ExonSkipAD: functional annotation of exon skipping event in human

Gene summary for DLD

Gene summary

Gene information	Gene symbol	DLD
	Gene ID	1738
	Gene name	dihydrolipoamide dehydrogenase
	Synonyms	DLDD\|DLDH\|E3\|GCSL\|LAD\|PHE3
	Cytomap	7q31.1
	Type of gene	protein-coding
	Description	dihydrolipoyl dehydrogenase, mitochondrialE3 component of pyruvate dehydrogenase complex, 2-oxo-glutarate complex, branched chain keto acid dehydrogenase complexdiaphoraseepididymis secretory sperm binding proteinglycine cleavage system L proteinglyc
	Modification date	20200313
	UniProtAcc	A0A024R713, A0A1W2PR83, E9PEX6, F2Z2E3, F8WDM5, F8WDY5, P09622,
	Context	- 30056470(Dihydrolipoamide dehydrogenase suppression induces human tau phosphorylation by increasing whole body glucose levels in a C elegans model of 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
DLD	GO:0106077	histone succinylation	29211711

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Gene structures and expression levels for DLD

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.

ENSG00000091140

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	ENST00000415325.5	DLD-202:nonsense_mediated_decay:DLD	2.100480e+02	9.525822e-01	6.845527e-06	7.651909e-05
CB	UP	ENST00000451081.5	DLD-207:nonsense_mediated_decay:DLD	6.986485e+00	1.014363e+00	3.634690e-04	2.202803e-03
CB	UP	ENST00000453354.5	DLD-208:lncRNA:DLD	2.286725e+00	1.036693e+00	1.173560e-02	3.961334e-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 DLD

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_127622	chr7	107893200:107893278:107901738:107901817:107903478:107903547	107901738:107901817
exon_skip_144131	chr7	107893236:107893278:107901738:107901817:107902325:107902393	107901738:107901817
exon_skip_161127	chr7	107893236:107893278:107901738:107901817:107903478:107903547	107901738:107901817
exon_skip_226261	chr7	107903503:107903547:107904958:107905058:107905361:107905389	107904958:107905058
exon_skip_233043	chr7	107906271:107906368:107915506:107915696:107916794:107916964	107915506:107915696
exon_skip_234351	chr7	107903503:107903547:107904958:107905058:107906267:107906368	107904958:107905058
exon_skip_239927	chr7	107891217:107891289:107893200:107893278:107903478:107903547	107893200:107893278
exon_skip_245423	chr7	107891217:107891289:107893200:107893278:107901738:107901817	107893200:107893278
exon_skip_247537	chr7	107917924:107918061:107919010:107919099:107919194:107919383	107919010:107919099
exon_skip_276100	chr7	107901738:107901817:107902325:107902393:107903478:107903547	107902325:107902393
exon_skip_287990	chr7	107904958:107905058:107905361:107905504:107906267:107906368	107905361:107905504
exon_skip_31642	chr7	107903503:107903547:107904863:107905058:107905361:107905389	107904863:107905058

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 DLD

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
ENST00000205402	107902325	107902393	In-frame
ENST00000205402	107905361	107905504	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

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
ENST00000205402	107893200	107893278	Frame-shift
ENST00000205402	107901738	107901817	Frame-shift
ENST00000205402	107904958	107905058	Frame-shift
ENST00000205402	107915506	107915696	Frame-shift
ENST00000205402	107902325	107902393	In-frame
ENST00000205402	107905361	107905504	In-frame
ENST00000205402	107919010	107919099	In-frame

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

p-ENSG00000091140_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
ENST00000205402	3772	509	107902325	107902393	481	548	66	89
ENST00000205402	3772	509	107905361	107905504	721	863	146	194

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

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
ENST00000205402	3772	509	107902325	107902393	481	548	66	89
ENST00000205402	3772	509	107905361	107905504	721	863	146	194
ENST00000205402	3772	509	107919010	107919099	1657	1745	458	488

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
P09622	66	89	1	99	Alternative sequence	ID=VSP_055855;Note=In isoform 2. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
P09622	66	89	67	71	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	66	89	73	77	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	66	89	89	89	Binding site	Note=FAD;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15946682;Dbxref=PMID:15946682
P09622	66	89	36	509	Chain	ID=PRO_0000030295;Note=Dihydrolipoyl dehydrogenase%2C mitochondrial
P09622	66	89	80	85	Disulfide bond	Note=Redox-active;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:P09624
P09622	66	89	78	83	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	66	89	85	102	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	66	89	66	66	Modified residue	Note=N6-acetyllysine%3B alternate;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:O08749
P09622	66	89	66	66	Modified residue	Note=N6-succinyllysine%3B alternate;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:O08749
P09622	66	89	89	89	Mutagenesis	Note=Abolishes dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX. K->E;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20160912;Dbxref=PMID:20160912
P09622	66	89	72	72	Natural variant	ID=VAR_006907;Note=In DLDD%3B reduced dihydrolipoyl dehydrogenase activity%3B no effect on interaction with PDHX. K->E;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:20160912,ECO:0000269\|PubMed:8506365;Dbxref=dbSNP:rs121964987,PMID:2016
P09622	66	89	71	80	Nucleotide binding	Note=FAD;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15946682;Dbxref=PMID:15946682
P09622	146	194	147	194	Alternative sequence	ID=VSP_055856;Note=In isoform 3. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
P09622	146	194	148	158	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	146	194	161	165	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	146	194	171	181	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	146	194	185	187	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	146	194	154	154	Binding site	Note=FAD%3B via amide nitrogen and carbonyl oxygen;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15946682;Dbxref=PMID:15946682
P09622	146	194	36	509	Chain	ID=PRO_0000030295;Note=Dihydrolipoyl dehydrogenase%2C mitochondrial
P09622	146	194	159	159	Modified residue	Note=N6-succinyllysine;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:O08749
P09622	146	194	166	166	Modified residue	Note=N6-succinyllysine;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:O08749
P09622	146	194	183	185	Nucleotide binding	Note=FAD;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15946682;Dbxref=PMID:15946682
P09622	146	194	154	154	Sequence conflict	Note=G->R;Ontology_term=ECO:0000305;evidence=ECO:0000305

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

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
P09622	66	89	1	99	Alternative sequence	ID=VSP_055855;Note=In isoform 2. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
P09622	66	89	67	71	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	66	89	73	77	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	66	89	89	89	Binding site	Note=FAD;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15946682;Dbxref=PMID:15946682
P09622	66	89	36	509	Chain	ID=PRO_0000030295;Note=Dihydrolipoyl dehydrogenase%2C mitochondrial
P09622	66	89	80	85	Disulfide bond	Note=Redox-active;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:P09624
P09622	66	89	78	83	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	66	89	85	102	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	66	89	66	66	Modified residue	Note=N6-acetyllysine%3B alternate;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:O08749
P09622	66	89	66	66	Modified residue	Note=N6-succinyllysine%3B alternate;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:O08749
P09622	66	89	89	89	Mutagenesis	Note=Abolishes dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX. K->E;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20160912;Dbxref=PMID:20160912
P09622	66	89	72	72	Natural variant	ID=VAR_006907;Note=In DLDD%3B reduced dihydrolipoyl dehydrogenase activity%3B no effect on interaction with PDHX. K->E;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:20160912,ECO:0000269\|PubMed:8506365;Dbxref=dbSNP:rs121964987,PMID:2016
P09622	66	89	71	80	Nucleotide binding	Note=FAD;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15946682;Dbxref=PMID:15946682
P09622	146	194	147	194	Alternative sequence	ID=VSP_055856;Note=In isoform 3. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
P09622	146	194	148	158	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	146	194	161	165	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	146	194	171	181	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	146	194	185	187	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	146	194	154	154	Binding site	Note=FAD%3B via amide nitrogen and carbonyl oxygen;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15946682;Dbxref=PMID:15946682
P09622	146	194	36	509	Chain	ID=PRO_0000030295;Note=Dihydrolipoyl dehydrogenase%2C mitochondrial
P09622	146	194	159	159	Modified residue	Note=N6-succinyllysine;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:O08749
P09622	146	194	166	166	Modified residue	Note=N6-succinyllysine;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:O08749
P09622	146	194	183	185	Nucleotide binding	Note=FAD;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15946682;Dbxref=PMID:15946682
P09622	146	194	154	154	Sequence conflict	Note=G->R;Ontology_term=ECO:0000305;evidence=ECO:0000305
P09622	458	488	487	487	Active site	Note=Proton acceptor;Ontology_term=ECO:0000250;evidence=ECO:0000250\|UniProtKB:P09624
P09622	458	488	36	509	Chain	ID=PRO_0000030295;Note=Dihydrolipoyl dehydrogenase%2C mitochondrial
P09622	458	488	460	473	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	458	488	477	482	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:5J5Z
P09622	458	488	466	466	Mutagenesis	Note=Decreases dehydrogenase activity. Loss of proteolytic activity. E->A;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:17404228;Dbxref=PMID:17404228
P09622	458	488	473	473	Mutagenesis	Note=Reduces interaction with PDHX. Inhibits multienzyme pyruvate dehydrogenase complex activity. Does not affect dihydrolipoyl dehydrogenase activity. Y->A;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20385101;Dbxref=PMID:20385101
P09622	458	488	473	473	Mutagenesis	Note=Does not affect dihydrolipoyl dehydrogenase activity. Y->F;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20385101;Dbxref=PMID:20385101
P09622	458	488	473	473	Mutagenesis	Note=Reduces interaction with PDHX. Inhibits multienzyme pyruvate dehydrogenase complex activity. Does not affect dihydrolipoyl dehydrogenase activity. Y->H;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20385101;Dbxref=PMID:20385101
P09622	458	488	482	482	Mutagenesis	Note=Does not affect dihydrolipoyl dehydrogenase activity. R->A;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20385101;Dbxref=PMID:20385101
P09622	458	488	482	482	Mutagenesis	Note=Does not affect interaction with PDHX. R->M;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20160912;Dbxref=PMID:20160912
P09622	458	488	485	485	Mutagenesis	Note=Loss of dehydrogenase activity. Increases proteolytic activity. H->A;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:17404228;Dbxref=PMID:17404228
P09622	458	488	479	479	Natural variant	ID=VAR_076990;Note=In DLDD%3B reduced dehydrogenase activity%3B increased proteolytic activity. D->V;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10448086,ECO:0000269\|PubMed:17404228;Dbxref=dbSNP:rs397514649,PMID:10448086,PMID:1740422
P09622	458	488	482	482	Natural variant	ID=VAR_076991;Note=In DLDD%3B reduced enzyme activity. R->G;Dbxref=dbSNP:rs397514650
P09622	458	488	488	488	Natural variant	ID=VAR_006908;Note=In DLDD%3B no effect on interaction with PDHX. P->L;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:20160912,ECO:0000269\|PubMed:8506365;Dbxref=dbSNP:rs121964988,PMID:20160912,PMID:8506365
P09622	458	488	473	473	Site	Note=Important for interaction with PDHX and activity of multienzyme pyruvate dehydrogenase complex;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20385101;Dbxref=PMID:20385101

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

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 DLD

- 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 DLD

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 DLD

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 DLD

Correlated RBP and related information.

Tissue type

RBP name

Exon skip ID

Correlation coeifficient

P-value

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RelatedDrugs for DLD

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 DLD

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 DLD

Gene structures and expression levels for DLD

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

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

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

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

SNVs in the skipped exons for DLD

AD stage-associated exon skippint events for DLD

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

Correlation with RNA binding proteins (RBPs) for DLD

RelatedDrugs for DLD

RelatedDiseases for DLD