Mutagenetix > Incidental Mutation

Incidental Mutation 'R7463:Timeless'

578573

Institutional Source

Beutler Lab

Gene Symbol

Timeless

Ensembl Gene

ENSMUSG00000039994

Gene Name

timeless circadian clock 1

Synonyms

tim

MMRRC Submission

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R7463 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

128232065-128252941 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 128250426 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 999 (S999P)

Ref Sequence

ENSEMBL: ENSMUSP00000058021 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000055539] [ENSMUST00000060782] [ENSMUST00000105242] [ENSMUST00000105243] [ENSMUST00000105244] [ENSMUST00000105245] [ENSMUST00000218722]

AlphaFold

Q9R1X4

Predicted Effect

probably benign
Transcript: ENSMUST00000055539
AA Change: S999P

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)

SMART Domains

Protein: ENSMUSP00000058021
Gene: ENSMUSG00000039994
AA Change: S999P

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

probably benign
Transcript: ENSMUST00000060782

SMART Domains

Protein: ENSMUSP00000059142
Gene: ENSMUSG00000051716

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
Pfam:Apolipo_F	50	247	2.1e-75	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105242
AA Change: S998P

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000100876
Gene: ENSMUSG00000039994
AA Change: S998P

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: S999P

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000100878
Gene: ENSMUSG00000039994
AA Change: S999P

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: S999P

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)

SMART Domains

Protein: ENSMUSP00000100879
Gene: ENSMUSG00000039994
AA Change: S999P

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

probably benign
Transcript: ENSMUST00000218722

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.4%
20x: 97.7%

Validation Efficiency

100% (62/62)

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: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc10	A	T	17: 46,323,772	V435E	probably damaging	Het
Acta2	G	A	19: 34,252,531	T8I	probably benign	Het
Adcy2	T	C	13: 68,730,280	D413G	probably damaging	Het
Adgrg6	T	A	10: 14,434,396	D727V	possibly damaging	Het
Aebp2	C	T	6: 140,637,726	Q309*	probably null	Het
Amy1	A	T	3: 113,569,884	C43*	probably null	Het
Bpifc	T	C	10: 85,979,334	E256G	probably benign	Het
Bysl	A	T	17: 47,602,471	S296T	probably benign	Het
Carmil3	C	T	14: 55,502,396	P980L	probably damaging	Het
Coch	T	A	12: 51,593,625	M1K	probably null	Het
Cpt2	A	T	4: 107,908,157	F137I	probably damaging	Het
Crem	T	C	18: 3,295,094	I112V	probably benign	Het
Cul9	A	G	17: 46,520,476		probably null	Het
Cyp3a41a	T	A	5: 145,713,564	I90F	probably damaging	Het
Cyp4f16	C	T	17: 32,550,787	A457V	possibly damaging	Het
Ddx6	A	G	9: 44,628,729	E318G	probably damaging	Het
Dip2b	A	G	15: 100,154,157	E213G	probably benign	Het
Dlx5	T	C	6: 6,878,316	H238R	probably damaging	Het
Dnaic2	A	C	11: 114,754,406	I556L	probably benign	Het
Dnmt1	C	T	9: 20,912,225	V1147M	possibly damaging	Het
Egf	G	T	3: 129,740,015	Q59K	probably benign	Het
Ermp1	A	T	19: 29,646,262	Y109*	probably null	Het
Fer1l6	T	A	15: 58,573,601	Y573*	probably null	Het
Fmnl1	T	C	11: 103,193,128	L503P	probably damaging	Het
Gnptab	T	G	10: 88,431,389	I447M	probably damaging	Het
Hgf	G	A	5: 16,578,450	D253N	probably benign	Het
Hjurp	CTCTGGGAGGGCTTGCTCCGGGGGCAGTGTGTCCTGTTCTTGTGCAGCCCCT	C	1: 88,266,277		probably benign	Het
Igf2r	T	C	17: 12,710,645	T958A	probably benign	Het
Kcnd2	T	A	6: 21,216,498	L67Q	probably damaging	Het
Kif5a	A	G	10: 127,243,724	V248A	probably damaging	Het
Krt33b	A	G	11: 100,029,563	I88T	probably damaging	Het
Lhx2	G	A	2: 38,351,846	E25K	possibly damaging	Het
Mex3d	C	T	10: 80,381,698	G562R		Het
Myom2	A	T	8: 15,117,679	Y1088F	probably null	Het
Ncapg	T	A	5: 45,694,092		probably null	Het
Nudc	A	C	4: 133,534,403	V190G	possibly damaging	Het
Obscn	G	T	11: 59,122,860	R1054S	probably benign	Het
Olfr1045	T	C	2: 86,197,838	M305V	probably benign	Het
Olfr1510	A	G	14: 52,410,711	W54R	probably benign	Het
Olfr651	T	C	7: 104,553,482	S188P	possibly damaging	Het
Olfr683	T	A	7: 105,143,937	M119L	probably benign	Het
Olfr710	A	T	7: 106,944,173	V276E	probably damaging	Het
Olfr979	A	G	9: 40,000,564	V221A	probably benign	Het
Pcdh10	A	T	3: 45,383,572	R891S	possibly damaging	Het
Pcdh15	C	T	10: 74,631,770	S1873L	possibly damaging	Het
Pcdh7	A	G	5: 57,720,998	K632E	probably benign	Het
Pcdhgb8	G	A	18: 37,763,427	A517T	probably damaging	Het
Ptgr2	A	T	12: 84,292,298		probably benign	Het
Ptpn18	G	A	1: 34,473,364	D417N	possibly damaging	Het
Racgap1	T	A	15: 99,642,958	T4S	probably benign	Het
Rb1cc1	A	G	1: 6,249,180	H941R	probably benign	Het
Reln	T	C	5: 22,103,435	H312R	probably damaging	Het
Rnf166	T	A	8: 122,467,987	H208L	probably damaging	Het
Theg	T	C	10: 79,576,715	E314G	probably damaging	Het
Tmem94	G	T	11: 115,786,256	R118L	possibly damaging	Het
Tor1aip1	A	T	1: 156,007,609	H349Q	possibly damaging	Het
Ttn	T	A	2: 76,920,460	E3415V	probably benign	Het
Vmn2r102	A	T	17: 19,676,624	N78Y	probably damaging	Het
Wdr11	A	T	7: 129,607,086	D427V	probably damaging	Het
Zer1	A	T	2: 30,113,437		probably benign	Het
Zfp516	T	A	18: 82,957,108	M477K	probably benign	Het

Other mutations in Timeless

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00091:Timeless	APN	10	128241708	missense	probably damaging	1.00
IGL02157:Timeless	APN	10	128242386	missense	probably benign	0.01
IGL02300:Timeless	APN	10	128244807	missense	probably benign	0.00
IGL02587:Timeless	APN	10	128239916	missense	probably damaging	0.99
IGL02588:Timeless	APN	10	128243334	missense	probably damaging	1.00
IGL02892:Timeless	APN	10	128244251	missense	probably damaging	1.00
IGL02930:Timeless	APN	10	128247191	missense	probably benign	0.00
IGL02986:Timeless	APN	10	128249760	missense	possibly damaging	0.82
IGL03345:Timeless	APN	10	128247586	missense	probably benign	0.04
IGL03393:Timeless	APN	10	128252055	missense	probably damaging	1.00
R0388:Timeless	UTSW	10	128241425	splice site	probably null
R0607:Timeless	UTSW	10	128246334	missense	probably benign
R0638:Timeless	UTSW	10	128244673	nonsense	probably null
R0734:Timeless	UTSW	10	128250060	missense	probably damaging	1.00
R1346:Timeless	UTSW	10	128242365	missense	possibly damaging	0.83
R1625:Timeless	UTSW	10	128240624	missense	probably damaging	0.99
R1771:Timeless	UTSW	10	128247608	missense	probably benign	0.11
R1860:Timeless	UTSW	10	128246114	missense	probably benign	0.00
R1920:Timeless	UTSW	10	128241714	missense	probably damaging	1.00
R1988:Timeless	UTSW	10	128244187	missense	probably damaging	0.98
R2981:Timeless	UTSW	10	128248458	missense	probably benign	0.34
R4359:Timeless	UTSW	10	128247342	missense	probably benign	0.00
R4647:Timeless	UTSW	10	128239956	missense	possibly damaging	0.80
R4753:Timeless	UTSW	10	128240020	utr 5 prime	probably benign
R4868:Timeless	UTSW	10	128247361	missense	probably benign
R4901:Timeless	UTSW	10	128250762	missense	probably damaging	1.00
R4956:Timeless	UTSW	10	128241651	missense	probably damaging	1.00
R5341:Timeless	UTSW	10	128247178	missense	possibly damaging	0.81
R5439:Timeless	UTSW	10	128241735	missense	probably damaging	1.00
R5585:Timeless	UTSW	10	128240243	missense	probably damaging	0.97
R5842:Timeless	UTSW	10	128247459	critical splice donor site	probably null
R5843:Timeless	UTSW	10	128244244	splice site	probably null
R6005:Timeless	UTSW	10	128244200	missense	probably damaging	0.99
R6271:Timeless	UTSW	10	128250724	missense	probably damaging	1.00
R6558:Timeless	UTSW	10	128249563	missense	probably benign	0.01
R6694:Timeless	UTSW	10	128239999	critical splice donor site	probably null
R6738:Timeless	UTSW	10	128240635	missense	probably damaging	1.00
R6760:Timeless	UTSW	10	128246117	missense	probably benign	0.38
R7213:Timeless	UTSW	10	128243289	missense	probably benign
R7248:Timeless	UTSW	10	128252001	missense	probably benign
R7345:Timeless	UTSW	10	128249754	missense	probably damaging	1.00
R7513:Timeless	UTSW	10	128249530	missense	probably damaging	0.99
R7574:Timeless	UTSW	10	128244669	missense	probably damaging	1.00
R8220:Timeless	UTSW	10	128246396	missense	probably damaging	0.98
R8418:Timeless	UTSW	10	128250736	missense	probably benign	0.02
R8742:Timeless	UTSW	10	128247238	missense	probably benign	0.00
R8765:Timeless	UTSW	10	128244543	critical splice donor site	probably null
R9508:Timeless	UTSW	10	128240227	missense	probably benign	0.01
X0028:Timeless	UTSW	10	128250325	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- TTCCATGGGTGTACAGAAACCAG -3'
(R):5'- GTCATTTGCTGCTCGGATCAG -3'

Sequencing Primer
(F):5'- GAGGCCATTTTCTCATCCGTGTG -3'
(R):5'- TCGGATCAGGGAGCTCTG -3'

Posted On

2019-10-07