ExonSkipAD: functional annotation of exon skipping event in human

Gene summary for SORL1

Gene summary

Gene information	Gene symbol	SORL1
	Gene ID	6653
	Gene name	sortilin related receptor 1
	Synonyms	C11orf32\|LR11\|LRP9\|SORLA\|SorLA-1\|gp250
	Cytomap	11q24.1
	Type of gene	protein-coding
	Description	sortilin-related receptorLDLR relative with 11 ligand-binding repeatslow-density lipoprotein receptor relative with 11 ligand-binding repeatsmosaic protein LR11sortilin-related receptor, L(DLR class) A repeats containingsorting protein-related recept
	Modification date	20200327
	UniProtAcc	A0A024R3H2, E9PKB0, E9PP43, E9PPB3, E9PS32, L8EA23, Q92673,
	Context	- 32492427(Depletion of the AD Risk Gene SORL1 Selectively Impairs Neuronal Endosomal Traffic Independent of Amyloidogenic APP Processing)

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

Gene	GO ID	GO term	PubMed ID
SORL1	GO:0006605	protein targeting	16407538\|21385844\|27322061
SORL1	GO:0006622	protein targeting to lysosome	24523320
SORL1	GO:0006892	post-Golgi vesicle-mediated transport	17855360
SORL1	GO:0014910	regulation of smooth muscle cell migration	14764453
SORL1	GO:0032091	negative regulation of protein binding	16407538
SORL1	GO:0034067	protein localization to Golgi apparatus	17855360
SORL1	GO:0038020	insulin receptor recycling	27322061
SORL1	GO:0045053	protein retention in Golgi apparatus	17855360
SORL1	GO:0045732	positive regulation of protein catabolic process	24523320
SORL1	GO:0046628	positive regulation of insulin receptor signaling pathway	27322061
SORL1	GO:0051604	protein maturation	17855360
SORL1	GO:1900168	positive regulation of glial cell-derived neurotrophic factor secretion	21994944
SORL1	GO:1902430	negative regulation of amyloid-beta formation	16407538\|22621900
SORL1	GO:1902960	negative regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process	16407538
SORL1	GO:1904179	positive regulation of adipose tissue development	27322061

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Gene structures and expression levels for SORL1

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.

ENSG00000137642

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	ENST00000532694.5	SORL1-211:protein_coding:SORL1	7.925869e+00	9.097597e-01	7.773030e-06	8.538995e-05
CB	UP	ENST00000527934.1	SORL1-206:protein_coding:SORL1	2.426148e+00	8.507432e-01	4.318224e-03	1.744777e-02
CB	UP	ENST00000529445.1	SORL1-208:retained_intron:SORL1	1.025962e+00	9.730671e-01	7.533760e-03	2.756516e-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 SORL1

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_101815	chr11	121545243:121545429:121549960:121550088:121550585:121550670	121549960:121550088
exon_skip_127447	chr11	121488032:121488193:121490043:121490110:121496869:121497049	121490043:121490110
exon_skip_136157	chr11	121607190:121607290:121608104:121608176:121611076:121611158	121608104:121608176
exon_skip_138750	chr11	121452380:121452616:121470007:121470123:121478118:121478243	121470007:121470123
exon_skip_142740	chr11	121595623:121595772:121604193:121604324:121605113:121605239	121604193:121604324
exon_skip_188914	chr11	121574241:121574363:121577281:121577400:121583458:121583583	121577281:121577400
exon_skip_219197	chr11	121555187:121555318:121557314:121557405:121558591:121558773	121557314:121557405
exon_skip_225270	chr11	121478118:121478243:121488032:121488193:121490043:121490110	121488032:121488193
exon_skip_244417	chr11	121566940:121567113:121570157:121570270:121574241:121574363	121570157:121570270
exon_skip_263846	chr11	121607186:121607290:121608104:121608176:121611076:121611158	121608104:121608176
exon_skip_3521	chr11	121608104:121608176:121611076:121611158:121612736:121612832	121611076:121611158
exon_skip_72955	chr11	121522586:121522703:121522916:121522989:121532464:121532552	121522916:121522989
exon_skip_86523	chr11	121470007:121470123:121478118:121478243:121488032:121488193	121478118:121478243

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 SORL1

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
ENST00000260197	121490043	121490110	Frame-shift
ENST00000260197	121522916	121522989	Frame-shift
ENST00000260197	121557314	121557405	Frame-shift
ENST00000260197	121611076	121611158	Frame-shift
ENST00000260197	121478118	121478243	In-frame
ENST00000260197	121549960	121550088	In-frame
ENST00000260197	121570157	121570270	In-frame
ENST00000260197	121577281	121577400	In-frame
ENST00000260197	121604193	121604324	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
ENST00000260197	121557314	121557405	Frame-shift
ENST00000260197	121488032	121488193	In-frame
ENST00000260197	121549960	121550088	In-frame
ENST00000260197	121570157	121570270	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
ENST00000260197	121490043	121490110	Frame-shift
ENST00000260197	121522916	121522989	Frame-shift
ENST00000260197	121557314	121557405	Frame-shift
ENST00000260197	121608104	121608176	Frame-shift
ENST00000260197	121611076	121611158	Frame-shift
ENST00000260197	121604193	121604324	In-frame

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Infer the effects of exon skipping event on protein functional features for SORL1

p-ENSG00000137642_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
ENST00000260197	10921	2214	121478118	121478243	533	657	134	176
ENST00000260197	10921	2214	121549960	121550088	2182	2309	684	726
ENST00000260197	10921	2214	121570157	121570270	3354	3466	1075	1112
ENST00000260197	10921	2214	121577281	121577400	3591	3709	1154	1193
ENST00000260197	10921	2214	121604193	121604324	4650	4780	1507	1550

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
ENST00000260197	10921	2214	121488032	121488193	659	819	176	230
ENST00000260197	10921	2214	121549960	121550088	2182	2309	684	726
ENST00000260197	10921	2214	121570157	121570270	3354	3466	1075	1112

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
ENST00000260197	10921	2214	121604193	121604324	4650	4780	1507	1550

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
Q92673	134	176	133	140	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	134	176	145	147	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSY
Q92673	134	176	164	169	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	134	176	82	2214	Chain	ID=PRO_0000033165;Note=Sortilin-related receptor
Q92673	134	176	158	158	Glycosylation	Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255
Q92673	134	176	149	151	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	134	176	141	141	Natural variant	ID=VAR_070012;Note=In AD%3B unknown pathological significance. Y->C;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:22472873;Dbxref=PMID:22472873
Q92673	134	176	136	147	Repeat	Note=BNR 1
Q92673	134	176	82	2137	Topological domain	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255
Q92673	684	726	682	684	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	688	690	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	699	701	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	722	724	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	82	2214	Chain	ID=PRO_0000033165;Note=Sortilin-related receptor
Q92673	684	726	694	696	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	703	705	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	82	2137	Topological domain	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255
Q92673	1075	1112	82	2214	Chain	ID=PRO_0000033165;Note=Sortilin-related receptor
Q92673	1075	1112	1078	1090	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1075	1112	1085	1103	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1075	1112	1097	1112	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1075	1112	1076	1114	Domain	Note=LDL-receptor class A 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1075	1112	82	2137	Topological domain	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255
Q92673	1154	1193	82	2214	Chain	ID=PRO_0000033165;Note=Sortilin-related receptor
Q92673	1154	1193	1158	1170	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1154	1193	1165	1183	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1154	1193	1177	1192	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1154	1193	1115	1155	Domain	Note=LDL-receptor class A 2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1154	1193	1156	1194	Domain	Note=LDL-receptor class A 3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1154	1193	1164	1164	Glycosylation	Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255
Q92673	1154	1193	1191	1191	Glycosylation	Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255
Q92673	1154	1193	82	2137	Topological domain	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255
Q92673	1507	1550	82	2214	Chain	ID=PRO_0000033165;Note=Sortilin-related receptor
Q92673	1507	1550	1514	1527	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1507	1550	1521	1540	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1507	1550	1534	1549	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1507	1550	1469	1508	Domain	Note=LDL-receptor class A 10;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1507	1550	1512	1551	Domain	Note=LDL-receptor class A 11;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1507	1550	82	2137	Topological domain	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255

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
Q92673	176	230	177	192	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	176	230	198	201	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	176	230	207	211	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	176	230	219	223	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	176	230	230	236	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	176	230	82	2214	Chain	ID=PRO_0000033165;Note=Sortilin-related receptor
Q92673	176	230	82	2137	Topological domain	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255
Q92673	684	726	682	684	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	688	690	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	699	701	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	722	724	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	82	2214	Chain	ID=PRO_0000033165;Note=Sortilin-related receptor
Q92673	684	726	694	696	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	703	705	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3WSX
Q92673	684	726	82	2137	Topological domain	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255
Q92673	1075	1112	82	2214	Chain	ID=PRO_0000033165;Note=Sortilin-related receptor
Q92673	1075	1112	1078	1090	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1075	1112	1085	1103	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1075	1112	1097	1112	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1075	1112	1076	1114	Domain	Note=LDL-receptor class A 1;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1075	1112	82	2137	Topological domain	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255

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
Q92673	1507	1550	82	2214	Chain	ID=PRO_0000033165;Note=Sortilin-related receptor
Q92673	1507	1550	1514	1527	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1507	1550	1521	1540	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1507	1550	1534	1549	Disulfide bond	Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1507	1550	1469	1508	Domain	Note=LDL-receptor class A 10;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1507	1550	1512	1551	Domain	Note=LDL-receptor class A 11;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00124
Q92673	1507	1550	82	2137	Topological domain	Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255

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3'-UTR located exon skipping events that lost miRNA binding sites in SORL1

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 SORL1

- 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 SORL1

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 SORL1

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 SORL1

Correlated RBP and related information.

Tissue type

RBP name

Exon skip ID

Correlation coeifficient

P-value

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RelatedDrugs for SORL1

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 SORL1

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 SORL1

Gene structures and expression levels for SORL1

Exon skipping events with PSIs in ROSMAP, MSBB, and Mayo for SORL1

Open reading frame (ORF) annotation in the exon skipping event for SORL1

Infer the effects of exon skipping event on protein functional features for SORL1

3'-UTR located exon skipping events that lost miRNA binding sites in SORL1

SNVs in the skipped exons for SORL1

AD stage-associated exon skippint events for SORL1

Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for SORL1

Correlation with RNA binding proteins (RBPs) for SORL1

RelatedDrugs for SORL1

RelatedDiseases for SORL1