Incidental Mutation 'R3508:Tk2'
ID 267467
Institutional Source Beutler Lab
Gene Symbol Tk2
Ensembl Gene ENSMUSG00000035824
Gene Name thymidine kinase 2, mitochondrial
Synonyms
MMRRC Submission 040664-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.755) question?
Stock # R3508 (G1)
Quality Score 225
Status Not validated
Chromosome 8
Chromosomal Location 104953317-104975190 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 104957825 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Isoleucine at position 174 (V174I)
Ref Sequence ENSEMBL: ENSMUSP00000148642 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000050211] [ENSMUST00000211995] [ENSMUST00000212209] [ENSMUST00000212275]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000050211
AA Change: V174I

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000053616
Gene: ENSMUSG00000035824
AA Change: V174I

DomainStartEndE-ValueType
low complexity region 2 35 N/A INTRINSIC
Pfam:dNK 58 267 1.2e-67 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000211995
Predicted Effect noncoding transcript
Transcript: ENSMUST00000212165
Predicted Effect probably benign
Transcript: ENSMUST00000212209
Predicted Effect probably benign
Transcript: ENSMUST00000212275
AA Change: V174I

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000212805
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.0%
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: 62 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca8a A T 11: 109,953,991 (GRCm39) F816L probably benign Het
Adgrl3 C A 5: 81,872,103 (GRCm39) N932K probably damaging Het
Apol8 T C 15: 77,633,643 (GRCm39) E311G probably damaging Het
Atad2b G A 12: 5,000,595 (GRCm39) probably null Het
Carmil1 A G 13: 24,203,659 (GRCm39) probably benign Het
Cdc20b T C 13: 113,217,576 (GRCm39) S332P possibly damaging Het
Cep162 A G 9: 87,114,030 (GRCm39) probably null Het
Cfap54 T A 10: 92,721,286 (GRCm39) S2482C unknown Het
Cnpy1 T C 5: 28,412,365 (GRCm39) E107G probably damaging Het
Crtac1 C T 19: 42,293,180 (GRCm39) V310I probably benign Het
Csmd3 CCTTTGCGCTT CCTT 15: 47,604,632 (GRCm39) probably null Het
Elmo1 T C 13: 20,789,402 (GRCm39) I706T probably damaging Het
F12 T C 13: 55,568,872 (GRCm39) T297A probably benign Het
Fanci A G 7: 79,083,220 (GRCm39) I736V probably benign Het
Fbn1 T C 2: 125,148,247 (GRCm39) N2667S probably benign Het
Flt4 T C 11: 49,524,941 (GRCm39) S596P probably damaging Het
Fndc1 G A 17: 7,983,940 (GRCm39) R1329* probably null Het
Gjd4 G T 18: 9,280,811 (GRCm39) S89* probably null Het
H2-M10.1 T G 17: 36,636,506 (GRCm39) R99S possibly damaging Het
Homer3 T A 8: 70,744,005 (GRCm39) V243D probably benign Het
Hspa14 A G 2: 3,492,045 (GRCm39) S437P probably damaging Het
Inpp1 A T 1: 52,838,550 (GRCm39) I33N probably damaging Het
Ipo5 T A 14: 121,176,956 (GRCm39) Y714N probably damaging Het
Kif27 T C 13: 58,461,026 (GRCm39) E898G possibly damaging Het
Klhdc7b T A 15: 89,271,095 (GRCm39) M1K probably null Het
Krt87 A G 15: 101,386,039 (GRCm39) Y241H probably benign Het
Mfsd4b1 A G 10: 39,878,715 (GRCm39) I394T probably benign Het
Micall1 A G 15: 79,006,965 (GRCm39) D264G probably damaging Het
Mms22l T G 4: 24,586,224 (GRCm39) D905E probably benign Het
Musk A G 4: 58,327,347 (GRCm39) D217G probably damaging Het
Napb T C 2: 148,540,880 (GRCm39) T236A probably benign Het
Nbn T A 4: 15,962,387 (GRCm39) D38E probably damaging Het
Ncaph T C 2: 126,969,113 (GRCm39) N87D probably benign Het
Or4a78 A G 2: 89,497,816 (GRCm39) V138A probably benign Het
Pcdhb13 T A 18: 37,576,204 (GRCm39) V194E probably damaging Het
Pck1 T C 2: 173,000,177 (GRCm39) V536A possibly damaging Het
Pld5 C T 1: 175,821,603 (GRCm39) G188S probably damaging Het
Plekha8 T C 6: 54,590,179 (GRCm39) V48A probably damaging Het
Pnkd A G 1: 74,389,793 (GRCm39) T306A probably benign Het
Ppm1k T C 6: 57,491,975 (GRCm39) E279G probably damaging Het
Ppm1l G T 3: 69,456,813 (GRCm39) K243N possibly damaging Het
Ppp1r13b T C 12: 111,838,801 (GRCm39) T26A probably damaging Het
Rtel1 T C 2: 180,964,202 (GRCm39) V67A probably benign Het
Rxfp4 T C 3: 88,559,899 (GRCm39) E184G probably damaging Het
Scp2d1 A G 2: 144,665,918 (GRCm39) I86V probably benign Het
Sec16a G T 2: 26,315,862 (GRCm39) P1718Q probably damaging Het
Sgcg T A 14: 61,459,195 (GRCm39) T245S probably benign Het
Slc18a2 A G 19: 59,261,989 (GRCm39) T215A probably benign Het
Sorcs1 G A 19: 50,213,613 (GRCm39) R705C probably damaging Het
Sox17 G T 1: 4,562,378 (GRCm39) P146Q probably damaging Het
Spata31d1e A T 13: 59,890,319 (GRCm39) Y500* probably null Het
Stimate C T 14: 30,594,537 (GRCm39) L217F probably damaging Het
Sybu T A 15: 44,536,478 (GRCm39) E616V probably damaging Het
Tmc5 G A 7: 118,244,618 (GRCm39) V499I probably benign Het
Tonsl T C 15: 76,523,956 (GRCm39) T15A probably benign Het
Ttll12 A G 15: 83,464,831 (GRCm39) I448T probably damaging Het
Ttn A G 2: 76,584,101 (GRCm39) S22336P probably damaging Het
Ubap1 C A 4: 41,379,163 (GRCm39) H126N probably damaging Het
Upf1 C T 8: 70,791,110 (GRCm39) R544H probably damaging Het
Vmn2r84 T C 10: 130,226,777 (GRCm39) N354D probably damaging Het
Vpreb3 A C 10: 75,785,037 (GRCm39) H45P probably benign Het
Zc3h13 T A 14: 75,546,380 (GRCm39) Y160* probably null Het
Other mutations in Tk2
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R8454:Tk2 UTSW 8 104,967,746 (GRCm39) critical splice donor site probably null
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'- AACCAAGGCCAGAGTTCCTTC -3'
(R):5'- GTGGACCACACTATGCAACATG -3'

Sequencing Primer
(F):5'- AAGGCCAGAGTTCCTTCATGGAC -3'
(R):5'- ACACTATGCAACATGCTCTTGGTG -3'
Posted On 2015-02-18