ExonSkipAD: functional annotation of exon skipping event in human

Gene summary for PAK1

Gene summary

Gene information	Gene symbol	PAK1
	Gene ID	5058
	Gene name	p21 (RAC1) activated kinase 1
	Synonyms	IDDMSSD\|PAKalpha\|alpha-PAK\|p65-PAK
	Cytomap	11q13.5-q14.1
	Type of gene	protein-coding
	Description	serine/threonine-protein kinase PAK 1STE20 homolog, yeastp21 protein (Cdc42/Rac)-activated kinase 1p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)p21/Cdc42/Rac1-activated kinase 1 (yeast Ste20-related)
	Modification date	20200327
	UniProtAcc	A0A024R5P0, B3KNX7, E9PJF8, E9PKH9, E9PM17, E9PMP2, E9PQW5, E9PRP6, H0YCG5, H0YCM0, H0YF55, Q13153,
	Context	- 18466762(ROCK, PAK, and Toll of Synapses in Alzheimer's Disease)

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

Gene	GO ID	GO term	PubMed ID
PAK1	GO:0000165	MAPK cascade	8805275
PAK1	GO:0006338	chromatin remodeling	23260667
PAK1	GO:0006468	protein phosphorylation	9852149\|23260667
PAK1	GO:0006974	cellular response to DNA damage stimulus	23260667
PAK1	GO:0030335	positive regulation of cell migration	25766321
PAK1	GO:0031532	actin cytoskeleton reorganization	9395435
PAK1	GO:0033138	positive regulation of peptidyl-serine phosphorylation	19667065
PAK1	GO:0033148	positive regulation of intracellular estrogen receptor signaling pathway	16278681
PAK1	GO:0046777	protein autophosphorylation	8805275

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Gene structures and expression levels for PAK1

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.

ENSG00000149269

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
CB	UP	ENST00000527457.5	PAK1-208:nonsense_mediated_decay:PAK1	5.193313e+00	2.290234e+00	9.065460e-08	1.951612e-06

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 PAK1

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_100504	chr11	77358898:77359017:77374328:77374365:77379241:77379351	77374328:77374365
exon_skip_104539	chr11	77323269:77323360:77332730:77332867:77336086:77336259	77332730:77332867
exon_skip_127111	chr11	77392331:77392538:77397027:77397093:77411774:77411904	77397027:77397093
exon_skip_135201	chr11	77379917:77379994:77392331:77392541:77411774:77411904	77392331:77392541
exon_skip_142238	chr11	77392510:77392538:77397027:77397093:77411774:77411904	77397027:77397093
exon_skip_159055	chr11	77392331:77392541:77455881:77455937:77473552:77473735	77455881:77455937
exon_skip_167794	chr11	77349248:77349287:77353536:77353599:77355668:77355742	77353536:77353599
exon_skip_171514	chr11	77329151:77329312:77332730:77332867:77336086:77336282	77332730:77332867
exon_skip_179859	chr11	77325328:77325376:77332730:77332867:77336086:77336259	77332730:77332867
exon_skip_188892	chr11	77392443:77392541:77397027:77397158:77411774:77411933	77397027:77397158
exon_skip_193107	chr11	77336254:77336282:77337324:77337423:77340646:77340763	77337324:77337423
exon_skip_207408	chr11	77349248:77349287:77353536:77353599:77355668:77355842	77353536:77353599
exon_skip_217263	chr11	77353536:77353599:77355668:77355842:77358898:77358953	77355668:77355842
exon_skip_228628	chr11	77379383:77379388:77379894:77379994:77392331:77392383	77379894:77379994
exon_skip_238515	chr11	77379917:77379994:77392331:77392541:77473552:77473735	77392331:77392541
exon_skip_250397	chr11	77392510:77392541:77397027:77397158:77411774:77411904	77397027:77397158
exon_skip_278967	chr11	77323269:77323360:77325328:77325376:77332730:77332867	77325328:77325376
exon_skip_288292	chr11	77340646:77340763:77343819:77343931:77349239:77349287	77343819:77343931
exon_skip_291956	chr11	77340646:77340763:77355668:77355842:77358898:77358953	77355668:77355842
exon_skip_35700	chr11	77392331:77392541:77408154:77408232:77411774:77411904	77408154:77408232
exon_skip_48747	chr11	77343819:77343931:77349239:77349287:77358898:77358953	77349239:77349287
exon_skip_63000	chr11	77392443:77392541:77397027:77397158:77411774:77411904	77397027:77397158
exon_skip_73541	chr11	77323269:77323360:77332730:77332867:77336086:77336282	77332730:77332867
exon_skip_91285	chr11	77392443:77392541:77455881:77455937:77473552:77473735	77455881:77455937
exon_skip_94046	chr11	77392443:77392541:77408154:77408232:77411774:77411933	77408154:77408232

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 PAK1

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
ENST00000356341	77337324	77337423	Frame-shift
ENST00000356341	77343819	77343931	Frame-shift
ENST00000356341	77353536	77353599	Frame-shift
ENST00000356341	77374328	77374365	Frame-shift
ENST00000356341	77379894	77379994	Frame-shift
ENST00000356341	77332730	77332867	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
ENST00000356341	77337324	77337423	Frame-shift
ENST00000356341	77343819	77343931	Frame-shift
ENST00000356341	77353536	77353599	Frame-shift
ENST00000356341	77379894	77379994	Frame-shift
ENST00000356341	77332730	77332867	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
ENST00000356341	77337324	77337423	Frame-shift
ENST00000356341	77343819	77343931	Frame-shift
ENST00000356341	77353536	77353599	Frame-shift
ENST00000356341	77355668	77355842	Frame-shift
ENST00000356341	77374328	77374365	Frame-shift
ENST00000356341	77379894	77379994	Frame-shift
ENST00000356341	77332730	77332867	In-frame

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Infer the effects of exon skipping event on protein functional features for PAK1

p-ENSG00000149269_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
ENST00000356341	3754	545	77332730	77332867	1946	2082	471	516

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
ENST00000356341	3754	545	77332730	77332867	1946	2082	471	516

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
ENST00000356341	3754	545	77332730	77332867	1946	2082	471	516

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
Q13153	471	516	2	545	Chain	ID=PRO_0000086460;Note=Serine/threonine-protein kinase PAK 1
Q13153	471	516	270	521	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Q13153	471	516	469	479	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	487	489	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	492	501	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	512	515	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	515	515	Natural variant	ID=VAR_051654;Note=L->V;Dbxref=dbSNP:rs35345144
Q13153	471	516	503	503	Sequence conflict	Note=E->D;Ontology_term=ECO:0000305;evidence=ECO:0000305
Q13153	471	516	506	508	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ

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
Q13153	471	516	2	545	Chain	ID=PRO_0000086460;Note=Serine/threonine-protein kinase PAK 1
Q13153	471	516	270	521	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Q13153	471	516	469	479	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	487	489	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	492	501	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	512	515	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	515	515	Natural variant	ID=VAR_051654;Note=L->V;Dbxref=dbSNP:rs35345144
Q13153	471	516	503	503	Sequence conflict	Note=E->D;Ontology_term=ECO:0000305;evidence=ECO:0000305
Q13153	471	516	506	508	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ

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
Q13153	471	516	2	545	Chain	ID=PRO_0000086460;Note=Serine/threonine-protein kinase PAK 1
Q13153	471	516	270	521	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Q13153	471	516	469	479	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	487	489	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	492	501	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	512	515	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ
Q13153	471	516	515	515	Natural variant	ID=VAR_051654;Note=L->V;Dbxref=dbSNP:rs35345144
Q13153	471	516	503	503	Sequence conflict	Note=E->D;Ontology_term=ECO:0000305;evidence=ECO:0000305
Q13153	471	516	506	508	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3FXZ

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3'-UTR located exon skipping events that lost miRNA binding sites in PAK1

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 PAK1

- 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 PAK1

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

CDR

MSBB

IFG

exon_skip_73541

4.179076e-01

2.690275e-02

chr11

77323269

77323360

77332730

77332867

77336086

77336282

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Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for PAK1

sQTL information located at the skipped exons.

Tissue type	Exon skip ID	SNP id	Location	P-value	FDR
CB	exon_skip_127111	rs10899380	chr11:77483556	1.911517e-04	2.882831e-02
CB	exon_skip_127111	rs2250647	chr11:77358701	2.224768e-04	3.247700e-02
CB	exon_skip_127111	rs6592723	chr11:77484437	2.938474e-04	3.989824e-02
PCC	exon_skip_127111	rs2602477	chr11:77436425	6.031362e-06	1.637002e-03
PCC	exon_skip_127111	rs2250647	chr11:77358701	8.664248e-06	2.239456e-03
PCC	exon_skip_127111	rs2729753	chr11:77366229	1.220899e-05	3.018304e-03
PCC	exon_skip_127111	rs6592723	chr11:77484437	1.739258e-05	4.112550e-03
PCC	exon_skip_127111	rs2602458	chr11:77428002	3.139108e-05	6.738078e-03
PCC	exon_skip_127111	rs2602472	chr11:77357109	3.414372e-05	7.214128e-03
PCC	exon_skip_127111	rs7109645	chr11:77475278	7.485566e-05	1.367063e-02
PCC	exon_skip_127111	rs10899380	chr11:77483556	7.485566e-05	1.367063e-02
PCC	exon_skip_127111	rs12225060	chr11:77484466	7.485566e-05	1.367063e-02
PCC	exon_skip_127111	rs2844336	chr11:77370680	8.992815e-05	1.583552e-02

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Correlation with RNA binding proteins (RBPs) for PAK1

Correlated RBP and related information.

Tissue type	RBP name	Exon skip ID	Correlation coeifficient	P-value
CB	SRSF2	exon_skip_200016	4.322428e-01	5.964205e-07
CB	RBM6	exon_skip_200016	-4.424126e-01	3.000513e-07
CB	PCBP4	exon_skip_200016	5.586082e-01	1.894652e-11
CB	TRA2A	exon_skip_200016	-5.173602e-01	8.948270e-10
CB	RBM45	exon_skip_200016	6.426583e-01	1.119323e-15
CB	HNRNPD	exon_skip_200016	4.298682e-01	6.979599e-07
CB	NUP42	exon_skip_200016	5.930101e-01	4.946873e-13
CB	RALYL	exon_skip_200016	4.018512e-01	4.085751e-06
CB	SRSF9	exon_skip_200016	4.015320e-01	4.165091e-06
IFG	SRSF2	exon_skip_127111	4.930088e-01	2.315603e-02
IFG	TRA2A	exon_skip_77540	-4.164743e-01	2.748494e-02
IFG	PCBP2	exon_skip_77540	-4.153761e-01	2.793786e-02

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RelatedDrugs for PAK1

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

UniProtAcc	DrugBank ID	Drug name	Drug activity	Drug type	Drug status
Q13153	approved\|investigational	DB12010	Fostamatinib	small molecule	Q13153

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RelatedDiseases for PAK1

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 PAK1

Gene structures and expression levels for PAK1

Exon skipping events with PSIs in ROSMAP, MSBB, and Mayo for PAK1

Open reading frame (ORF) annotation in the exon skipping event for PAK1

Infer the effects of exon skipping event on protein functional features for PAK1

3'-UTR located exon skipping events that lost miRNA binding sites in PAK1

SNVs in the skipped exons for PAK1

AD stage-associated exon skippint events for PAK1

Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for PAK1

Correlation with RNA binding proteins (RBPs) for PAK1

RelatedDrugs for PAK1

RelatedDiseases for PAK1