Incidental Mutation 'R6760:Timeless'
| ID |
531200 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Timeless
|
| Ensembl Gene |
ENSMUSG00000039994 |
| Gene Name |
timeless circadian clock 1 |
| Synonyms |
tim |
| MMRRC Submission |
044876-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R6760 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
10 |
| Chromosomal Location |
128067934-128088810 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 128081986 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Lysine to Arginine
at position 537
(K537R)
|
| 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: K537R
PolyPhen 2
Score 0.375 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000058021
Gene: ENSMUSG00000039994
AA Change: K537R
| 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: K537R
PolyPhen 2
Score 0.375 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000100876
Gene: ENSMUSG00000039994
AA Change: K537R
| 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: K537R
PolyPhen 2
Score 0.375 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000100878
Gene: ENSMUSG00000039994
AA Change: K537R
| 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: K537R
PolyPhen 2
Score 0.375 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000100879
Gene: ENSMUSG00000039994
AA Change: K537R
| 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: ENSMUST00000125289
|
| SMART Domains |
Protein: ENSMUSP00000132079
Gene: ENSMUSG00000039994
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:TIMELESS
|
1 |
123 |
3.6e-47 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000129147
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000142149
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000146945
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000135376
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000135538
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000136854
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000142484
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000145710
|
| Meta Mutation Damage Score |
0.1006 |
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.5%
- 10x: 97.6%
- 20x: 92.8%
|
| Validation Efficiency |
97% (35/36) |
| 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: 33 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aco1 |
C |
A |
4: 40,180,210 (GRCm39) |
C370* |
probably null |
Het |
| Akap6 |
C |
T |
12: 53,186,561 (GRCm39) |
S1325L |
probably damaging |
Het |
| Atp2a3 |
A |
G |
11: 72,873,566 (GRCm39) |
D813G |
probably damaging |
Het |
| Baz2b |
T |
A |
2: 59,792,776 (GRCm39) |
I451F |
probably benign |
Het |
| Calm2 |
T |
C |
17: 87,743,123 (GRCm39) |
D65G |
probably benign |
Het |
| Cdh23 |
C |
T |
10: 60,141,947 (GRCm39) |
V3049M |
probably damaging |
Het |
| Cfap46 |
A |
G |
7: 139,232,356 (GRCm39) |
L869P |
probably damaging |
Het |
| Chrna9 |
T |
A |
5: 66,128,571 (GRCm39) |
Y260N |
probably damaging |
Het |
| Clock |
G |
A |
5: 76,374,823 (GRCm39) |
P782L |
unknown |
Het |
| Coro2a |
A |
G |
4: 46,540,572 (GRCm39) |
M449T |
probably benign |
Het |
| Crispld1 |
T |
G |
1: 17,821,025 (GRCm39) |
V355G |
possibly damaging |
Het |
| Dnah7c |
C |
A |
1: 46,688,500 (GRCm39) |
T1890K |
probably benign |
Het |
| Dnah7c |
A |
G |
1: 46,688,511 (GRCm39) |
S1894G |
probably benign |
Het |
| Enpp5 |
G |
A |
17: 44,396,155 (GRCm39) |
G356S |
probably damaging |
Het |
| Gpr37 |
T |
C |
6: 25,669,168 (GRCm39) |
I559V |
probably benign |
Het |
| Grik5 |
A |
G |
7: 24,758,364 (GRCm39) |
|
probably null |
Het |
| Itga8 |
T |
C |
2: 12,306,451 (GRCm39) |
Y48C |
probably damaging |
Het |
| Manba |
T |
C |
3: 135,248,212 (GRCm39) |
V367A |
probably damaging |
Het |
| Mrgpra1 |
G |
A |
7: 46,984,789 (GRCm39) |
R297W |
probably benign |
Het |
| Myh7b |
C |
A |
2: 155,462,038 (GRCm39) |
Y311* |
probably null |
Het |
| Nmd3 |
T |
A |
3: 69,654,170 (GRCm39) |
|
probably null |
Het |
| Or5m9 |
T |
A |
2: 85,877,358 (GRCm39) |
C177* |
probably null |
Het |
| Pakap |
T |
C |
4: 57,856,026 (GRCm39) |
W493R |
probably damaging |
Het |
| Pcdhb11 |
A |
T |
18: 37,554,637 (GRCm39) |
|
probably benign |
Het |
| Plcb1 |
C |
T |
2: 135,313,980 (GRCm39) |
T1144M |
possibly damaging |
Het |
| Sfrp1 |
A |
G |
8: 23,901,904 (GRCm39) |
D35G |
probably damaging |
Het |
| St3gal1 |
A |
G |
15: 66,983,195 (GRCm39) |
V187A |
possibly damaging |
Het |
| Tnrc6a |
T |
A |
7: 122,771,222 (GRCm39) |
V1004E |
probably damaging |
Het |
| Tubb4a |
T |
C |
17: 57,387,796 (GRCm39) |
E410G |
possibly damaging |
Het |
| U2surp |
G |
A |
9: 95,375,764 (GRCm39) |
A143V |
probably benign |
Het |
| Vmn2r118 |
T |
A |
17: 55,899,714 (GRCm39) |
H730L |
possibly damaging |
Het |
| Vmn2r28 |
G |
A |
7: 5,484,229 (GRCm39) |
T657I |
probably damaging |
Het |
| Ybey |
A |
T |
10: 76,304,033 (GRCm39) |
N56K |
probably benign |
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 |
|
|
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 |
|
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'- AATGGCATCTTCCCCTGACTTG -3'
(R):5'- ACAGACATAGCCATGGGAGC -3'
Sequencing Primer
(F):5'- GGAAATATACAGTGCCCATTGCTGC -3'
(R):5'- CATAGCCATGGGAGCAGGGTG -3'
|
| Posted On |
2018-08-01 |
Incidental Mutation