ExonSkipDB: functional annotation of exon skipping event in human

Gene summary for TK2

Gene summary

Gene information	Gene symbol	TK2
	Gene ID	7084
	Gene name	thymidine kinase 2, mitochondrial
	Synonyms	MTDPS2\|MTTK\|PEOB3\|SCA31
	Cytomap	16q21
	Type of gene	protein-coding
	Description	thymidine kinase 2, mitochondrialthymidine kinase 2mt-TK
	Modification date	20180523
	UniProtAcc	O00142
	Context	PubMed: TK2 [Title/Abstract] AND exon [Title/Abstract] AND skip [Title/Abstract] - Title (PMID)

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

Gene

GO ID

GO term

PubMed ID

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Exon skipping events across known transcript of Ensembl for TK2 from UCSC genome browser

Skipped exons in TCGA and GTEx 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.

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Gene isoform structures and expression levels for TK2

Expression levels of gene isoforms across TCGA.

Expression levels of gene isoforms across GTEx.

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Exon skipping events with PSIs in TCGA for TK2

Information of exkip skipping event in TCGA.

Exon skip ID	chr	Exons involved in exon skipping	Skipped exon	ENSG	ENSTs
exon_skip_145041	16	66551691:66551780:66562896:66562970:66565282:66565372	66562896:66562970	ENSG00000166548.11	ENST00000562484.2,ENST00000525974.1,ENST00000417693.3,ENST00000527284.1,ENST00000563369.2,ENST00000545043.2,ENST00000567357.1,ENST00000564917.1,ENST00000451102.2,ENST00000527800.1,ENST00000299697.7,ENST00000563478.1,ENST00000544898.1
exon_skip_145043	16	66562896:66562970:66565282:66565372:66570866:66570920	66565282:66565372	ENSG00000166548.11	ENST00000562484.2,ENST00000525974.1,ENST00000527284.1,ENST00000563369.2,ENST00000545043.2,ENST00000567357.1,ENST00000564917.1,ENST00000451102.2,ENST00000527800.1,ENST00000569718.1,ENST00000299697.7,ENST00000563478.1,ENST00000544898.1
exon_skip_145044	16	66565282:66565372:66570866:66570920:66575781:66575856	66570866:66570920	ENSG00000166548.11	ENST00000562484.2,ENST00000525974.1,ENST00000527284.1,ENST00000563369.2,ENST00000567357.1,ENST00000564917.1,ENST00000451102.2,ENST00000527800.1,ENST00000569718.1,ENST00000299697.7,ENST00000563478.1,ENST00000544898.1
exon_skip_145045	16	66570866:66570920:66575781:66575856:66582880:66582912	66575781:66575856	ENSG00000166548.11	ENST00000562484.2,ENST00000525974.1,ENST00000527284.1,ENST00000563369.2,ENST00000564917.1,ENST00000451102.2,ENST00000527800.1,ENST00000569718.1,ENST00000299697.7,ENST00000563478.1
exon_skip_145048	16	66575781:66575856:66581873:66581968:66582880:66582912	66581873:66581968	ENSG00000166548.11	ENST00000567357.1,ENST00000544898.1

PSI values of skipped exons in TCGA.

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Exon skipping events with PSIs in GTEx for TK2

Information of exkip skipping event in GTEx

Exon skip ID	chr	Exons involved in exon skipping	Skipped exon	ENSG	ENSTs
exon_skip_145041	16	66551691:66551780:66562896:66562970:66565282:66565372	66562896:66562970	ENSG00000166548.11	ENST00000299697.7,ENST00000451102.2,ENST00000527800.1,ENST00000527284.1,ENST00000567357.1,ENST00000544898.1,ENST00000545043.2,ENST00000564917.1,ENST00000525974.1,ENST00000417693.3,ENST00000563369.2,ENST00000563478.1,ENST00000562484.2
exon_skip_145043	16	66562896:66562970:66565282:66565372:66570866:66570920	66565282:66565372	ENSG00000166548.11	ENST00000299697.7,ENST00000451102.2,ENST00000527800.1,ENST00000527284.1,ENST00000567357.1,ENST00000544898.1,ENST00000545043.2,ENST00000564917.1,ENST00000525974.1,ENST00000569718.1,ENST00000563369.2,ENST00000563478.1,ENST00000562484.2
exon_skip_145044	16	66565282:66565372:66570866:66570920:66575781:66575856	66570866:66570920	ENSG00000166548.11	ENST00000299697.7,ENST00000451102.2,ENST00000527800.1,ENST00000527284.1,ENST00000567357.1,ENST00000544898.1,ENST00000564917.1,ENST00000525974.1,ENST00000569718.1,ENST00000563369.2,ENST00000563478.1,ENST00000562484.2
exon_skip_145045	16	66570866:66570920:66575781:66575856:66582880:66582912	66575781:66575856	ENSG00000166548.11	ENST00000299697.7,ENST00000451102.2,ENST00000527800.1,ENST00000527284.1,ENST00000564917.1,ENST00000525974.1,ENST00000569718.1,ENST00000563369.2,ENST00000563478.1,ENST00000562484.2
exon_skip_145048	16	66575781:66575856:66581873:66581968:66582880:66582912	66581873:66581968	ENSG00000166548.11	ENST00000567357.1,ENST00000544898.1

PSI values of skipped exons in GTEx.

* Skipped exon sequences.

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Open reading frame (ORF) annotation in the exon skipping event for TK2

Open reading frame (ORF) of individual exon skipping events in TCGA based on the Ensembl gene structure combined from isoforms.

ENST	Start of skipped exon	End of skipped exon	ORF
ENST00000544898	66581873	66581968	3UTR-3CDS
ENST00000299697	66562896	66562970	Frame-shift
ENST00000544898	66562896	66562970	Frame-shift
ENST00000299697	66565282	66565372	In-frame
ENST00000544898	66565282	66565372	In-frame
ENST00000299697	66570866	66570920	In-frame
ENST00000544898	66570866	66570920	In-frame
ENST00000299697	66575781	66575856	In-frame

Open reading frame (ORF) of individual exon skipping events in GTEx based on the Ensembl gene structure combined from isoforms.

ENST	Start of skipped exon	End of skipped exon	ORF
ENST00000544898	66581873	66581968	3UTR-3CDS
ENST00000299697	66562896	66562970	Frame-shift
ENST00000544898	66562896	66562970	Frame-shift
ENST00000299697	66565282	66565372	In-frame
ENST00000544898	66565282	66565372	In-frame
ENST00000299697	66570866	66570920	In-frame
ENST00000544898	66570866	66570920	In-frame
ENST00000299697	66575781	66575856	In-frame

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Infer the effects of exon skipping event on protein functional features for TK2

Exon skipping at the protein sequence level and followed lost functional features.
* Click on the image to enlarge it in a new window.

Loci of skipped exons in TCGA 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
ENST00000544898	2283	265	66570866	66570920	479	532	28	46
ENST00000544898	2283	265	66565282	66565372	533	622	46	76
ENST00000299697	5131	265	66575781	66575856	508	582	94	119
ENST00000299697	5131	265	66570866	66570920	583	636	119	137
ENST00000299697	5131	265	66565282	66565372	637	726	137	167

Loci of skipped exons in GTEx 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
ENST00000544898	2283	265	66570866	66570920	479	532	28	46
ENST00000544898	2283	265	66565282	66565372	533	622	46	76
ENST00000299697	5131	265	66575781	66575856	508	582	94	119
ENST00000299697	5131	265	66570866	66570920	583	636	119	137
ENST00000299697	5131	265	66565282	66565372	637	726	137	167

Lost protein functional features of individual exon skipping events in TCGA.

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
O00142	28	46	1	97	Alternative sequence	ID=VSP_054606;Note=In isoform 5. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
O00142	28	46	1	41	Alternative sequence	ID=VSP_003028;Note=In isoform 2. MLLWPLRGWAARALRCFGPGSRGSPASGPGPRRVQRRAWPP->MGAFCQRPSS;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:9079672;Dbxref=PMID:9079672
O00142	28	46	34	265	Chain	ID=PRO_0000016842;Note=Thymidine kinase 2%2C mitochondrial
O00142	28	46	37	37	Sequence conflict	Note=R->Y;Ontology_term=ECO:0000305;evidence=ECO:0000305
O00142	28	46	1	33	Transit peptide	Note=Mitochondrion
O00142	46	76	1	97	Alternative sequence	ID=VSP_054606;Note=In isoform 5. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
O00142	46	76	53	77	Alternative sequence	ID=VSP_043503;Note=In isoform 3. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
O00142	46	76	34	265	Chain	ID=PRO_0000016842;Note=Thymidine kinase 2%2C mitochondrial
O00142	46	76	53	53	Natural variant	ID=VAR_019419;Note=In MTDPS2. I->M;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12391347;Dbxref=dbSNP:rs137854432,PMID:12391347
O00142	46	76	64	64	Natural variant	ID=VAR_023790;Note=In MTDPS2. T->M;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15907288;Dbxref=dbSNP:rs281865487,PMID:15907288
O00142	46	76	57	65	Nucleotide binding	Note=ATP;Ontology_term=ECO:0000250;evidence=ECO:0000250
O00142	46	76	49	49	Sequence conflict	Note=K->E;Ontology_term=ECO:0000305;evidence=ECO:0000305
O00142	46	76	61	61	Sequence conflict	Note=S->G;Ontology_term=ECO:0000305;evidence=ECO:0000305
O00142	94	119	1	97	Alternative sequence	ID=VSP_054606;Note=In isoform 5. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
O00142	94	119	78	95	Alternative sequence	ID=VSP_044459;Note=In isoform 4. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
O00142	94	119	99	99	Binding site	Note=Substrate;Ontology_term=ECO:0000250;evidence=ECO:0000250
O00142	94	119	110	110	Binding site	Note=Substrate;Ontology_term=ECO:0000250;evidence=ECO:0000250
O00142	94	119	34	265	Chain	ID=PRO_0000016842;Note=Thymidine kinase 2%2C mitochondrial
O00142	94	119	108	108	Natural variant	ID=VAR_019420;Note=In MTDPS2%3B reduction of activity. T->M;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:12391347,ECO:0000269\|PubMed:15639197;Dbxref=dbSNP:rs137854431,PMID:12391347,PMID:15639197
O00142	94	119	117	117	Natural variant	ID=VAR_072789;Note=In MTDPS2%3B severe form of combined brain and muscular atrophy%3B depletion of mtDNA in skeletal muscle%3B normal residual mtDNA in blood and fibroblasts. M->V;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:25446393;Dbxref=PMID:
O00142	119	137	133	133	Active site	Note=Proton acceptor;Ontology_term=ECO:0000255;evidence=ECO:0000255
O00142	119	137	134	134	Binding site	Note=Substrate;Ontology_term=ECO:0000250;evidence=ECO:0000250
O00142	119	137	34	265	Chain	ID=PRO_0000016842;Note=Thymidine kinase 2%2C mitochondrial
O00142	119	137	121	121	Natural variant	ID=VAR_019421;Note=In MTDPS2%3B reduction of activity in muscles. H->N;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11687801,ECO:0000269\|PubMed:12391347;Dbxref=dbSNP:rs137854429,PMID:11687801,PMID:12391347
O00142	137	167	34	265	Chain	ID=PRO_0000016842;Note=Thymidine kinase 2%2C mitochondrial
O00142	137	167	139	139	Natural variant	ID=VAR_072790;Note=In MTDPS2%3B severe form of combined brain and muscular atrophy%3B depletion of mtDNA in skeletal muscle%3B normal residual mtDNA in blood and fibroblasts. A->V;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:25446393;Dbxref=dbSNP

Lost protein functional features of individual exon skipping events in GTEx.

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
O00142	28	46	1	97	Alternative sequence	ID=VSP_054606;Note=In isoform 5. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
O00142	28	46	1	41	Alternative sequence	ID=VSP_003028;Note=In isoform 2. MLLWPLRGWAARALRCFGPGSRGSPASGPGPRRVQRRAWPP->MGAFCQRPSS;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:9079672;Dbxref=PMID:9079672
O00142	28	46	34	265	Chain	ID=PRO_0000016842;Note=Thymidine kinase 2%2C mitochondrial
O00142	28	46	37	37	Sequence conflict	Note=R->Y;Ontology_term=ECO:0000305;evidence=ECO:0000305
O00142	28	46	1	33	Transit peptide	Note=Mitochondrion
O00142	46	76	1	97	Alternative sequence	ID=VSP_054606;Note=In isoform 5. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
O00142	46	76	53	77	Alternative sequence	ID=VSP_043503;Note=In isoform 3. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
O00142	46	76	34	265	Chain	ID=PRO_0000016842;Note=Thymidine kinase 2%2C mitochondrial
O00142	46	76	53	53	Natural variant	ID=VAR_019419;Note=In MTDPS2. I->M;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12391347;Dbxref=dbSNP:rs137854432,PMID:12391347
O00142	46	76	64	64	Natural variant	ID=VAR_023790;Note=In MTDPS2. T->M;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15907288;Dbxref=dbSNP:rs281865487,PMID:15907288
O00142	46	76	57	65	Nucleotide binding	Note=ATP;Ontology_term=ECO:0000250;evidence=ECO:0000250
O00142	46	76	49	49	Sequence conflict	Note=K->E;Ontology_term=ECO:0000305;evidence=ECO:0000305
O00142	46	76	61	61	Sequence conflict	Note=S->G;Ontology_term=ECO:0000305;evidence=ECO:0000305
O00142	94	119	1	97	Alternative sequence	ID=VSP_054606;Note=In isoform 5. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
O00142	94	119	78	95	Alternative sequence	ID=VSP_044459;Note=In isoform 4. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
O00142	94	119	99	99	Binding site	Note=Substrate;Ontology_term=ECO:0000250;evidence=ECO:0000250
O00142	94	119	110	110	Binding site	Note=Substrate;Ontology_term=ECO:0000250;evidence=ECO:0000250
O00142	94	119	34	265	Chain	ID=PRO_0000016842;Note=Thymidine kinase 2%2C mitochondrial
O00142	94	119	108	108	Natural variant	ID=VAR_019420;Note=In MTDPS2%3B reduction of activity. T->M;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:12391347,ECO:0000269\|PubMed:15639197;Dbxref=dbSNP:rs137854431,PMID:12391347,PMID:15639197
O00142	94	119	117	117	Natural variant	ID=VAR_072789;Note=In MTDPS2%3B severe form of combined brain and muscular atrophy%3B depletion of mtDNA in skeletal muscle%3B normal residual mtDNA in blood and fibroblasts. M->V;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:25446393;Dbxref=PMID:
O00142	119	137	133	133	Active site	Note=Proton acceptor;Ontology_term=ECO:0000255;evidence=ECO:0000255
O00142	119	137	134	134	Binding site	Note=Substrate;Ontology_term=ECO:0000250;evidence=ECO:0000250
O00142	119	137	34	265	Chain	ID=PRO_0000016842;Note=Thymidine kinase 2%2C mitochondrial
O00142	119	137	121	121	Natural variant	ID=VAR_019421;Note=In MTDPS2%3B reduction of activity in muscles. H->N;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11687801,ECO:0000269\|PubMed:12391347;Dbxref=dbSNP:rs137854429,PMID:11687801,PMID:12391347
O00142	137	167	34	265	Chain	ID=PRO_0000016842;Note=Thymidine kinase 2%2C mitochondrial
O00142	137	167	139	139	Natural variant	ID=VAR_072790;Note=In MTDPS2%3B severe form of combined brain and muscular atrophy%3B depletion of mtDNA in skeletal muscle%3B normal residual mtDNA in blood and fibroblasts. A->V;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:25446393;Dbxref=dbSNP

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SNVs in the skipped exons for TK2

- Lollipop plot for presenting exon skipping associated SNVs.
* Click on the image to enlarge it in a new window.

- Differential PSIs between mutated versus non-mutated samples.

- Non-synonymous mutations located in the skipped exons in TCGA.

Cancer type	Sample	ESID	Skipped exon start	Skipped exon end	Mutation start	Mutation end	Mutation type	Reference seq	Mutation seq	AAchange
CHOL	TCGA-ZH-A8Y4-01	exon_skip_145041	66562897	66562970	66562916	66562917	Frame_Shift_Ins	-	A	p.R186fs

- Depth of coverage in the three exons composing exon skipping event

Depth of coverage in three exons

Mutation description

- 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
CHLA218_BONE	66565283	66565372	66565335	66565335	Missense_Mutation	G	A	p.T108M
NCIH211_LUNG	66570867	66570920	66570901	66570901	Missense_Mutation	G	A	p.S84F
BICR18_UPPER_AERODIGESTIVE_TRACT	66570867	66570920	66570901	66570901	Missense_Mutation	G	A	p.S84F
BICR18_UPPER_AERODIGESTIVE_TRACT	66570867	66570920	66570902	66570902	Missense_Mutation	A	G	p.S84P
BICR18_UPPER_AERODIGESTIVE_TRACT	66570867	66570920	66570913	66570913	Missense_Mutation	G	A	p.T80M
SKMEL28_SKIN	66575782	66575856	66575795	66575795	Missense_Mutation	G	A	p.A73V
DND41_HAEMATOPOIETIC_AND_LYMPHOID_TISSUE	66575782	66575856	66575834	66575834	Missense_Mutation	G	A	p.A60V

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Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for TK2

sQTL information located at the skipped exons.

Exon skip ID

Chromosome

Three exons

Skippped exon

ENST

Cancer type

SNP id

Location

DNA change (ref/var)

P-value

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Splicing Quantitative Trait Methylation (sQTM) in the skipped exon for TK2

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Survival analysis of Splicing Quantitative Trait Methylation (sQTM) in the skipped exon for TK2

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RelatedDrugs for TK2

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

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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RelatedDiseases for TK2

Diseases associated with this gene.
(DisGeNet 4.0)

Gene	Disease ID	Disease name	# pubmeds	Source
TK2	C3149750	MITOCHONDRIAL DNA DEPLETION SYNDROME 2 (MYOPATHIC TYPE)	6	CTD_human;ORPHANET;UNIPROT

	Gene summary
	Gene structures and expression levels
	Exon skipping events with PSIs in TCGA
	Exon skipping events with PSIs in GTEx
	Open reading frame (ORF) annotation in the exon skipping event
	Exon skipping events in the canonical protein sequence
	SNVs in the skipped exons with depth of coverage
	Splicing Quantitative Trait Loci (sQTLs) in the skipped exons
	Splicing Quantitative Trait Methylation (sQTM) in the skipped exon
	Related drugs with this gene
	Related diseases with this gene

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