Incidental Mutation 'R1920:Timeless'
ID 212964
Institutional Source Beutler Lab
Gene Symbol Timeless
Ensembl Gene ENSMUSG00000039994
Gene Name timeless circadian clock 1
Synonyms tim
MMRRC Submission 039938-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1920 (G1)
Quality Score 225
Status Validated
Chromosome 10
Chromosomal Location 128067934-128088810 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 128077583 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Threonine at position 221 (I221T)
Ref Sequence ENSEMBL: ENSMUSP00000100879 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000055539] [ENSMUST00000105242] [ENSMUST00000105243] [ENSMUST00000105244] [ENSMUST00000105245] [ENSMUST00000125289]
AlphaFold Q9R1X4
Predicted Effect probably damaging
Transcript: ENSMUST00000055539
AA Change: I221T

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000058021
Gene: ENSMUSG00000039994
AA Change: I221T

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 damaging
Transcript: ENSMUST00000105242
AA Change: I221T

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000100876
Gene: ENSMUSG00000039994
AA Change: I221T

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 damaging
Transcript: ENSMUST00000105243
AA Change: I221T

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000100877
Gene: ENSMUSG00000039994
AA Change: I221T

DomainStartEndE-ValueType
Pfam:TIMELESS 21 285 7.8e-104 PFAM
low complexity region 381 395 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000105244
AA Change: I221T

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000100878
Gene: ENSMUSG00000039994
AA Change: I221T

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 damaging
Transcript: ENSMUST00000105245
AA Change: I221T

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000100879
Gene: ENSMUSG00000039994
AA Change: I221T

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
Predicted Effect noncoding transcript
Transcript: ENSMUST00000135538
Predicted Effect noncoding transcript
Transcript: ENSMUST00000142149
Predicted Effect noncoding transcript
Transcript: ENSMUST00000146945
Predicted Effect noncoding transcript
Transcript: ENSMUST00000145710
Predicted Effect noncoding transcript
Transcript: ENSMUST00000135376
Meta Mutation Damage Score 0.5334 question?
Coding Region Coverage
  • 1x: 97.5%
  • 3x: 97.0%
  • 10x: 95.7%
  • 20x: 93.4%
Validation Efficiency 98% (101/103)
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: 98 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700056E22Rik A G 1: 183,765,828 (GRCm39) V77A probably benign Het
Actl7a G A 4: 56,744,135 (GRCm39) V221M probably damaging Het
Alkbh2 C T 5: 114,262,287 (GRCm39) E148K probably damaging Het
Arhgef10 C T 8: 15,006,987 (GRCm39) probably benign Het
Asgr2 T C 11: 69,989,123 (GRCm39) L86P possibly damaging Het
Atp12a A G 14: 56,624,308 (GRCm39) R919G probably benign Het
Atrn A G 2: 130,836,971 (GRCm39) Y1145C probably damaging Het
B3gnt5 T G 16: 19,588,294 (GRCm39) L171R probably benign Het
Bbof1 T A 12: 84,457,859 (GRCm39) N41K possibly damaging Het
Bdp1 A T 13: 100,235,097 (GRCm39) W166R probably benign Het
Bean1 A T 8: 104,937,742 (GRCm39) H107L possibly damaging Het
Brd4 T C 17: 32,417,060 (GRCm39) probably benign Het
Cadps T C 14: 12,465,859 (GRCm38) K1017R possibly damaging Het
Cep78 G A 19: 15,951,715 (GRCm39) probably benign Het
Cfap70 C T 14: 20,445,020 (GRCm39) A1087T probably damaging Het
Cideb A G 14: 55,992,700 (GRCm39) V72A probably benign Het
Cpz T C 5: 35,675,012 (GRCm39) E79G probably damaging Het
Crybg1 A G 10: 43,873,544 (GRCm39) L1188P probably damaging Het
Cuzd1 G A 7: 130,911,425 (GRCm39) P518L probably benign Het
Cyp2j5 A T 4: 96,551,491 (GRCm39) N77K probably damaging Het
Cyp4f39 T G 17: 32,702,265 (GRCm39) F254C probably benign Het
Dkk1 C A 19: 30,524,731 (GRCm39) V225L probably damaging Het
Dlg5 T C 14: 24,226,639 (GRCm39) Y421C probably damaging Het
Dll3 T C 7: 27,998,348 (GRCm39) T206A probably benign Het
Dnhd1 T C 7: 105,362,614 (GRCm39) C3766R probably benign Het
Dock9 G T 14: 121,820,792 (GRCm39) S1534Y probably damaging Het
Dst T C 1: 34,200,110 (GRCm39) V96A probably damaging Het
F2r A G 13: 95,740,698 (GRCm39) F279S probably damaging Het
Farp1 C A 14: 121,492,908 (GRCm39) N503K probably benign Het
Fbxw2 G A 2: 34,712,776 (GRCm39) T95I probably damaging Het
Fis1 A G 5: 136,994,461 (GRCm39) T50A probably benign Het
Frzb T G 2: 80,276,772 (GRCm39) E138A probably damaging Het
Fsip2 A T 2: 82,817,164 (GRCm39) D4299V probably benign Het
Fyco1 C T 9: 123,659,478 (GRCm39) D233N probably damaging Het
Gmpr A G 13: 45,667,997 (GRCm39) probably benign Het
Hc C T 2: 34,919,407 (GRCm39) probably benign Het
Hnrnpa1 T C 15: 103,150,699 (GRCm39) M186T possibly damaging Het
Kl A G 5: 150,906,132 (GRCm39) K501E probably benign Het
Klhl42 A G 6: 147,009,427 (GRCm39) N422S probably damaging Het
Kmt2d C G 15: 98,753,471 (GRCm39) K127N probably damaging Het
Kmt2d T A 15: 98,753,472 (GRCm39) K127M probably damaging Het
Krt39 T A 11: 99,405,461 (GRCm39) T480S probably benign Het
Lims2 T A 18: 32,088,395 (GRCm39) C198* probably null Het
Mctp1 A G 13: 76,532,729 (GRCm39) N26D possibly damaging Het
Mdm4 A G 1: 132,931,538 (GRCm39) S168P probably benign Het
Myo3a A G 2: 22,455,008 (GRCm39) Y71C probably benign Het
Nlrp9c T A 7: 26,084,319 (GRCm39) D420V probably damaging Het
Ntf3 A T 6: 126,079,485 (GRCm39) I7N possibly damaging Het
Or10ag52 G A 2: 87,043,721 (GRCm39) G162S probably benign Het
Or13c25 G T 4: 52,910,849 (GRCm39) T315K probably benign Het
Or4c119 A G 2: 88,986,925 (GRCm39) V198A probably benign Het
Or8b38 T C 9: 37,972,981 (GRCm39) Y122H probably damaging Het
Papln C A 12: 83,836,028 (GRCm39) Y1222* probably null Het
Pgm3 T G 9: 86,440,531 (GRCm39) I387L possibly damaging Het
Pira12 G C 7: 3,900,871 (GRCm39) P20R probably damaging Het
Pkd1 C A 17: 24,814,131 (GRCm39) P4167Q probably damaging Het
Plcb4 T A 2: 135,854,947 (GRCm39) V1174E probably damaging Het
Polr1b A G 2: 128,943,031 (GRCm39) N9D probably benign Het
Prkaa2 G A 4: 104,893,950 (GRCm39) Q456* probably null Het
Ptch2 G T 4: 116,965,858 (GRCm39) V425L probably benign Het
Ptprh A T 7: 4,552,394 (GRCm39) S957T probably benign Het
Riok1 A G 13: 38,241,177 (GRCm39) D444G probably benign Het
Rrbp1 A T 2: 143,830,211 (GRCm39) V652E probably benign Het
Rrp36 C T 17: 46,983,671 (GRCm39) R47Q possibly damaging Het
Sec24c T C 14: 20,736,955 (GRCm39) S304P probably damaging Het
Serpinb6b A T 13: 33,158,991 (GRCm39) D64V possibly damaging Het
Serpinb9b A T 13: 33,223,531 (GRCm39) probably null Het
Six6 T A 12: 72,988,538 (GRCm39) I237N probably damaging Het
Slc25a36 A T 9: 96,975,135 (GRCm39) M127K probably benign Het
Slc2a10 A G 2: 165,356,550 (GRCm39) D70G probably damaging Het
Slc2a3 T A 6: 122,713,700 (GRCm39) I171F probably damaging Het
Smc4 A G 3: 68,940,401 (GRCm39) T1087A probably damaging Het
Spg21 A G 9: 65,391,779 (GRCm39) Y242C probably damaging Het
St14 A G 9: 31,001,166 (GRCm39) V855A possibly damaging Het
Stx2 G A 5: 129,065,903 (GRCm39) T251M probably damaging Het
Svs3b A T 2: 164,097,848 (GRCm39) S158T probably benign Het
Synpo C T 18: 60,736,661 (GRCm39) M428I probably benign Het
Tasor2 A T 13: 3,626,612 (GRCm39) Y1113N possibly damaging Het
Tbc1d31 G A 15: 57,775,760 (GRCm39) R17H probably damaging Het
Tbl3 G A 17: 24,923,477 (GRCm39) T284I probably benign Het
Tcof1 T C 18: 60,971,927 (GRCm39) T127A possibly damaging Het
Tgoln1 T C 6: 72,593,084 (GRCm39) E132G probably benign Het
Tmem176b C T 6: 48,815,138 (GRCm39) A52T possibly damaging Het
Tmem192 C T 8: 65,418,235 (GRCm39) L207F probably damaging Het
Trank1 T C 9: 111,176,996 (GRCm39) probably null Het
Ttc7b C T 12: 100,381,389 (GRCm39) probably null Het
Tubb5 T C 17: 36,146,190 (GRCm39) Y340C probably benign Het
Ubr1 G A 2: 120,761,449 (GRCm39) T576I probably benign Het
Vcan T C 13: 89,841,134 (GRCm39) E1470G probably damaging Het
Vmn1r200 T A 13: 22,579,663 (GRCm39) N146K probably damaging Het
Vmn2r120 T A 17: 57,831,839 (GRCm39) I317F probably benign Het
Vmn2r61 T C 7: 41,949,710 (GRCm39) I710T possibly damaging Het
Wipf1 T A 2: 73,270,499 (GRCm39) K61N probably benign Het
Zfp112 T C 7: 23,824,662 (GRCm39) V210A probably benign Het
Zfp612 G A 8: 110,815,095 (GRCm39) V101M probably benign Het
Zfp637 A G 6: 117,822,681 (GRCm39) R270G probably damaging Het
Zfp652 A G 11: 95,654,851 (GRCm39) E418G possibly damaging Het
Zfp97 A G 17: 17,365,265 (GRCm39) I255V 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
R1860:Timeless UTSW 10 128,081,983 (GRCm39) missense probably benign 0.00
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'- AGCCTTAGCCACAGAGTGAG -3'
(R):5'- GAGCTATTCATGGGCCTTGG -3'

Sequencing Primer
(F):5'- TTAGCCACAGAGTGAGCTGCTG -3'
(R):5'- TTCATGGGCCTTGGATAGAACAC -3'
Posted On 2014-07-14