Mutagenetix > Incidental Mutation

Incidental Mutation 'R8454:Tk2'

654937

Institutional Source

Beutler Lab

Gene Symbol

Tk2

Ensembl Gene

ENSMUSG00000035824

Gene Name

thymidine kinase 2, mitochondrial

Synonyms

MMRRC Submission

067831-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.742) question?

Stock #

R8454 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

104953317-104975190 bp(-) (GRCm39)

Type of Mutation

critical splice donor site (2 bp from exon)

DNA Base Change (assembly)

A to G at 104967746 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000053616 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000050211] [ENSMUST00000211995] [ENSMUST00000212209] [ENSMUST00000212275] [ENSMUST00000212854]

AlphaFold

no structure available at present

Predicted Effect

probably null
Transcript: ENSMUST00000050211

SMART Domains

Protein: ENSMUSP00000053616
Gene: ENSMUSG00000035824

Domain	Start	End	E-Value	Type
low complexity region	2	35	N/A	INTRINSIC
Pfam:dNK	58	267	1.2e-67	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000211995

Predicted Effect

probably benign
Transcript: ENSMUST00000212209

Predicted Effect

probably null
Transcript: ENSMUST00000212275

Predicted Effect

probably benign
Transcript: ENSMUST00000212854

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a deoxyribonucleoside kinase that specifically phosphorylates thymidine, deoxycytidine, and deoxyuridine. The encoded enzyme localizes to the mitochondria and is required for mitochondrial DNA synthesis. Mutations in this gene are associated with a myopathic form of mitochondrial DNA depletion syndrome. Alternate splicing results in multiple transcript variants encoding distinct isoforms, some of which lack transit peptide, so are not localized to mitochondria. [provided by RefSeq, Dec 2012]
PHENOTYPE: Knock-out mice die at 2-4 wks of age showing stunted growth, hypothermia, progressive mtDNA loss, aberrant myocardial fibers and altered adipose tissue structure. Knock-in mutant mice show encephalomyelopathy, impaired gait, mtDNA loss, altered mt dNTP pools and respiratory chain enzyme activities. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 60 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc10	C	A	17: 46,635,103 (GRCm39)	G300V	possibly damaging	Het
Adgrg7	C	G	16: 56,616,045 (GRCm39)		probably benign	Het
Agt	G	A	8: 125,290,842 (GRCm39)	T155M	probably benign	Het
Atp8b3	A	G	10: 80,361,633 (GRCm39)	V763A	probably benign	Het
Btn1a1	C	A	13: 23,648,420 (GRCm39)	V138L	probably benign	Het
Cd163	A	T	6: 124,305,924 (GRCm39)	N1109I	probably benign	Het
Cideb	T	A	14: 55,992,598 (GRCm39)	Q106L	possibly damaging	Het
Cntn1	A	G	15: 92,130,130 (GRCm39)	T126A	probably benign	Het
Dnai3	T	C	3: 145,802,982 (GRCm39)	K70E	probably damaging	Het
Elfn1	T	C	5: 139,957,226 (GRCm39)	Y77H	probably damaging	Het
Eml3	A	G	19: 8,912,358 (GRCm39)	H386R	probably damaging	Het
Fbxo21	A	G	5: 118,133,479 (GRCm39)	D413G	probably damaging	Het
Fkbp8	T	A	8: 70,984,413 (GRCm39)		probably null	Het
Fzd1	T	C	5: 4,807,336 (GRCm39)	Q82R	probably benign	Het
Gast	T	C	11: 100,227,394 (GRCm39)	L29P	probably benign	Het
Glb1l2	C	A	9: 26,717,713 (GRCm39)		probably benign	Het
Gm1110	C	G	9: 26,794,576 (GRCm39)	Q483H	probably benign	Het
Gm1110	T	A	9: 26,794,577 (GRCm39)	Q483L	probably benign	Het
Gpc6	T	C	14: 117,163,391 (GRCm39)	L15P	probably damaging	Het
Hagh	C	A	17: 25,076,536 (GRCm39)	S161*	probably null	Het
Hrh1	A	G	6: 114,457,814 (GRCm39)	D365G	probably benign	Het
Ighv1-36	A	T	12: 114,843,560 (GRCm39)	M100K	probably damaging	Het
Itgb8	A	T	12: 119,134,513 (GRCm39)	V518D	probably benign	Het
Krt82	T	C	15: 101,450,238 (GRCm39)	Y486C	probably damaging	Het
Lmbr1l	A	G	15: 98,810,357 (GRCm39)	S85P	probably damaging	Het
Met	A	G	6: 17,491,768 (GRCm39)	S177G	probably damaging	Het
Myl9	T	A	2: 156,623,048 (GRCm39)	I162N	possibly damaging	Het
Npat	T	A	9: 53,478,251 (GRCm39)	N973K	possibly damaging	Het
Or5p68	A	T	7: 107,945,889 (GRCm39)	C100S	probably damaging	Het
Pcdhga12	A	T	18: 37,901,190 (GRCm39)	D674V	possibly damaging	Het
Phtf1	T	A	3: 103,911,765 (GRCm39)	N702K	probably damaging	Het
Plaa	A	T	4: 94,457,714 (GRCm39)	I752N	probably damaging	Het
Pnpla2	T	C	7: 141,038,011 (GRCm39)	C194R	probably damaging	Het
Rnaseh2a	T	C	8: 85,691,776 (GRCm39)	N133S	probably benign	Het
Rps6ka1	T	A	4: 133,575,864 (GRCm39)	Q685L	probably benign	Het
Ryr1	C	A	7: 28,715,142 (GRCm39)	G4661C	unknown	Het
Samd13	T	A	3: 146,352,157 (GRCm39)	M65L	probably benign	Het
Sdr42e2	T	A	7: 120,430,403 (GRCm39)	V420E	possibly damaging	Het
Sec22c	A	G	9: 121,524,721 (GRCm39)	S21P	probably damaging	Het
Sh3d19	C	A	3: 86,014,329 (GRCm39)	T431K	probably benign	Het
Sin3b	A	G	8: 73,468,108 (GRCm39)	M277V	probably benign	Het
Sis	T	C	3: 72,854,834 (GRCm39)	T468A	possibly damaging	Het
Slitrk3	T	C	3: 72,956,513 (GRCm39)	N753S	probably benign	Het
Slitrk6	C	A	14: 110,989,478 (GRCm39)	L76F	probably damaging	Het
Stk3	C	T	15: 34,876,870 (GRCm39)	A478T	probably damaging	Het
Styxl2	A	T	1: 165,935,702 (GRCm39)	N165K	probably damaging	Het
Sugp1	C	A	8: 70,524,247 (GRCm39)	Y617*	probably null	Het
Tinag	T	C	9: 76,938,977 (GRCm39)	D167G	probably damaging	Het
Tmem209	A	T	6: 30,489,308 (GRCm39)	V514D	probably damaging	Het
Tmprss9	A	G	10: 80,723,320 (GRCm39)	H260R	probably benign	Het
Tnfrsf14	T	A	4: 155,011,112 (GRCm39)	Y83F	possibly damaging	Het
Tnfrsf8	A	T	4: 145,014,553 (GRCm39)	D285E	probably benign	Het
Togaram2	C	G	17: 72,004,873 (GRCm39)	A310G	probably benign	Het
Trpv3	A	G	11: 73,182,448 (GRCm39)	Y544C	probably damaging	Het
Ttl	T	A	2: 128,908,104 (GRCm39)	V13D	probably damaging	Het
Usp40	A	T	1: 87,908,694 (GRCm39)	D602E	probably benign	Het
Vamp5	A	G	6: 72,347,376 (GRCm39)		probably benign	Het
Vmn2r65	T	A	7: 84,589,402 (GRCm39)	H838L	possibly damaging	Het
Vps35l	T	A	7: 118,391,795 (GRCm39)	F493Y	probably benign	Het
Zfp960	T	A	17: 17,308,461 (GRCm39)	Y392N	probably benign	Het

Other mutations in Tk2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02447:Tk2	APN	8	104,967,770 (GRCm39)	missense	probably damaging	1.00
IGL02525:Tk2	APN	8	104,970,032 (GRCm39)	missense	probably benign	0.02
IGL03211:Tk2	APN	8	104,970,073 (GRCm39)	missense	probably damaging	1.00
R0333:Tk2	UTSW	8	104,975,146 (GRCm39)	unclassified	probably benign
R0691:Tk2	UTSW	8	104,957,824 (GRCm39)	missense	probably benign	0.16
R1851:Tk2	UTSW	8	104,975,077 (GRCm39)	nonsense	probably null
R3508:Tk2	UTSW	8	104,957,825 (GRCm39)	missense	probably benign	0.00
R3605:Tk2	UTSW	8	104,957,803 (GRCm39)	missense	possibly damaging	0.95
R4161:Tk2	UTSW	8	104,965,465 (GRCm39)	missense	probably benign	0.00
R5328:Tk2	UTSW	8	104,955,931 (GRCm39)	splice site	probably null
R5546:Tk2	UTSW	8	104,974,315 (GRCm39)	missense	possibly damaging	0.51
R6909:Tk2	UTSW	8	104,963,442 (GRCm39)	nonsense	probably null
R8098:Tk2	UTSW	8	104,957,804 (GRCm39)	missense	probably benign	0.05
R8354:Tk2	UTSW	8	104,967,746 (GRCm39)	critical splice donor site	probably null
R8357:Tk2	UTSW	8	104,963,450 (GRCm39)	missense	probably damaging	1.00
R8457:Tk2	UTSW	8	104,963,450 (GRCm39)	missense	probably damaging	1.00
R8978:Tk2	UTSW	8	104,957,809 (GRCm39)	missense	possibly damaging	0.78

Predicted Primers

PCR Primer
(F):5'- TGGAACCTTGGAGACACCTC -3'
(R):5'- TTTGCAGTCAGTCACAGGAAG -3'

Sequencing Primer
(F):5'- TTGGAGACACCTCACGGGAG -3'
(R):5'- CAGTCAGTCACAGGAAGGACTTC -3'

Posted On

2020-10-20