ExonSkipAD: functional annotation of exon skipping event in human

Gene summary for USP15

Gene summary

Gene information	Gene symbol	USP15
	Gene ID	9958
	Gene name	ubiquitin specific peptidase 15
	Synonyms	UNPH-2\|UNPH4
	Cytomap	12q14.1
	Type of gene	protein-coding
	Description	ubiquitin carboxyl-terminal hydrolase 15deubiquitinating enzyme 15ubiquitin thioesterase 15ubiquitin thiolesterase 15ubiquitin-specific-processing protease 15
	Modification date	20200313
	UniProtAcc	F8VVY7, F8VZG8, F8W0H4, H0YH96, H0YHM4, H0YI26, H0YI31, Q2NL66, Q9Y4E8,
	Context

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

Gene	GO ID	GO term	PubMed ID
USP15	GO:0007179	transforming growth factor beta receptor signaling pathway	21947082
USP15	GO:0016579	protein deubiquitination	16005295\|22344298\|27368102
USP15	GO:0030509	BMP signaling pathway	21947082
USP15	GO:0035520	monoubiquitinated protein deubiquitination	21947082\|24399297
USP15	GO:0035616	histone H2B conserved C-terminal lysine deubiquitination	24526689
USP15	GO:1900246	positive regulation of RIG-I signaling pathway	24399297

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Gene structures and expression levels for USP15

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.

ENSG00000135655

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
PG	UP	ENST00000548836.1	USP15-210:protein_coding:USP15	2.813379e+00	3.677067e+00	1.345577e-04	3.416258e-03
CB	DOWN	ENST00000398084.6	DUSP15-205:protein_coding:DUSP15	4.708181e+01	-8.251003e-01	7.683871e-08	1.700805e-06
CB	DOWN	ENST00000486996.5	DUSP15-209:protein_coding:DUSP15	2.214913e+01	-1.102652e+00	5.845338e-07	9.497398e-06
CB	UP	ENST00000549268.1	USP15-213:retained_intron:USP15	6.608322e+01	9.181415e-01	1.610807e-05	1.579447e-04
CB	UP	ENST00000550632.5	USP15-216:lncRNA:USP15	3.665931e+01	1.525388e+00	4.825268e-04	2.795385e-03
CB	UP	ENST00000546718.5	USP15-206:retained_intron:USP15	5.925474e-01	1.338040e+00	6.150347e-04	3.436426e-03
CB	UP	ENST00000549415.1	USP15-214:protein_coding:USP15	1.158471e+01	9.223007e-01	2.091324e-03	9.567039e-03
CB	DOWN	ENST00000375966.8	DUSP15-203:protein_coding:DUSP15	1.395287e+01	-1.636141e+00	5.378545e-03	2.091160e-02
TC	DOWN	ENST00000375966.8	DUSP15-203:protein_coding:DUSP15	3.111560e+01	-1.255750e+00	1.110066e-03	1.072490e-02

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 USP15

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_142330	chr12	62321464:62321609:62325872:62325933:62355331:62355386	62325872:62325933
exon_skip_163649	chr12	62325872:62325933:62349221:62349307:62355331:62355386	62349221:62349307
exon_skip_19963	chr12	62314790:62314916:62321464:62321609:62355331:62355386	62321464:62321609
exon_skip_207688	chr12	62321464:62321609:62325872:62325933:62349221:62349307	62325872:62325933
exon_skip_217180	chr12	62302790:62302920:62314790:62314916:62321464:62321489	62314790:62314916
exon_skip_229181	chr12	62355428:62355475:62381490:62381663:62383840:62383998	62381490:62381663
exon_skip_43296	chr12	62389431:62389514:62389605:62389699:62389797:62389873	62389605:62389699
exon_skip_65418	chr12	62302790:62302920:62312286:62312309:62314790:62314916	62312286:62312309
exon_skip_81262	chr12	62355428:62355475:62374390:62374535:62381490:62381633	62374390:62374535
exon_skip_82541	chr12	62325872:62325933:62355331:62355475:62381490:62381633	62355331:62355475
exon_skip_93428	chr12	62314790:62314916:62321464:62321609:62325872:62325933	62321464:62321609

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
exon_skip_163649	Mayo_CB	3.528205e-01	4.561017e-01	-1.032812e-01	1.151263e-06

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Open reading frame (ORF) annotation in the exon skipping event for USP15

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
ENST00000280377	62325872	62325933	Frame-shift
ENST00000280377	62349221	62349307	In-frame

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
ENST00000280377	62321464	62321609	Frame-shift
ENST00000280377	62325872	62325933	Frame-shift
ENST00000280377	62349221	62349307	In-frame
ENST00000280377	62381490	62381663	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
ENST00000280377	62314790	62314916	Frame-shift
ENST00000280377	62321464	62321609	Frame-shift
ENST00000280377	62325872	62325933	Frame-shift
ENST00000280377	62389605	62389699	Frame-shift
ENST00000280377	62349221	62349307	In-frame

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Infer the effects of exon skipping event on protein functional features for USP15

p-ENSG00000135655_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
ENST00000280377	4765	981	62349221	62349307	743	828	228	256

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
ENST00000280377	4765	981	62349221	62349307	743	828	228	256
ENST00000280377	4765	981	62381490	62381663	975	1147	305	363

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
ENST00000280377	4765	981	62349221	62349307	743	828	228	256

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
Q9Y4E8	228	256	217	256	Alternative sequence	ID=VSP_005260;Note=In isoform 3. DGTWPRGPSTPKSPGASNFSTLPKISPSSLSNNYNNMNNR->QKNEDGTWPRGPSTP;Ontology_term=ECO:0000303;evidence=ECO:0000303\|Ref.9
Q9Y4E8	228	256	228	256	Alternative sequence	ID=VSP_005261;Note=In isoform 2. Missing;Ontology_term=ECO:0000303,ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:15489334,ECO:0000303\|PubMed:9628581,ECO:0000303\|Ref.1;Dbxref=PMID:15489334,PMID:9628581
Q9Y4E8	228	256	229	235	Alternative sequence	ID=VSP_045165;Note=In isoform 4. SPGASNF->KPLEQSC;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:14702039,ECO:0000303\|PubMed:15489334;Dbxref=PMID:14702039,PMID:15489334
Q9Y4E8	228	256	236	981	Alternative sequence	ID=VSP_045166;Note=In isoform 4. Missing;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:14702039,ECO:0000303\|PubMed:15489334;Dbxref=PMID:14702039,PMID:15489334
Q9Y4E8	228	256	2	981	Chain	ID=PRO_0000080641;Note=Ubiquitin carboxyl-terminal hydrolase 15
Q9Y4E8	228	256	229	229	Modified residue	Note=Phosphoserine;Ontology_term=ECO:0000244,ECO:0000244,ECO:0000244,ECO:0000244,ECO:0000244,ECO:0000244;evidence=ECO:0000244\|PubMed:16964243,ECO:0000244\|PubMed:18669648,ECO:0000244\|PubMed:19690332,ECO:0000244\|PubMed:20068231,ECO:0000244\|PubMed:21406692,E
Q9Y4E8	228	256	242	242	Modified residue	Note=Phosphoserine;Ontology_term=ECO:0000244,ECO:0000244;evidence=ECO:0000244\|PubMed:20068231,ECO:0000244\|PubMed:23186163;Dbxref=PMID:20068231,PMID:23186163

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
Q9Y4E8	228	256	217	256	Alternative sequence	ID=VSP_005260;Note=In isoform 3. DGTWPRGPSTPKSPGASNFSTLPKISPSSLSNNYNNMNNR->QKNEDGTWPRGPSTP;Ontology_term=ECO:0000303;evidence=ECO:0000303\|Ref.9
Q9Y4E8	228	256	228	256	Alternative sequence	ID=VSP_005261;Note=In isoform 2. Missing;Ontology_term=ECO:0000303,ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:15489334,ECO:0000303\|PubMed:9628581,ECO:0000303\|Ref.1;Dbxref=PMID:15489334,PMID:9628581
Q9Y4E8	228	256	229	235	Alternative sequence	ID=VSP_045165;Note=In isoform 4. SPGASNF->KPLEQSC;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:14702039,ECO:0000303\|PubMed:15489334;Dbxref=PMID:14702039,PMID:15489334
Q9Y4E8	228	256	236	981	Alternative sequence	ID=VSP_045166;Note=In isoform 4. Missing;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:14702039,ECO:0000303\|PubMed:15489334;Dbxref=PMID:14702039,PMID:15489334
Q9Y4E8	228	256	2	981	Chain	ID=PRO_0000080641;Note=Ubiquitin carboxyl-terminal hydrolase 15
Q9Y4E8	228	256	229	229	Modified residue	Note=Phosphoserine;Ontology_term=ECO:0000244,ECO:0000244,ECO:0000244,ECO:0000244,ECO:0000244,ECO:0000244;evidence=ECO:0000244\|PubMed:16964243,ECO:0000244\|PubMed:18669648,ECO:0000244\|PubMed:19690332,ECO:0000244\|PubMed:20068231,ECO:0000244\|PubMed:21406692,E
Q9Y4E8	228	256	242	242	Modified residue	Note=Phosphoserine;Ontology_term=ECO:0000244,ECO:0000244;evidence=ECO:0000244\|PubMed:20068231,ECO:0000244\|PubMed:23186163;Dbxref=PMID:20068231,PMID:23186163
Q9Y4E8	305	363	236	981	Alternative sequence	ID=VSP_045166;Note=In isoform 4. Missing;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:14702039,ECO:0000303\|PubMed:15489334;Dbxref=PMID:14702039,PMID:15489334
Q9Y4E8	305	363	2	981	Chain	ID=PRO_0000080641;Note=Ubiquitin carboxyl-terminal hydrolase 15
Q9Y4E8	305	363	289	933	Domain	Note=USP;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU01035

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
Q9Y4E8	228	256	217	256	Alternative sequence	ID=VSP_005260;Note=In isoform 3. DGTWPRGPSTPKSPGASNFSTLPKISPSSLSNNYNNMNNR->QKNEDGTWPRGPSTP;Ontology_term=ECO:0000303;evidence=ECO:0000303\|Ref.9
Q9Y4E8	228	256	228	256	Alternative sequence	ID=VSP_005261;Note=In isoform 2. Missing;Ontology_term=ECO:0000303,ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:15489334,ECO:0000303\|PubMed:9628581,ECO:0000303\|Ref.1;Dbxref=PMID:15489334,PMID:9628581
Q9Y4E8	228	256	229	235	Alternative sequence	ID=VSP_045165;Note=In isoform 4. SPGASNF->KPLEQSC;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:14702039,ECO:0000303\|PubMed:15489334;Dbxref=PMID:14702039,PMID:15489334
Q9Y4E8	228	256	236	981	Alternative sequence	ID=VSP_045166;Note=In isoform 4. Missing;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303\|PubMed:14702039,ECO:0000303\|PubMed:15489334;Dbxref=PMID:14702039,PMID:15489334
Q9Y4E8	228	256	2	981	Chain	ID=PRO_0000080641;Note=Ubiquitin carboxyl-terminal hydrolase 15
Q9Y4E8	228	256	229	229	Modified residue	Note=Phosphoserine;Ontology_term=ECO:0000244,ECO:0000244,ECO:0000244,ECO:0000244,ECO:0000244,ECO:0000244;evidence=ECO:0000244\|PubMed:16964243,ECO:0000244\|PubMed:18669648,ECO:0000244\|PubMed:19690332,ECO:0000244\|PubMed:20068231,ECO:0000244\|PubMed:21406692,E
Q9Y4E8	228	256	242	242	Modified residue	Note=Phosphoserine;Ontology_term=ECO:0000244,ECO:0000244;evidence=ECO:0000244\|PubMed:20068231,ECO:0000244\|PubMed:23186163;Dbxref=PMID:20068231,PMID:23186163

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3'-UTR located exon skipping events that lost miRNA binding sites in USP15

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 USP15

- 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 USP15

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

ADstage

MSBB

IFG

exon_skip_163649

4.535553e-01

1.534665e-02

chr12

62325872

62325933

62349221

62349307

62355331

62355386

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Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for USP15

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 USP15

Correlated RBP and related information.

Tissue type	RBP name	Exon skip ID	Correlation coeifficient	P-value
CB	DAZAP1	exon_skip_163649	-4.071499e-01	7.911389e-07
CB	RBM6	exon_skip_163649	-4.360066e-01	1.006770e-07
CB	U2AF2	exon_skip_163649	-6.347803e-01	8.122433e-17
CB	CNOT4	exon_skip_163649	-5.601632e-01	1.101878e-12
CB	FUBP1	exon_skip_163649	-4.783032e-01	3.395656e-09
CB	HNRNPC	exon_skip_163649	-5.650368e-01	6.358107e-13
IFG	ELAVL4	exon_skip_163649	-4.982180e-01	6.971624e-03
IFG	KHDRBS3	exon_skip_163649	-4.548230e-01	1.502731e-02
IFG	RALYL	exon_skip_163649	-4.965700e-01	7.190884e-03
PCC	ESRP2	exon_skip_81262	4.012001e-01	5.624556e-09
STG	ELAVL4	exon_skip_81262	-4.316005e-01	7.146566e-05

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RelatedDrugs for USP15

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

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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RelatedDiseases for USP15

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 USP15

Gene structures and expression levels for USP15

Exon skipping events with PSIs in ROSMAP, MSBB, and Mayo for USP15

Open reading frame (ORF) annotation in the exon skipping event for USP15

Infer the effects of exon skipping event on protein functional features for USP15

3'-UTR located exon skipping events that lost miRNA binding sites in USP15

SNVs in the skipped exons for USP15

AD stage-associated exon skippint events for USP15

Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for USP15

Correlation with RNA binding proteins (RBPs) for USP15

RelatedDrugs for USP15

RelatedDiseases for USP15