Mutagenetix > Incidental Mutation

Incidental Mutation 'R4868:Timeless'

376340

Institutional Source

Beutler Lab

Gene Symbol

Timeless

Ensembl Gene

ENSMUSG00000039994

Gene Name

timeless circadian clock 1

Synonyms

tim

MMRRC Submission

042478-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4868 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

128067934-128088810 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 128083230 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Valine at position 659 (G659V)

Ref Sequence

ENSEMBL: ENSMUSP00000100879 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000055539] [ENSMUST00000105242] [ENSMUST00000105243] [ENSMUST00000105244] [ENSMUST00000105245]

AlphaFold

Q9R1X4

Predicted Effect

probably benign
Transcript: ENSMUST00000055539
AA Change: G659V

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000058021
Gene: ENSMUSG00000039994
AA Change: G659V

Domain	Start	End	E-Value	Type
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: G659V

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000100876
Gene: ENSMUSG00000039994
AA Change: G659V

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
Pfam:TIMELESS	21	285	7.8e-104	PFAM
low complexity region	381	395	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105244
AA Change: G659V

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000100878
Gene: ENSMUSG00000039994
AA Change: G659V

Domain	Start	End	E-Value	Type
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: G659V

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000100879
Gene: ENSMUSG00000039994
AA Change: G659V

Domain	Start	End	E-Value	Type
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: ENSMUST00000129147

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145710

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000142484

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135376

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000142149

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146945

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000136854

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.1%
20x: 94.7%

Validation Efficiency

99% (91/92)

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: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933405L10Rik	A	G	8: 106,436,729 (GRCm39)	*299W	probably null	Het
4933412E24Rik	G	A	15: 59,887,817 (GRCm39)	L208F	possibly damaging	Het
Abca8b	G	A	11: 109,865,338 (GRCm39)	A373V	probably benign	Het
Actn3	A	T	19: 4,914,482 (GRCm39)	W549R	probably benign	Het
Adamts4	C	T	1: 171,080,000 (GRCm39)		probably benign	Het
Adcy4	T	C	14: 56,011,179 (GRCm39)	I615V	probably benign	Het
Akap1	A	G	11: 88,735,379 (GRCm39)	S428P	possibly damaging	Het
Akap13	A	T	7: 75,393,252 (GRCm39)	R2476W	probably damaging	Het
Alx3	A	G	3: 107,507,943 (GRCm39)	S151G	possibly damaging	Het
Aoah	T	A	13: 21,099,151 (GRCm39)	Y243*	probably null	Het
Asap1	A	G	15: 63,966,030 (GRCm39)	V1025A	probably benign	Het
Atp8b1	A	T	18: 64,684,937 (GRCm39)	I728N	probably damaging	Het
Baz2b	C	A	2: 59,755,226 (GRCm39)	V1001L	possibly damaging	Het
Bmpr2	T	A	1: 59,909,615 (GRCm39)	S1030T	probably benign	Het
Cacna2d3	A	T	14: 28,678,743 (GRCm39)		probably null	Het
Casp3	A	T	8: 47,087,314 (GRCm39)	N87I	probably benign	Het
Ccdc171	T	A	4: 83,612,569 (GRCm39)	L995Q	probably damaging	Het
Ccdc80	T	A	16: 44,924,776 (GRCm39)	Y637N	probably damaging	Het
Ccr4	A	G	9: 114,321,901 (GRCm39)	F55L	probably benign	Het
Cmah	T	A	13: 24,648,247 (GRCm39)	V494E	probably damaging	Het
Cnot6l	A	G	5: 96,230,882 (GRCm39)	Y362H	probably damaging	Het
Coq6	T	C	12: 84,417,726 (GRCm39)	V222A	probably damaging	Het
Ctdspl2	C	A	2: 121,823,879 (GRCm39)	T240N	possibly damaging	Het
D430041D05Rik	T	C	2: 104,085,754 (GRCm39)	T248A	possibly damaging	Het
Dctn6	A	T	8: 34,559,230 (GRCm39)		probably benign	Het
Dhx34	T	C	7: 15,933,727 (GRCm39)	D955G	probably benign	Het
Dnaaf5	A	G	5: 139,155,941 (GRCm39)	M541V	probably benign	Het
Dnah17	A	T	11: 117,999,038 (GRCm39)	S912T	probably benign	Het
Dnah2	A	T	11: 69,354,474 (GRCm39)	V2248E	probably damaging	Het
Dysf	T	C	6: 84,156,675 (GRCm39)	W1502R	probably damaging	Het
Dzip1	A	T	14: 119,114,626 (GRCm39)	V843E	probably damaging	Het
Esp23	G	T	17: 39,384,915 (GRCm39)	T27K	probably benign	Het
Esp3	A	T	17: 40,944,420 (GRCm39)	M21L	possibly damaging	Het
Fam43b	T	A	4: 138,123,108 (GRCm39)	T71S	probably benign	Het
Fpgs	G	A	2: 32,582,673 (GRCm39)	R63C	probably damaging	Het
H2-M11	G	T	17: 36,859,811 (GRCm39)	W268L	probably damaging	Het
Inpp5b	T	C	4: 124,645,203 (GRCm39)	S210P	probably damaging	Het
Itsn1	T	A	16: 91,582,205 (GRCm39)	S51T	probably damaging	Het
Kctd2	G	A	11: 115,320,205 (GRCm39)	V246I	probably damaging	Het
Krt75	C	T	15: 101,476,556 (GRCm39)	G403E	probably damaging	Het
Lamp3	T	A	16: 19,520,040 (GRCm39)	T48S	probably benign	Het
Lyzl4	C	A	9: 121,412,075 (GRCm39)	V114L	probably damaging	Het
Maml3	C	A	3: 52,011,345 (GRCm39)	E74*	probably null	Het
Map2k7	G	A	8: 4,297,751 (GRCm39)		probably benign	Het
Mapk8ip3	A	G	17: 25,120,389 (GRCm39)	V883A	probably benign	Het
Mbtps1	C	T	8: 120,235,667 (GRCm39)	V1004I	probably benign	Het
Metap1	G	T	3: 138,188,850 (GRCm39)	H48Q	probably damaging	Het
Mical2	T	A	7: 111,917,831 (GRCm39)	V396E	probably damaging	Het
Mks1	T	A	11: 87,744,549 (GRCm39)		probably benign	Het
Ndst1	T	C	18: 60,828,548 (GRCm39)	T669A	probably benign	Het
Obox3	T	C	7: 15,361,235 (GRCm39)	K10R	probably damaging	Het
Opn3	T	C	1: 175,491,127 (GRCm39)	Y302C	probably damaging	Het
Or4f62	T	A	2: 111,986,916 (GRCm39)	S207T	probably damaging	Het
Or6b6	C	T	7: 106,570,974 (GRCm39)	M192I	probably benign	Het
Or9g8	T	G	2: 85,606,970 (GRCm39)	V14G	possibly damaging	Het
Pdzph1	A	T	17: 59,281,751 (GRCm39)	V177D	probably benign	Het
Pex5l	T	A	3: 33,006,639 (GRCm39)	I577F	probably damaging	Het
Pmpcb	T	A	5: 21,953,851 (GRCm39)	Y366*	probably null	Het
Prr14l	A	T	5: 32,987,281 (GRCm39)	M738K	probably benign	Het
Prx	T	C	7: 27,217,004 (GRCm39)	S641P	probably benign	Het
Ptchd3	A	G	11: 121,721,883 (GRCm39)	Y252C	possibly damaging	Het
Reg3a	A	G	6: 78,358,883 (GRCm39)	E27G	probably damaging	Het
Ripor2	A	G	13: 24,878,124 (GRCm39)	T300A	possibly damaging	Het
Sdf4	T	A	4: 156,093,642 (GRCm39)	S259T	probably damaging	Het
Sike1	A	G	3: 102,904,730 (GRCm39)		probably null	Het
Sis	T	G	3: 72,850,881 (GRCm39)	I606L	probably benign	Het
Slc30a9	T	C	5: 67,482,026 (GRCm39)	I94T	probably benign	Het
Slc5a4a	T	C	10: 76,014,065 (GRCm39)	I424T	probably damaging	Het
Spx	C	T	6: 142,362,116 (GRCm39)	R72*	probably null	Het
St7	C	A	6: 17,819,265 (GRCm39)	N56K	probably damaging	Het
Tcte2	C	A	17: 13,948,270 (GRCm39)	G3V	probably damaging	Het
Tent5b	A	G	4: 133,213,393 (GRCm39)		probably null	Het
Tgfb3	T	C	12: 86,108,955 (GRCm39)	D258G	probably benign	Het
Tnn	T	C	1: 159,958,443 (GRCm39)	R467G	possibly damaging	Het
Tor1b	T	C	2: 30,846,589 (GRCm39)		probably null	Het
Trank1	T	A	9: 111,194,709 (GRCm39)	L911Q	probably damaging	Het
Ttll2	C	T	17: 7,618,998 (GRCm39)	V310I	probably benign	Het
Ttyh3	A	T	5: 140,615,221 (GRCm39)	I389N	probably damaging	Het
Tut4	T	C	4: 108,406,417 (GRCm39)		probably benign	Het
Ube3b	T	C	5: 114,536,488 (GRCm39)	V216A	probably benign	Het
Vezf1	T	A	11: 87,965,520 (GRCm39)	V254E	probably damaging	Het
Vmn1r122	T	C	7: 20,867,227 (GRCm39)	E276G	probably benign	Het
Vmn1r167	T	A	7: 23,204,161 (GRCm39)	N285I	probably benign	Het
Vmn2r45	T	A	7: 8,484,480 (GRCm39)	I442F	probably benign	Het
Vwa8	C	A	14: 79,420,522 (GRCm39)	A1741E	probably damaging	Het
Wdr20	T	A	12: 110,704,668 (GRCm39)	V69E	probably damaging	Het
Xkr4	T	G	1: 3,287,074 (GRCm39)	Q372P	probably damaging	Het

Other mutations in Timeless

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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'- GCCTGAAGGAAATGCGTTTGG -3'
(R):5'- CAGAGGGAAATTATTCAGCACTGG -3'

Sequencing Primer
(F):5'- AAGGAAATGCGTTTGGCTCTCC -3'
(R):5'- TTATTCAGCACTGGACAGAGACTGC -3'

Posted On

2016-03-17