Incidental Mutation 'R7213:Timeless'
ID 561228
Institutional Source Beutler Lab
Gene Symbol Timeless
Ensembl Gene ENSMUSG00000039994
Gene Name timeless circadian clock 1
Synonyms tim
MMRRC Submission 045341-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7213 (G1)
Quality Score 225.009
Status Validated
Chromosome 10
Chromosomal Location 128067934-128088810 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 128079158 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 335 (V335A)
Ref Sequence ENSEMBL: ENSMUSP00000058021 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000055539] [ENSMUST00000105242] [ENSMUST00000105243] [ENSMUST00000105244] [ENSMUST00000105245] [ENSMUST00000125289]
AlphaFold Q9R1X4
Predicted Effect probably benign
Transcript: ENSMUST00000055539
AA Change: V335A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000058021
Gene: ENSMUSG00000039994
AA Change: V335A

DomainStartEndE-ValueType
Pfam:TIMELESS 21 285 2.2e-102 PFAM
low complexity region 381 395 N/A INTRINSIC
low complexity region 528 537 N/A INTRINSIC
low complexity region 653 682 N/A INTRINSIC
Pfam:TIMELESS_C 722 1197 1.9e-186 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000105242
AA Change: V335A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000100876
Gene: ENSMUSG00000039994
AA Change: V335A

DomainStartEndE-ValueType
Pfam:TIMELESS 21 285 2.1e-102 PFAM
low complexity region 381 395 N/A INTRINSIC
low complexity region 528 537 N/A INTRINSIC
low complexity region 653 682 N/A INTRINSIC
Pfam:TIMELESS_C 722 1196 4.4e-187 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000105243
AA Change: V335A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000100877
Gene: ENSMUSG00000039994
AA Change: V335A

DomainStartEndE-ValueType
Pfam:TIMELESS 21 285 7.8e-104 PFAM
low complexity region 381 395 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000105244
AA Change: V335A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000100878
Gene: ENSMUSG00000039994
AA Change: V335A

DomainStartEndE-ValueType
Pfam:TIMELESS 21 285 2.3e-103 PFAM
low complexity region 381 395 N/A INTRINSIC
low complexity region 528 537 N/A INTRINSIC
low complexity region 653 682 N/A INTRINSIC
Pfam:TIMELESS_C 722 1196 5e-187 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000105245
AA Change: V335A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000100879
Gene: ENSMUSG00000039994
AA Change: V335A

DomainStartEndE-ValueType
Pfam:TIMELESS 24 284 1.1e-81 PFAM
low complexity region 381 395 N/A INTRINSIC
low complexity region 528 537 N/A INTRINSIC
low complexity region 653 682 N/A INTRINSIC
Pfam:TIMELESS_C 722 1197 1.9e-186 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000125289
SMART Domains Protein: ENSMUSP00000132079
Gene: ENSMUSG00000039994

DomainStartEndE-ValueType
Pfam:TIMELESS 1 123 3.6e-47 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency 99% (80/81)
MGI Phenotype FUNCTION: The protein encoded by this gene is highly conserved and is involved in cell survival after damage or stress, increase in DNA polymerase epsilon activity, maintenance of telomere length, and epithelial cell morphogenesis. The encoded protein also plays a role in the circadian rhythm autoregulatory loop, interacting with the PERIOD genes (PER1, PER2, and PER3) and others to downregulate activation of PER1 by CLOCK/ARNTL. Changes in this gene or its expression may promote prostate cancer, lung cancer, breast cancer, and mental disorders. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]
PHENOTYPE: Mice homozygous for a targeted mutation exhibit early embryonic lethality at aprroximately the time of implantation. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 80 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2010315B03Rik G T 9: 124,056,530 (GRCm39) Y131* probably null Het
2310009B15Rik A T 1: 138,781,367 (GRCm39) V94D probably damaging Het
Actr1b T A 1: 36,741,221 (GRCm39) N120I probably damaging Het
Adam17 A T 12: 21,386,679 (GRCm39) Y452* probably null Het
Adam19 A T 11: 46,012,298 (GRCm39) T265S probably benign Het
Adgrb1 A G 15: 74,441,733 (GRCm39) T945A probably benign Het
Bpifa5 G A 2: 154,007,903 (GRCm39) V182M possibly damaging Het
Celsr3 C T 9: 108,726,239 (GRCm39) T3156I probably damaging Het
Cntrl A G 2: 35,025,692 (GRCm39) M674V possibly damaging Het
Cry2 C T 2: 92,244,004 (GRCm39) V390I probably benign Het
Cspg4b T A 13: 113,454,475 (GRCm39) F174I Het
Cwc25 G T 11: 97,644,855 (GRCm39) Q168K probably benign Het
Dcbld2 C T 16: 58,271,126 (GRCm39) A301V probably benign Het
Dclre1a T C 19: 56,518,067 (GRCm39) Y1004C probably damaging Het
Ddhd1 A C 14: 45,895,210 (GRCm39) S87A probably benign Het
Ear1 A G 14: 44,056,611 (GRCm39) C86R probably damaging Het
Epha5 T C 5: 84,381,782 (GRCm39) probably null Het
Fat2 A T 11: 55,171,871 (GRCm39) Y2947* probably null Het
Fat4 G A 3: 39,053,236 (GRCm39) V4077M possibly damaging Het
Fbxl12 A T 9: 20,550,304 (GRCm39) V140E probably damaging Het
Fbxo16 A G 14: 65,536,868 (GRCm39) probably null Het
Fto A T 8: 92,118,135 (GRCm39) Q29L probably benign Het
Gk5 C T 9: 96,027,765 (GRCm39) T200M probably damaging Het
Gm5916 C T 9: 36,039,946 (GRCm39) G14E possibly damaging Het
Gm9972 A T 11: 42,927,235 (GRCm39) probably benign Het
Gpr139 T A 7: 118,744,322 (GRCm39) M88L probably benign Het
Gpr26 T C 7: 131,569,219 (GRCm39) L188P probably damaging Het
H2ac4 G T 13: 23,935,146 (GRCm39) A11S unknown Het
Hbp1 A T 12: 31,987,196 (GRCm39) S219T probably benign Het
Hr A T 14: 70,795,790 (GRCm39) E445V probably damaging Het
Il12rb1 A G 8: 71,269,097 (GRCm39) K426E probably benign Het
Itgbl1 G A 14: 124,210,709 (GRCm39) C469Y probably damaging Het
Kdm2b A T 5: 123,059,532 (GRCm39) N523K probably damaging Het
Kptn A G 7: 15,854,704 (GRCm39) N125S possibly damaging Het
Krt17 T C 11: 100,149,356 (GRCm39) N238S probably benign Het
Lemd3 G A 10: 120,814,145 (GRCm39) R363* probably null Het
Mmrn1 G A 6: 60,921,527 (GRCm39) probably benign Het
Mtus1 T C 8: 41,537,524 (GRCm39) D64G probably damaging Het
Muc16 A G 9: 18,552,712 (GRCm39) V4527A probably benign Het
Naip2 T A 13: 100,323,991 (GRCm39) D193V probably damaging Het
Nbeal1 G C 1: 60,276,310 (GRCm39) V684L probably benign Het
Nf1 A G 11: 79,360,645 (GRCm39) H1462R probably benign Het
Or2n1b T C 17: 38,459,965 (GRCm39) V162A probably benign Het
Or5ak20 A T 2: 85,183,900 (GRCm39) Y123* probably null Het
Pappa2 T A 1: 158,764,456 (GRCm39) T352S possibly damaging Het
Pcnt A G 10: 76,244,738 (GRCm39) L1114P probably damaging Het
Pde6b T C 5: 108,551,956 (GRCm39) Y212H probably damaging Het
Pik3c2g A T 6: 139,805,990 (GRCm39) I604F Het
Pld2 A G 11: 70,444,198 (GRCm39) D498G probably benign Het
Prag1 A T 8: 36,613,769 (GRCm39) Q1107L probably damaging Het
Pwp1 A T 10: 85,712,173 (GRCm39) I110F probably benign Het
Rims4 C T 2: 163,705,981 (GRCm39) V218I probably benign Het
Rnf10 C T 5: 115,380,532 (GRCm39) S754N probably damaging Het
Rnf10 T C 5: 115,380,533 (GRCm39) S754G probably damaging Het
Sel1l2 A T 2: 140,086,055 (GRCm39) V512E probably damaging Het
Shank2 T A 7: 143,585,146 (GRCm39) M49K probably benign Het
Sipa1 T C 19: 5,710,551 (GRCm39) D153G probably damaging Het
Slc46a2 C T 4: 59,914,279 (GRCm39) V215I possibly damaging Het
Slco6c1 G A 1: 97,055,671 (GRCm39) L77F probably benign Het
Smarca2 T C 19: 26,624,531 (GRCm39) L397P possibly damaging Het
Spg7 C T 8: 123,816,971 (GRCm39) A554V probably damaging Het
Stab1 T A 14: 30,865,630 (GRCm39) M1753L probably benign Het
Stk11 A G 10: 79,952,452 (GRCm39) M1V probably null Het
Supt6 C A 11: 78,122,976 (GRCm39) G136C probably damaging Het
Svil G T 18: 5,094,574 (GRCm39) R1418L probably damaging Het
Tfg A G 16: 56,521,516 (GRCm39) S167P probably benign Het
Tll2 C A 19: 41,108,666 (GRCm39) R328L probably damaging Het
Tomm7 T C 5: 24,049,059 (GRCm39) S5G possibly damaging Het
Ttc39c G A 18: 12,820,138 (GRCm39) probably null Het
Ttn T C 2: 76,556,105 (GRCm39) E30300G probably benign Het
Tuba4a A T 1: 75,192,341 (GRCm39) D452E possibly damaging Het
Tubgcp2 T C 7: 139,587,927 (GRCm39) I233V probably benign Het
Tubgcp5 T A 7: 55,455,860 (GRCm39) V296E probably damaging Het
Vmn2r53 T C 7: 12,334,983 (GRCm39) S226G probably benign Het
Xrcc6 T C 15: 81,901,027 (GRCm39) probably benign Het
Zfhx4 C A 3: 5,461,704 (GRCm39) D1192E probably benign Het
Zfp180 G T 7: 23,803,938 (GRCm39) W119L possibly damaging Het
Zfp3 A G 11: 70,663,351 (GRCm39) I437V probably benign Het
Zfp616 A T 11: 73,976,689 (GRCm39) Q986L probably benign Het
Zfp937 T A 2: 150,081,385 (GRCm39) C472S probably damaging Het
Other mutations in Timeless
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00091:Timeless APN 10 128,077,577 (GRCm39) missense probably damaging 1.00
IGL02157:Timeless APN 10 128,078,255 (GRCm39) missense probably benign 0.01
IGL02300:Timeless APN 10 128,080,676 (GRCm39) missense probably benign 0.00
IGL02587:Timeless APN 10 128,075,785 (GRCm39) missense probably damaging 0.99
IGL02588:Timeless APN 10 128,079,203 (GRCm39) missense probably damaging 1.00
IGL02892:Timeless APN 10 128,080,120 (GRCm39) missense probably damaging 1.00
IGL02930:Timeless APN 10 128,083,060 (GRCm39) missense probably benign 0.00
IGL02986:Timeless APN 10 128,085,629 (GRCm39) missense possibly damaging 0.82
IGL03345:Timeless APN 10 128,083,455 (GRCm39) missense probably benign 0.04
IGL03393:Timeless APN 10 128,087,924 (GRCm39) missense probably damaging 1.00
R0388:Timeless UTSW 10 128,077,294 (GRCm39) splice site probably null
R0607:Timeless UTSW 10 128,082,203 (GRCm39) missense probably benign
R0638:Timeless UTSW 10 128,080,542 (GRCm39) nonsense probably null
R0734:Timeless UTSW 10 128,085,929 (GRCm39) missense probably damaging 1.00
R1346:Timeless UTSW 10 128,078,234 (GRCm39) missense possibly damaging 0.83
R1625:Timeless UTSW 10 128,076,493 (GRCm39) missense probably damaging 0.99
R1771:Timeless UTSW 10 128,083,477 (GRCm39) missense probably benign 0.11
R1860:Timeless UTSW 10 128,081,983 (GRCm39) missense probably benign 0.00
R1920:Timeless UTSW 10 128,077,583 (GRCm39) missense probably damaging 1.00
R1988:Timeless UTSW 10 128,080,056 (GRCm39) missense probably damaging 0.98
R2981:Timeless UTSW 10 128,084,327 (GRCm39) missense probably benign 0.34
R4359:Timeless UTSW 10 128,083,211 (GRCm39) missense probably benign 0.00
R4647:Timeless UTSW 10 128,075,825 (GRCm39) missense possibly damaging 0.80
R4753:Timeless UTSW 10 128,075,889 (GRCm39) utr 5 prime probably benign
R4868:Timeless UTSW 10 128,083,230 (GRCm39) missense probably benign
R4901:Timeless UTSW 10 128,086,631 (GRCm39) missense probably damaging 1.00
R4956:Timeless UTSW 10 128,077,520 (GRCm39) missense probably damaging 1.00
R5341:Timeless UTSW 10 128,083,047 (GRCm39) missense possibly damaging 0.81
R5439:Timeless UTSW 10 128,077,604 (GRCm39) missense probably damaging 1.00
R5585:Timeless UTSW 10 128,076,112 (GRCm39) missense probably damaging 0.97
R5842:Timeless UTSW 10 128,083,328 (GRCm39) critical splice donor site probably null
R5843:Timeless UTSW 10 128,080,113 (GRCm39) splice site probably null
R6005:Timeless UTSW 10 128,080,069 (GRCm39) missense probably damaging 0.99
R6271:Timeless UTSW 10 128,086,593 (GRCm39) missense probably damaging 1.00
R6558:Timeless UTSW 10 128,085,432 (GRCm39) missense probably benign 0.01
R6694:Timeless UTSW 10 128,075,868 (GRCm39) critical splice donor site probably null
R6738:Timeless UTSW 10 128,076,504 (GRCm39) missense probably damaging 1.00
R6760:Timeless UTSW 10 128,081,986 (GRCm39) missense probably benign 0.38
R7248:Timeless UTSW 10 128,087,870 (GRCm39) missense probably benign
R7345:Timeless UTSW 10 128,085,623 (GRCm39) missense probably damaging 1.00
R7463:Timeless UTSW 10 128,086,295 (GRCm39) missense probably benign 0.00
R7513:Timeless UTSW 10 128,085,399 (GRCm39) missense probably damaging 0.99
R7574:Timeless UTSW 10 128,080,538 (GRCm39) missense probably damaging 1.00
R8220:Timeless UTSW 10 128,082,265 (GRCm39) missense probably damaging 0.98
R8418:Timeless UTSW 10 128,086,605 (GRCm39) missense probably benign 0.02
R8742:Timeless UTSW 10 128,083,107 (GRCm39) missense probably benign 0.00
R8765:Timeless UTSW 10 128,080,412 (GRCm39) critical splice donor site probably null
R9508:Timeless UTSW 10 128,076,096 (GRCm39) missense probably benign 0.01
X0028:Timeless UTSW 10 128,086,194 (GRCm39) missense probably benign 0.01
Predicted Primers PCR Primer
(F):5'- ACAAATGTCCTCCTAGGTGTC -3'
(R):5'- ATCTCCATTCTGTCTGGGGC -3'

Sequencing Primer
(F):5'- GGTGTCTTTTTCAAGAAAATTCTGG -3'
(R):5'- CGAGGTCAGCTTTCCCTTGG -3'
Posted On 2019-06-26