Incidental Mutation 'R7328:Lats1'
| ID |
569058 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Lats1
|
| Ensembl Gene |
ENSMUSG00000040021 |
| Gene Name |
large tumor suppressor |
| Synonyms |
|
| MMRRC Submission |
045421-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.822)
|
| Stock # |
R7328 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
10 |
| Chromosomal Location |
7556978-7592224 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to T
at 7581311 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Methionine to Leucine
at position 699
(M699L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000132078
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000040043]
[ENSMUST00000165952]
[ENSMUST00000217931]
|
| AlphaFold |
Q8BYR2 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000040043
AA Change: M699L
PolyPhen 2
Score 0.618 (Sensitivity: 0.87; Specificity: 0.91)
|
| SMART Domains |
Protein: ENSMUSP00000041915
Gene: ENSMUSG00000040021
AA Change: M699L
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:UBA
|
101 |
138 |
7.4e-11 |
PFAM |
|
low complexity region
|
228 |
267 |
N/A |
INTRINSIC |
|
low complexity region
|
301 |
314 |
N/A |
INTRINSIC |
|
low complexity region
|
371 |
379 |
N/A |
INTRINSIC |
|
low complexity region
|
433 |
445 |
N/A |
INTRINSIC |
|
low complexity region
|
482 |
493 |
N/A |
INTRINSIC |
|
low complexity region
|
520 |
530 |
N/A |
INTRINSIC |
|
low complexity region
|
554 |
559 |
N/A |
INTRINSIC |
|
S_TKc
|
704 |
1009 |
7.3e-99 |
SMART |
|
S_TK_X
|
1010 |
1081 |
1.2e-2 |
SMART |
|
low complexity region
|
1102 |
1120 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000165952
AA Change: M699L
PolyPhen 2
Score 0.618 (Sensitivity: 0.87; Specificity: 0.91)
|
| SMART Domains |
Protein: ENSMUSP00000132078
Gene: ENSMUSG00000040021
AA Change: M699L
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:UBA
|
101 |
138 |
7.4e-11 |
PFAM |
|
low complexity region
|
228 |
267 |
N/A |
INTRINSIC |
|
low complexity region
|
301 |
314 |
N/A |
INTRINSIC |
|
low complexity region
|
371 |
379 |
N/A |
INTRINSIC |
|
low complexity region
|
433 |
445 |
N/A |
INTRINSIC |
|
low complexity region
|
482 |
493 |
N/A |
INTRINSIC |
|
low complexity region
|
520 |
530 |
N/A |
INTRINSIC |
|
low complexity region
|
554 |
559 |
N/A |
INTRINSIC |
|
S_TKc
|
704 |
1009 |
7.3e-99 |
SMART |
|
S_TK_X
|
1010 |
1081 |
1.2e-2 |
SMART |
|
low complexity region
|
1102 |
1120 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000217931
AA Change: M699L
PolyPhen 2
Score 0.618 (Sensitivity: 0.87; Specificity: 0.91)
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 100.0%
- 10x: 99.7%
- 20x: 99.0%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. The N-terminal region of the protein binds CDC2 to form a complex showing reduced H1 histone kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a tumor suppressor. This is supported by studies in knockout mice showing development of soft-tissue sarcomas, ovarian stromal cell tumors and a high sensitivity to carcinogenic treatments. Two protein-coding transcripts and one non-protein coding transcript have been found for this gene. [provided by RefSeq, Jul 2012]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit high postnatal mortality, lack of mammary development, infertility, pituitary hyperplasia, reduced hormone levels, growth retardation, and susceptibility to sarcomas and ovarian stromal cell tumors. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 51 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4933427D14Rik |
C |
G |
11: 72,060,606 (GRCm39) |
|
probably null |
Het |
| Abca13 |
T |
A |
11: 9,241,545 (GRCm39) |
V1136E |
probably benign |
Het |
| Arl4c |
C |
A |
1: 88,629,239 (GRCm39) |
E50* |
probably null |
Het |
| Atxn7l1 |
T |
C |
12: 33,198,502 (GRCm39) |
|
probably null |
Het |
| Ctdsp1 |
A |
T |
1: 74,433,199 (GRCm39) |
I115F |
probably damaging |
Het |
| Cyp2j5 |
A |
G |
4: 96,551,450 (GRCm39) |
V91A |
probably damaging |
Het |
| Dscam |
T |
A |
16: 96,446,235 (GRCm39) |
K1469* |
probably null |
Het |
| Elf2 |
A |
G |
3: 51,174,198 (GRCm39) |
C110R |
probably damaging |
Het |
| Ephb1 |
A |
G |
9: 102,072,438 (GRCm39) |
Y114H |
probably damaging |
Het |
| Ephb2 |
C |
T |
4: 136,386,245 (GRCm39) |
|
probably null |
Het |
| Fbxw20 |
C |
A |
9: 109,061,383 (GRCm39) |
C122F |
probably damaging |
Het |
| Flnb |
T |
C |
14: 7,883,788 (GRCm38) |
I338T |
possibly damaging |
Het |
| Flnb |
T |
A |
14: 7,894,660 (GRCm38) |
Y819* |
probably null |
Het |
| Foxo3 |
A |
T |
10: 42,073,258 (GRCm39) |
S420T |
probably benign |
Het |
| Herpud1 |
T |
C |
8: 95,113,248 (GRCm39) |
V10A |
possibly damaging |
Het |
| Hmcn1 |
A |
T |
1: 150,514,617 (GRCm39) |
V3585E |
possibly damaging |
Het |
| Hsdl1 |
T |
C |
8: 120,292,830 (GRCm39) |
T202A |
probably benign |
Het |
| Htr1d |
G |
A |
4: 136,170,614 (GRCm39) |
S281N |
probably benign |
Het |
| Igkv14-111 |
T |
A |
6: 68,233,709 (GRCm39) |
I70N |
probably damaging |
Het |
| Igkv8-34 |
A |
G |
6: 70,021,328 (GRCm39) |
S45P |
probably damaging |
Het |
| Inha |
T |
C |
1: 75,486,760 (GRCm39) |
Y352H |
probably damaging |
Het |
| Marchf9 |
T |
C |
10: 126,894,165 (GRCm39) |
E146G |
probably damaging |
Het |
| Mcm8 |
T |
C |
2: 132,674,777 (GRCm39) |
V443A |
probably benign |
Het |
| Melk |
A |
T |
4: 44,332,931 (GRCm39) |
S296C |
probably benign |
Het |
| Myo18a |
T |
C |
11: 77,698,737 (GRCm39) |
S4P |
|
Het |
| Myof |
T |
C |
19: 37,904,847 (GRCm39) |
Y1646C |
probably damaging |
Het |
| Noc4l |
C |
A |
5: 110,796,789 (GRCm39) |
A498S |
possibly damaging |
Het |
| Nrxn3 |
T |
C |
12: 88,762,345 (GRCm39) |
S131P |
probably benign |
Het |
| Or5ae2 |
T |
C |
7: 84,506,507 (GRCm39) |
I312T |
probably benign |
Het |
| Or5ak23 |
A |
G |
2: 85,244,668 (GRCm39) |
I185T |
probably benign |
Het |
| Or5j3 |
GTACTTTTT |
GT |
2: 86,128,338 (GRCm39) |
|
probably null |
Het |
| Or8g23 |
T |
C |
9: 38,971,857 (GRCm39) |
Y35C |
probably damaging |
Het |
| Pcp4l1 |
G |
A |
1: 171,002,034 (GRCm39) |
A42V |
possibly damaging |
Het |
| Phldb2 |
T |
A |
16: 45,578,572 (GRCm39) |
|
probably null |
Het |
| Polr2b |
C |
T |
5: 77,463,846 (GRCm39) |
P81L |
probably damaging |
Het |
| Rbfa |
C |
A |
18: 80,236,454 (GRCm39) |
G215C |
probably benign |
Het |
| Rdh19 |
T |
C |
10: 127,692,896 (GRCm39) |
S188P |
probably damaging |
Het |
| Scn9a |
T |
C |
2: 66,314,931 (GRCm39) |
M1596V |
probably benign |
Het |
| Sele |
A |
T |
1: 163,876,844 (GRCm39) |
Y40F |
probably benign |
Het |
| Setd1b |
T |
A |
5: 123,290,442 (GRCm39) |
V803D |
unknown |
Het |
| Siglecf |
C |
T |
7: 43,001,691 (GRCm39) |
T167I |
possibly damaging |
Het |
| Slc39a6 |
T |
C |
18: 24,733,987 (GRCm39) |
E234G |
probably benign |
Het |
| Slco1a1 |
T |
A |
6: 141,882,134 (GRCm39) |
D145V |
possibly damaging |
Het |
| Son |
G |
A |
16: 91,455,278 (GRCm39) |
V1342I |
probably benign |
Het |
| Sybu |
G |
A |
15: 44,651,190 (GRCm39) |
P38L |
not run |
Het |
| Taf15 |
C |
T |
11: 83,375,658 (GRCm39) |
T41M |
possibly damaging |
Het |
| Tm4sf4 |
A |
T |
3: 57,333,925 (GRCm39) |
N71Y |
probably benign |
Het |
| Tm7sf2 |
C |
T |
19: 6,114,156 (GRCm39) |
V226I |
possibly damaging |
Het |
| Trim66 |
C |
A |
7: 109,056,958 (GRCm39) |
Q1066H |
probably damaging |
Het |
| Tyw1 |
T |
C |
5: 130,291,685 (GRCm39) |
V51A |
probably benign |
Het |
| Vav3 |
A |
T |
3: 109,410,744 (GRCm39) |
I192L |
probably benign |
Het |
|
| Other mutations in Lats1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00234:Lats1
|
APN |
10 |
7,567,330 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL00595:Lats1
|
APN |
10 |
7,578,069 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL00932:Lats1
|
APN |
10 |
7,588,506 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
IGL01019:Lats1
|
APN |
10 |
7,581,435 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01380:Lats1
|
APN |
10 |
7,567,544 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
IGL01965:Lats1
|
APN |
10 |
7,577,470 (GRCm39) |
missense |
probably benign |
0.10 |
|
IGL02027:Lats1
|
APN |
10 |
7,588,712 (GRCm39) |
missense |
probably benign |
|
|
IGL02611:Lats1
|
APN |
10 |
7,581,551 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
IGL02997:Lats1
|
APN |
10 |
7,578,018 (GRCm39) |
missense |
possibly damaging |
0.53 |
|
IGL03107:Lats1
|
APN |
10 |
7,588,510 (GRCm39) |
missense |
probably benign |
0.15 |
|
I1329:Lats1
|
UTSW |
10 |
7,588,566 (GRCm39) |
missense |
probably benign |
0.10 |
|
PIT4378001:Lats1
|
UTSW |
10 |
7,581,369 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0153:Lats1
|
UTSW |
10 |
7,567,339 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0568:Lats1
|
UTSW |
10 |
7,588,292 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
R0581:Lats1
|
UTSW |
10 |
7,578,705 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R0604:Lats1
|
UTSW |
10 |
7,588,425 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R1681:Lats1
|
UTSW |
10 |
7,581,678 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1694:Lats1
|
UTSW |
10 |
7,577,709 (GRCm39) |
missense |
probably benign |
0.07 |
|
R1840:Lats1
|
UTSW |
10 |
7,586,703 (GRCm39) |
nonsense |
probably null |
|
|
R1914:Lats1
|
UTSW |
10 |
7,586,221 (GRCm39) |
splice site |
probably benign |
|
|
R2137:Lats1
|
UTSW |
10 |
7,577,611 (GRCm39) |
missense |
possibly damaging |
0.71 |
|
R2317:Lats1
|
UTSW |
10 |
7,567,540 (GRCm39) |
nonsense |
probably null |
|
|
R3863:Lats1
|
UTSW |
10 |
7,581,510 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3864:Lats1
|
UTSW |
10 |
7,581,510 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4597:Lats1
|
UTSW |
10 |
7,567,510 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4657:Lats1
|
UTSW |
10 |
7,581,448 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R4658:Lats1
|
UTSW |
10 |
7,578,493 (GRCm39) |
missense |
probably benign |
|
|
R4663:Lats1
|
UTSW |
10 |
7,588,347 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4870:Lats1
|
UTSW |
10 |
7,581,549 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5101:Lats1
|
UTSW |
10 |
7,588,348 (GRCm39) |
nonsense |
probably null |
|
|
R5134:Lats1
|
UTSW |
10 |
7,567,575 (GRCm39) |
missense |
probably benign |
0.34 |
|
R5150:Lats1
|
UTSW |
10 |
7,588,415 (GRCm39) |
missense |
probably benign |
|
|
R5546:Lats1
|
UTSW |
10 |
7,581,518 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5820:Lats1
|
UTSW |
10 |
7,581,672 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6006:Lats1
|
UTSW |
10 |
7,581,359 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6301:Lats1
|
UTSW |
10 |
7,578,871 (GRCm39) |
missense |
probably benign |
0.01 |
|
R6544:Lats1
|
UTSW |
10 |
7,577,434 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R6647:Lats1
|
UTSW |
10 |
7,573,271 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R6874:Lats1
|
UTSW |
10 |
7,586,615 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7390:Lats1
|
UTSW |
10 |
7,577,859 (GRCm39) |
nonsense |
probably null |
|
|
R7438:Lats1
|
UTSW |
10 |
7,588,706 (GRCm39) |
nonsense |
probably null |
|
|
R7457:Lats1
|
UTSW |
10 |
7,586,655 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7524:Lats1
|
UTSW |
10 |
7,577,742 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R7593:Lats1
|
UTSW |
10 |
7,577,476 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7736:Lats1
|
UTSW |
10 |
7,578,128 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7884:Lats1
|
UTSW |
10 |
7,573,290 (GRCm39) |
nonsense |
probably null |
|
|
R8166:Lats1
|
UTSW |
10 |
7,577,880 (GRCm39) |
missense |
probably benign |
|
|
R8248:Lats1
|
UTSW |
10 |
7,581,667 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8458:Lats1
|
UTSW |
10 |
7,586,688 (GRCm39) |
nonsense |
probably null |
|
|
R8477:Lats1
|
UTSW |
10 |
7,581,279 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8547:Lats1
|
UTSW |
10 |
7,588,613 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9163:Lats1
|
UTSW |
10 |
7,578,052 (GRCm39) |
missense |
probably benign |
|
|
R9441:Lats1
|
UTSW |
10 |
7,578,681 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R9673:Lats1
|
UTSW |
10 |
7,588,387 (GRCm39) |
missense |
probably benign |
0.29 |
|
RF021:Lats1
|
UTSW |
10 |
7,586,372 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0026:Lats1
|
UTSW |
10 |
7,586,387 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0053:Lats1
|
UTSW |
10 |
7,567,373 (GRCm39) |
missense |
probably benign |
0.00 |
|
Z1176:Lats1
|
UTSW |
10 |
7,581,573 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- TTGCACACGTACTCACTTTGTG -3'
(R):5'- TGCTAGGATATCCCTCTCCG -3'
Sequencing Primer
(F):5'- GCACACGTACTCACTTTGTGTAGTG -3'
(R):5'- GCTTTCACATGAGCCACCTG -3'
|
| Posted On |
2019-09-13 |
Incidental Mutation