	9271120
MDM2	GO:0065003	protein-containing complex assembly	10608892\|12915590
MDM2	GO:0071157	negative regulation of cell cycle arrest	9529249
MDM2	GO:0071480	cellular response to gamma radiation	16213212
MDM2	GO:0072717	cellular response to actinomycin D	15314173
MDM2	GO:1901797	negative regulation of signal transduction by p53 class mediator	16173922

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Gene structures and expression levels for MDM2

Skipped exons in the ROSMAP, MSBB, and Mayo based on Ensembl gene isoform structure.
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

ENSG00000135679

Differentially expressed gene analysis across multiple brain tissues between AD and control.

Tissue type

DEG direction

Base mean exp.

log2FC(AD/control)

P-value

Adj. p-value

Differentially expressed isoform analysis across multiple brain tissues between AD and control.

Tissue type	DEG direction	ENST	Transcript info.	Base mean exp.	log2FC(AD/control)	P-value	Adjc. p-value
STG	UP	ENST00000393412.7	MDM2-209:protein_coding:MDM2	8.588281e+00	6.006057e+00	3.834439e-06	1.462170e-03
CB	DOWN	ENST00000540709.1	MDM2-227:lncRNA:MDM2	2.644682e+02	-9.138164e-01	1.083421e-13	2.425543e-11
CB	DOWN	ENST00000400501.2	MDM2-214:lncRNA:MDM2	2.290650e+01	-8.095693e-01	3.361642e-08	8.436505e-07
CB	UP	ENST00000258148.11	MDM2-201:protein_coding:MDM2	1.219505e+01	1.647610e+00	6.054607e-04	3.391537e-03

Landscape of isoform expressions across multiple brain tissues between AD and control.

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Exon skipping events with PSIs in ROSMAP, MSBB, and Mayo for MDM2

Landscape of individual exon skipping event across AD tissues and controls (PSI heatmap).

All exon skipping events in AD cohorts.

Exon skip ID	chr	Exons involved in exon skipping	Skipped exon
exon_skip_115652	chr12	68813602:68813628:68816812:68816945:68820325:68820374	68816812:68816945
exon_skip_168572	chr12	68813602:68813628:68814603:68814689:68816812:68816945	68814603:68814689
exon_skip_195945	chr12	68820325:68820374:68820885:68820910:68824363:68824430	68820885:68820910
exon_skip_197287	chr12	68813602:68813628:68815628:68815720:68816812:68816945	68815628:68815720
exon_skip_212410	chr12	68813554:68813628:68828771:68828931:68835829:68835984	68828771:68828931
exon_skip_250107	chr12	68809226:68809292:68813554:68813628:68820325:68820374	68813554:68813628
exon_skip_259125	chr12	68820325:68820374:68824363:68824430:68828771:68828810	68824363:68824430
exon_skip_28196	chr12	68824363:68824430:68824555:68824651:68828771:68828810	68824555:68824651
exon_skip_289406	chr12	68813554:68813628:68814603:68814689:68816812:68816945	68814603:68814689
exon_skip_29623	chr12	68824555:68824651:68828771:68828931:68835829:68835885	68828771:68828931
exon_skip_296546	chr12	68809226:68809292:68813554:68813628:68816812:68816945	68813554:68813628
exon_skip_4484	chr12	68820325:68820374:68823415:68823514:68824363:68824430	68823415:68823514
exon_skip_65737	chr12	68824555:68824651:68828771:68828931:68835829:68835984	68828771:68828931
exon_skip_95364	chr12	68835829:68835984:68836672:68836749:68839274:68839314	68836672:68836749

Differentially expressed PSI values of individual exon skipping events in multiple brain tissues between AD and control.

Exon skipping information

Tissue type

Avg(PSIs) in AD

Avg(PSIs) in control

Difference (PSI)

Adj. p-value

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Open reading frame (ORF) annotation in the exon skipping event for MDM2

Open reading frame (ORF) of individual exon skipping events in ROSMAP based on the Ensembl gene structure combined from isoforms.

ENST	Start of skipped exon	End of skipped exon	ORF
ENST00000539479	68816812	68816945	Frame-shift
ENST00000539479	68828771	68828931	Frame-shift

Open reading frame (ORF) of individual exon skipping events in MSBB based on the Ensembl gene structure combined from isoforms.

ENST	Start of skipped exon	End of skipped exon	ORF
ENST00000539479	68816812	68816945	Frame-shift
ENST00000539479	68828771	68828931	Frame-shift
ENST00000539479	68836672	68836749	In-frame

Open reading frame (ORF) of individual exon skipping events in Mayo based on the Ensembl gene structure combined from isoforms.

ENST	Start of skipped exon	End of skipped exon	ORF
ENST00000539479	68816812	68816945	Frame-shift
ENST00000539479	68824555	68824651	Frame-shift
ENST00000539479	68828771	68828931	Frame-shift
ENST00000539479	68813554	68813628	In-frame
ENST00000539479	68836672	68836749	In-frame

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Infer the effects of exon skipping event on protein functional features for MDM2

p-ENSG00000135679_img4.png
boxplot

Loci of skipped exons in ROSMAP across genomic, transcript, and protein sequence levels of In-frame cases.

ENST

Length of mRNA

Length of AA seq.

Genomic start

Genomic end

mRNA start

mRNA end

AA start

AA end

Loci of skipped exons in MSBB across genomic, transcript, and protein sequence levels of In-frame cases.

ENST	Length of mRNA	Length of AA seq.	Genomic start	Genomic end	mRNA start	mRNA end	AA start	AA end
ENST00000539479	2540	491	68836672	68836749	913	989	274	300

Loci of skipped exons in Mayo across genomic, transcript, and protein sequence levels of In-frame cases.

ENST	Length of mRNA	Length of AA seq.	Genomic start	Genomic end	mRNA start	mRNA end	AA start	AA end
ENST00000539479	2540	491	68813554	68813628	172	245	27	52
ENST00000539479	2540	491	68836672	68836749	913	989	274	300

Lost protein functional features of individual exon skipping events in ROSMAP.

UniProt acc.

Start of exon skipping (AA)

End of exon skipping (AA)

Protein feature start (AA)

Protein feature end (AA)

Category of protein feature

Description of feature

Lost protein functional features of individual exon skipping events in MSBB.

UniProt acc.	Start of exon skipping (AA)	End of exon skipping (AA)	Protein feature start (AA)	Protein feature end (AA)	Category of protein feature	Description of feature
Q00987	274	300	28	300	Alternative sequence	ID=VSP_003209;Note=In isoform Mdm2-B. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:8705862;Dbxref=PMID:8705862
Q00987	274	300	30	388	Alternative sequence	ID=VSP_003210;Note=In isoform Mdm2-D. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:8705862;Dbxref=PMID:8705862
Q00987	274	300	103	491	Alternative sequence	ID=VSP_003213;Note=In isoform Mdm2-E. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:8705862;Dbxref=PMID:8705862
Q00987	274	300	275	300	Alternative sequence	ID=VSP_003214;Note=In isoform Mdm2-A1. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:15315825;Dbxref=PMID:15315825
Q00987	274	300	295	297	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2C6A
Q00987	274	300	1	491	Chain	ID=PRO_0000157332;Note=E3 ubiquitin-protein ligase Mdm2
Q00987	274	300	243	301	Compositional bias	Note=Asp/Glu-rich (acidic)
Q00987	274	300	299	301	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:4XXB
Q00987	274	300	170	306	Region	Note=Interaction with MTBP;Ontology_term=ECO:0000250;evidence=ECO:0000250
Q00987	274	300	210	304	Region	Note=ARF-binding
Q00987	274	300	242	331	Region	Note=Region II
Q00987	274	300	276	491	Region	Note=Necessary for interaction with USP2
Q00987	274	300	299	328	Zinc finger	Note=RanBP2-type;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00322

Lost protein functional features of individual exon skipping events in Mayo.

UniProt acc.	Start of exon skipping (AA)	End of exon skipping (AA)	Protein feature start (AA)	Protein feature end (AA)	Category of protein feature	Description of feature
Q00987	27	52	1	61	Alternative sequence	ID=VSP_003207;Note=In isoform Mdm2-alpha. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:10597303;Dbxref=PMID:10597303
Q00987	27	52	28	300	Alternative sequence	ID=VSP_003209;Note=In isoform Mdm2-B. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:8705862;Dbxref=PMID:8705862
Q00987	27	52	28	222	Alternative sequence	ID=VSP_003208;Note=In isoform Mdm2-A and isoform Mdm2-A1. Missing;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:15315825,ECO:0000303\|PubMed:8705862;Dbxref=PMID:15315825,PMID:8705862
Q00987	27	52	30	388	Alternative sequence	ID=VSP_003210;Note=In isoform Mdm2-D. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:8705862;Dbxref=PMID:8705862
Q00987	27	52	27	30	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5C5A
Q00987	27	52	46	49	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:4OBA
Q00987	27	52	1	491	Chain	ID=PRO_0000157332;Note=E3 ubiquitin-protein ligase Mdm2
Q00987	27	52	27	107	Domain	Note=SWIB
Q00987	27	52	32	41	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5C5A
Q00987	27	52	50	64	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5C5A
Q00987	27	52	1	110	Region	Note=Necessary for interaction with USP2
Q00987	274	300	28	300	Alternative sequence	ID=VSP_003209;Note=In isoform Mdm2-B. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:8705862;Dbxref=PMID:8705862
Q00987	274	300	30	388	Alternative sequence	ID=VSP_003210;Note=In isoform Mdm2-D. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:8705862;Dbxref=PMID:8705862
Q00987	274	300	103	491	Alternative sequence	ID=VSP_003213;Note=In isoform Mdm2-E. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:8705862;Dbxref=PMID:8705862
Q00987	274	300	275	300	Alternative sequence	ID=VSP_003214;Note=In isoform Mdm2-A1. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:15315825;Dbxref=PMID:15315825
Q00987	274	300	295	297	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2C6A
Q00987	274	300	1	491	Chain	ID=PRO_0000157332;Note=E3 ubiquitin-protein ligase Mdm2
Q00987	274	300	243	301	Compositional bias	Note=Asp/Glu-rich (acidic)
Q00987	274	300	299	301	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:4XXB
Q00987	274	300	170	306	Region	Note=Interaction with MTBP;Ontology_term=ECO:0000250;evidence=ECO:0000250
Q00987	274	300	210	304	Region	Note=ARF-binding
Q00987	274	300	242	331	Region	Note=Region II
Q00987	274	300	276	491	Region	Note=Necessary for interaction with USP2
Q00987	274	300	299	328	Zinc finger	Note=RanBP2-type;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00322

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3'-UTR located exon skipping events that lost miRNA binding sites in MDM2

3'-UTR exon skipping evnets lost miRNA binding.

Tissue type

ENST

Exon skip start

Exon skip end

microRNA

Binding site by TargetScan

Binding type by TargetScan

Bdinding site by miRanda

Score of miRanda

Energy by miRanda

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SNVs in the skipped exons for MDM2

- Differential PSIs between mutated versus non-mutated samples.

- Depth of Coverage in the skipped exon of the mutated samples.

- Sashimi plot in the skipped exon of the mutated samples.

- Non-synonymous mutations located in the skipped exons.

Cancer type

Sample

ESID

Skipped exon start

Skipped exon end

Mutation start

Mutation end

Mutation type

Reference seq

Mutation seq

AAchange

- Non-synonymous mutations located in the skipped exons in CCLE.

Sample

Skipped exon start

Skipped exon end

Mutation start

Mutation end

Mutation type

Reference seq

Mutation seq

AAchange

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AD stage-associated exon skippint events for MDM2

Associated exon skipping events with Braak staging or Clinical Dementia Rating (CDR).

AD stage info

Cohort

Tissue

SE id

Coefficient

P-value

Chromosome

Strand

E1 start

E1 end

Skipped start

Skipped end

E2 start

E2 end

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Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for MDM2

sQTL information located at the skipped exons.

Tissue type

Exon skip ID

SNP id

Location

P-value

FDR

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Correlation with RNA binding proteins (RBPs) for MDM2

Correlated RBP and related information.

Tissue type

RBP name

Exon skip ID

Correlation coeifficient

P-value

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RelatedDrugs for MDM2

Approved drugs targeting this gene.
(DrugBank Version 5.1.0 2018-04-02)

UniProtAcc	DrugBank ID	Drug name	Drug activity	Drug type	Drug status
Q00987	approved\|investigational	DB01593	Zinc	small molecule	Q00987
Q00987	approved\|investigational	DB14487	Zinc acetate	small molecule	Q00987
Q00987	approved\|investigational	DB14533	Zinc chloride	small molecule	Q00987

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RelatedDiseases for MDM2

Diseases associated with this gene.
(DisGeNet 4.0)

Gene

Disease ID

Disease name

# pubmeds

Source

	Gene summary
	Gene structures and expression levels
	Exon skipping events with PSIs in RPSMAP, MSBB, and Mayo
	Open reading frame (ORF) annotation in the exon skipping event
	Exon skipping events in the canonical protein sequence
	3'-UTR located exon skipping events lost miRNA binding sites
	SNVs in the skipped exons with depth of coverage
	AD stage-associated exon skipping events
	Splicing Quantitative Trait Loci (sQTLs) in the skipped exons
	Correlation with RNA binding proteins (RBPs)
	Related drugs with this gene
	Related diseases with this gene

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Gene summary for MDM2

Gene structures and expression levels for MDM2

Exon skipping events with PSIs in ROSMAP, MSBB, and Mayo for MDM2

Open reading frame (ORF) annotation in the exon skipping event for MDM2

Infer the effects of exon skipping event on protein functional features for MDM2

3'-UTR located exon skipping events that lost miRNA binding sites in MDM2

SNVs in the skipped exons for MDM2

AD stage-associated exon skippint events for MDM2

Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for MDM2

Correlation with RNA binding proteins (RBPs) for MDM2

RelatedDrugs for MDM2

RelatedDiseases for MDM2