Incidental Mutation 'R1860:Timeless'
ID 203821
Institutional Source Beutler Lab
Gene Symbol Timeless
Ensembl Gene ENSMUSG00000039994
Gene Name timeless circadian clock 1
Synonyms tim
MMRRC Submission 039883-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1860 (G1)
Quality Score 225
Status Not validated
Chromosome 10
Chromosomal Location 128067934-128088810 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 128081983 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Lysine to Arginine at position 536 (K536R)
Ref Sequence ENSEMBL: ENSMUSP00000100879 (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: K536R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000058021
Gene: ENSMUSG00000039994
AA Change: K536R

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 noncoding transcript
Transcript: ENSMUST00000105240
Predicted Effect probably benign
Transcript: ENSMUST00000105242
AA Change: K536R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000100876
Gene: ENSMUSG00000039994
AA Change: K536R

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
SMART Domains Protein: ENSMUSP00000100877
Gene: ENSMUSG00000039994

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: K536R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000100878
Gene: ENSMUSG00000039994
AA Change: K536R

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: K536R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000100879
Gene: ENSMUSG00000039994
AA Change: K536R

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 noncoding transcript
Transcript: ENSMUST00000142484
Predicted Effect noncoding transcript
Transcript: ENSMUST00000145710
Predicted Effect noncoding transcript
Transcript: ENSMUST00000146945
Predicted Effect noncoding transcript
Transcript: ENSMUST00000142149
Predicted Effect noncoding transcript
Transcript: ENSMUST00000129147
Predicted Effect noncoding transcript
Transcript: ENSMUST00000135376
Predicted Effect noncoding transcript
Transcript: ENSMUST00000135538
Predicted Effect noncoding transcript
Transcript: ENSMUST00000136854
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: 97.4%
  • 3x: 96.8%
  • 10x: 95.1%
  • 20x: 91.7%
Validation Efficiency
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: 83 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930522L14Rik A G 5: 109,884,098 (GRCm39) C587R probably damaging Het
Abca16 T A 7: 120,133,986 (GRCm39) S1320T probably benign Het
Abra C A 15: 41,732,430 (GRCm39) R212L probably damaging Het
Acadsb T A 7: 131,045,958 (GRCm39) probably null Het
Adam26a A G 8: 44,022,578 (GRCm39) V304A possibly damaging Het
Adgre1 T C 17: 57,748,363 (GRCm39) V521A probably benign Het
Adh5 G A 3: 138,159,539 (GRCm39) V288I probably benign Het
Astn1 A C 1: 158,429,515 (GRCm39) N753T probably damaging Het
Atad2 A T 15: 57,960,114 (GRCm39) probably null Het
Best3 A G 10: 116,829,178 (GRCm39) T153A probably damaging Het
Ccdc122 G A 14: 77,348,847 (GRCm39) V226I probably damaging Het
Ccdc175 T C 12: 72,152,700 (GRCm39) Q735R probably benign Het
Cd19 T A 7: 126,008,813 (GRCm39) I499F probably damaging Het
Cftr T A 6: 18,268,288 (GRCm39) L749H probably benign Het
Clec2h G T 6: 128,652,790 (GRCm39) G186W probably damaging Het
Cpsf3 T A 12: 21,346,733 (GRCm39) I202N probably damaging Het
Crebbp G T 16: 3,905,600 (GRCm39) T1669N possibly damaging Het
Csmd3 A T 15: 47,522,588 (GRCm39) C2694S probably damaging Het
Cul4a G A 8: 13,173,565 (GRCm39) R204Q probably damaging Het
Derl2 A G 11: 70,909,169 (GRCm39) F43S probably damaging Het
Dnah14 T A 1: 181,591,525 (GRCm39) N3348K probably damaging Het
Dnhd1 T C 7: 105,353,412 (GRCm39) V2855A probably benign Het
Dpysl4 G T 7: 138,670,215 (GRCm39) C27F probably benign Het
Fam228b G A 12: 4,798,314 (GRCm39) A163V probably damaging Het
Fscn1 T C 5: 142,955,818 (GRCm39) probably null Het
Fzd5 C A 1: 64,774,153 (GRCm39) R536L probably damaging Het
Gm8180 T A 14: 44,021,196 (GRCm39) H4L probably benign Het
Gpr176 T A 2: 118,203,659 (GRCm39) N4Y probably damaging Het
Grin3a T C 4: 49,665,309 (GRCm39) I1109V possibly damaging Het
Hcar1 T A 5: 124,017,092 (GRCm39) I200F probably damaging Het
Heatr4 G A 12: 84,026,502 (GRCm39) Q252* probably null Het
Hps1 G A 19: 42,750,888 (GRCm39) H371Y probably damaging Het
Ikzf2 T C 1: 69,609,661 (GRCm39) T195A probably damaging Het
Kdm1b G A 13: 47,202,666 (GRCm39) A34T probably benign Het
Lef1 A G 3: 130,905,290 (GRCm39) N57S probably damaging Het
Ltn1 A T 16: 87,213,231 (GRCm39) D443E probably benign Het
Macroh2a1 A G 13: 56,231,017 (GRCm39) L287P probably damaging Het
Mamdc2 T C 19: 23,336,517 (GRCm39) T331A probably damaging Het
Marchf10 A T 11: 105,287,904 (GRCm39) S133T probably damaging Het
Mb A G 15: 76,901,784 (GRCm39) Y104H probably damaging Het
Mrc1 C A 2: 14,333,390 (GRCm39) P1357Q probably benign Het
Nfib C T 4: 82,241,917 (GRCm39) V425M probably damaging Het
Or12j2 G A 7: 139,916,132 (GRCm39) R119H possibly damaging Het
Or4a27 T G 2: 88,559,674 (GRCm39) I90L probably damaging Het
Or4b1b C A 2: 90,112,502 (GRCm39) C139F probably damaging Het
Or4c127 G A 2: 89,833,490 (GRCm39) V247I probably benign Het
Or4n4 A T 14: 50,518,848 (GRCm39) Y287* probably null Het
Or52u1 T C 7: 104,237,112 (GRCm39) S34P probably damaging Het
Or5b113 T A 19: 13,342,705 (GRCm39) S238T possibly damaging Het
Or5p53 A G 7: 107,533,597 (GRCm39) Y290C probably damaging Het
Or6c208 T C 10: 129,223,955 (GRCm39) F151S probably damaging Het
Or8b51 A T 9: 38,569,661 (GRCm39) V9E probably damaging Het
Phaf1 A G 8: 105,966,703 (GRCm39) E150G probably null Het
Piezo1 T C 8: 123,222,489 (GRCm39) N919S possibly damaging Het
Prkaca T C 8: 84,707,852 (GRCm39) S46P probably benign Het
Prkcb T G 7: 122,167,424 (GRCm39) V378G probably damaging Het
Ptprf A T 4: 118,081,129 (GRCm39) L576Q probably damaging Het
Rapgef4 T C 2: 72,065,064 (GRCm39) V687A probably benign Het
Rsad2 C T 12: 26,500,616 (GRCm39) V224I probably damaging Het
Ryr1 A T 7: 28,708,977 (GRCm39) D4796E unknown Het
Scn1a C T 2: 66,148,326 (GRCm39) S1073N probably damaging Het
Slc26a3 A G 12: 31,515,845 (GRCm39) M582V probably benign Het
Tbc1d32 A T 10: 55,999,633 (GRCm39) Y846* probably null Het
Tbk1 A T 10: 121,383,076 (GRCm39) M719K probably benign Het
Tle6 G T 10: 81,430,163 (GRCm39) Q330K probably damaging Het
Tmem208 A G 8: 106,061,438 (GRCm39) K155E possibly damaging Het
Toe1 T C 4: 116,662,426 (GRCm39) Y273C probably damaging Het
Tppp2 A C 14: 52,158,062 (GRCm39) N169T probably benign Het
Ttll6 T A 11: 96,029,700 (GRCm39) Y204* probably null Het
Ubxn11 G A 4: 133,852,149 (GRCm39) S32N probably damaging Het
Usp8 G A 2: 126,597,960 (GRCm39) C961Y probably damaging Het
Vdac3 A T 8: 23,070,515 (GRCm39) I132K possibly damaging Het
Vmn2r124 G T 17: 18,269,759 (GRCm39) W5L probably benign Het
Vmn2r71 A T 7: 85,264,782 (GRCm39) D38V probably damaging Het
Vmn2r87 C T 10: 130,315,755 (GRCm39) V104I probably benign Het
Vmn2r97 C T 17: 19,167,648 (GRCm39) T634I probably benign Het
Vps50 T C 6: 3,520,279 (GRCm39) probably null Het
Wwc2 T C 8: 48,443,137 (GRCm39) N32S possibly damaging Het
Ythdc2 T A 18: 45,006,023 (GRCm39) I1172K possibly damaging Het
Zfp14 C T 7: 29,738,116 (GRCm39) V290M probably damaging Het
Zfp317 G A 9: 19,553,280 (GRCm39) A18T possibly damaging Het
Zfp354b A T 11: 50,814,369 (GRCm39) N185K probably benign Het
Zscan21 T A 5: 138,124,892 (GRCm39) D269E probably benign 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
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
R7213:Timeless UTSW 10 128,079,158 (GRCm39) missense probably benign
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'- GTAATGGCATCTTCCCCTGAC -3'
(R):5'- ACAGACATAGCCATGGGAGC -3'

Sequencing Primer
(F):5'- GGAAATATACAGTGCCCATTGCTGC -3'
(R):5'- CATAGCCATGGGAGCAGGGTG -3'
Posted On 2014-06-23