ExonSkipAD: functional annotation of exon skipping event in human

Gene summary for APPL1

Gene summary

Gene information	Gene symbol	APPL1
	Gene ID	26060
	Gene name	adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1
	Synonyms	APPL\|DIP13alpha\|MODY14
	Cytomap	3p14.3
	Type of gene	protein-coding
	Description	DCC-interacting protein 13-alphaAKT2 interactoradapter protein containing PH domain, PTB domain and leucine zipper motif 1adaptor protein containing pH domain, PTB domain and leucine zipper motif 1adaptor protein, phosphotyrosine interaction, PH domai
	Modification date	20200313
	UniProtAcc	C9JAB0, C9K0C4, Q9UKG1,
	Context

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

Gene	GO ID	GO term	PubMed ID
APPL1	GO:0006606	protein import into nucleus	26583432
APPL1	GO:2000045	regulation of G1/S transition of mitotic cell cycle	15016378

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Gene structures and expression levels for APPL1

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.

ENSG00000157500

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	DOWN	ENST00000464446.5	APPL1-203:retained_intron:APPL1	5.936284e+00	-9.042777e-01	2.729321e-03	2.978614e-02
CB	UP	ENST00000482800.5	APPL1-205:retained_intron:APPL1	7.329718e+01	1.132384e+00	1.748158e-15	9.008474e-13

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 APPL1

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_134297	chr3	57269541:57269751:57276304:57276459:57277793:57278105	57276304:57276459
exon_skip_200984	chr3	57252269:57252311:57253682:57253738:57256957:57257051	57253682:57253738
exon_skip_204568	chr3	57267742:57267792:57268398:57268487:57269541:57269751	57268398:57268487
exon_skip_218319	chr3	57227874:57227937:57230714:57230767:57235566:57235664	57230714:57230767
exon_skip_230668	chr3	57247395:57247477:57248193:57248351:57249360:57249548	57248193:57248351
exon_skip_247501	chr3	57247395:57247477:57248193:57248351:57249360:57249547	57248193:57248351
exon_skip_268027	chr3	57238045:57238116:57240465:57240552:57242101:57242142	57240465:57240552
exon_skip_27092	chr3	57260628:57260774:57267742:57267792:57268398:57268487	57267742:57267792
exon_skip_271473	chr3	57237492:57237551:57238045:57238116:57240465:57240552	57238045:57238116
exon_skip_286842	chr3	57240465:57240552:57242101:57242142:57242856:57242892	57242101:57242142
exon_skip_290574	chr3	57235566:57235664:57237492:57237551:57238045:57238116	57237492:57237551
exon_skip_29656	chr3	57242856:57242914:57246076:57246222:57247395:57247477	57246076:57246222
exon_skip_44444	chr3	57248193:57248351:57249360:57249548:57252269:57252311	57249360:57249548
exon_skip_9889	chr3	57227874:57227937:57235566:57235664:57237492:57237551	57235566:57235664

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 APPL1

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
ENST00000288266	57235566	57235664	In-frame
ENST00000288266	57237492	57237551	In-frame
ENST00000288266	57238045	57238116	In-frame
ENST00000288266	57246076	57246222	In-frame
ENST00000288266	57248193	57248351	In-frame
ENST00000288266	57249360	57249548	In-frame
ENST00000288266	57253682	57253738	In-frame
ENST00000288266	57267742	57267792	In-frame
ENST00000288266	57268398	57268487	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
ENST00000288266	57237492	57237551	In-frame
ENST00000288266	57248193	57248351	In-frame
ENST00000288266	57249360	57249548	In-frame
ENST00000288266	57267742	57267792	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
ENST00000288266	57240465	57240552	Frame-shift
ENST00000288266	57237492	57237551	In-frame
ENST00000288266	57242101	57242142	In-frame
ENST00000288266	57246076	57246222	In-frame
ENST00000288266	57248193	57248351	In-frame
ENST00000288266	57253682	57253738	In-frame
ENST00000288266	57267742	57267792	In-frame
ENST00000288266	57268398	57268487	In-frame

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Infer the effects of exon skipping event on protein functional features for APPL1

p-ENSG00000157500_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
ENST00000288266	6075	709	57235566	57235664	203	300	18	51
ENST00000288266	6075	709	57237492	57237551	302	360	51	71
ENST00000288266	6075	709	57238045	57238116	362	432	71	95
ENST00000288266	6075	709	57246076	57246222	623	768	158	207
ENST00000288266	6075	709	57248193	57248351	853	1010	235	287
ENST00000288266	6075	709	57249360	57249548	1012	1199	288	350
ENST00000288266	6075	709	57253682	57253738	1244	1299	365	384
ENST00000288266	6075	709	57267742	57267792	1991	2040	614	631

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
ENST00000288266	6075	709	57237492	57237551	302	360	51	71
ENST00000288266	6075	709	57248193	57248351	853	1010	235	287
ENST00000288266	6075	709	57249360	57249548	1012	1199	288	350
ENST00000288266	6075	709	57267742	57267792	1991	2040	614	631

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
ENST00000288266	6075	709	57237492	57237551	302	360	51	71
ENST00000288266	6075	709	57242101	57242142	522	562	125	138
ENST00000288266	6075	709	57246076	57246222	623	768	158	207
ENST00000288266	6075	709	57248193	57248351	853	1010	235	287
ENST00000288266	6075	709	57253682	57253738	1244	1299	365	384
ENST00000288266	6075	709	57267742	57267792	1991	2040	614	631

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
Q9UKG1	18	51	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	18	51	16	66	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	18	51	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	51	71	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	51	71	16	66	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	51	71	67	70	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	51	71	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	71	95	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	71	95	81	110	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	71	95	94	94	Natural variant	ID=VAR_075857;Note=In MODY14%3B no effect on protein abundance%3B loss of function in insulin receptor signaling pathway. D->N;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:26073777;Dbxref=dbSNP:rs796065047,PMID:26073777
Q9UKG1	71	95	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	158	207	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	158	207	157	217	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	158	207	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	235	287	262	265	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	235	287	281	286	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	235	287	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	235	287	215	259	Coiled coil	Ontology_term=ECO:0000255;evidence=ECO:0000255
Q9UKG1	235	287	277	375	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145
Q9UKG1	235	287	220	257	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	235	287	259	261	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	235	287	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	235	287	268	270	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	298	305	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	308	312	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	320	324	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	329	333	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	339	345	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	348	350	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2ELB
Q9UKG1	288	350	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	288	350	277	375	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145
Q9UKG1	288	350	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	365	384	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	365	384	277	375	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145
Q9UKG1	365	384	360	374	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	365	384	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	614	631	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	614	631	621	673	Coiled coil	Ontology_term=ECO:0000255;evidence=ECO:0000255
Q9UKG1	614	631	496	656	Domain	Note=PID;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00148
Q9UKG1	614	631	612	629	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2EJ8

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
Q9UKG1	51	71	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	51	71	16	66	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	51	71	67	70	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	51	71	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	235	287	262	265	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	235	287	281	286	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	235	287	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	235	287	215	259	Coiled coil	Ontology_term=ECO:0000255;evidence=ECO:0000255
Q9UKG1	235	287	277	375	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145
Q9UKG1	235	287	220	257	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	235	287	259	261	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	235	287	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	235	287	268	270	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	298	305	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	308	312	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	320	324	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	329	333	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	339	345	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	288	350	348	350	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2ELB
Q9UKG1	288	350	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	288	350	277	375	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145
Q9UKG1	288	350	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	614	631	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	614	631	621	673	Coiled coil	Ontology_term=ECO:0000255;evidence=ECO:0000255
Q9UKG1	614	631	496	656	Domain	Note=PID;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00148
Q9UKG1	614	631	612	629	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2EJ8

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
Q9UKG1	51	71	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	51	71	16	66	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	51	71	67	70	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	51	71	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	125	138	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	125	138	122	151	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	125	138	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	158	207	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	158	207	157	217	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	158	207	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	235	287	262	265	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	235	287	281	286	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	235	287	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	235	287	215	259	Coiled coil	Ontology_term=ECO:0000255;evidence=ECO:0000255
Q9UKG1	235	287	277	375	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145
Q9UKG1	235	287	220	257	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q12
Q9UKG1	235	287	259	261	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	235	287	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	235	287	268	270	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	365	384	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	365	384	277	375	Domain	Note=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00145
Q9UKG1	365	384	360	374	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2Q13
Q9UKG1	365	384	1	428	Region	Note=Required for RAB5A binding
Q9UKG1	614	631	1	709	Chain	ID=PRO_0000079985;Note=DCC-interacting protein 13-alpha
Q9UKG1	614	631	621	673	Coiled coil	Ontology_term=ECO:0000255;evidence=ECO:0000255
Q9UKG1	614	631	496	656	Domain	Note=PID;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00148
Q9UKG1	614	631	612	629	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:2EJ8

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3'-UTR located exon skipping events that lost miRNA binding sites in APPL1

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 APPL1

- 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 APPL1

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 APPL1

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 APPL1

Correlated RBP and related information.

Tissue type	RBP name	Exon skip ID	Correlation coeifficient	P-value
CB	CNOT4	exon_skip_290574	-6.000917e-01	2.363339e-15
CB	TRA2A	exon_skip_290574	-6.527217e-01	1.020202e-18
CB	NUP42	exon_skip_290574	5.531786e-01	7.809283e-13

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RelatedDrugs for APPL1

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 APPL1

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 APPL1

Gene structures and expression levels for APPL1

Exon skipping events with PSIs in ROSMAP, MSBB, and Mayo for APPL1

Open reading frame (ORF) annotation in the exon skipping event for APPL1

Infer the effects of exon skipping event on protein functional features for APPL1

3'-UTR located exon skipping events that lost miRNA binding sites in APPL1

SNVs in the skipped exons for APPL1

AD stage-associated exon skippint events for APPL1

Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for APPL1

Correlation with RNA binding proteins (RBPs) for APPL1

RelatedDrugs for APPL1

RelatedDiseases for APPL1