Incidental Mutation 'R4870:Lats1'
| ID |
376510 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Lats1
|
| Ensembl Gene |
ENSMUSG00000040021 |
| Gene Name |
large tumor suppressor |
| Synonyms |
|
| MMRRC Submission |
042480-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.822)
|
| Stock # |
R4870 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
10 |
| Chromosomal Location |
7556978-7592224 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 7581549 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Cysteine
at position 778
(Y778C)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000151533
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000040043]
[ENSMUST00000165952]
[ENSMUST00000217931]
|
| AlphaFold |
Q8BYR2 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000040043
AA Change: Y778C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000041915
Gene: ENSMUSG00000040021
AA Change: Y778C
| 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 |
probably damaging
Transcript: ENSMUST00000165952
AA Change: Y778C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000132078
Gene: ENSMUSG00000040021
AA Change: Y778C
| 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 |
probably damaging
Transcript: ENSMUST00000217931
AA Change: Y778C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| Meta Mutation Damage Score |
0.9504 |
| Coding Region Coverage |
- 1x: 99.1%
- 3x: 98.5%
- 10x: 96.9%
- 20x: 94.1%
|
| Validation Efficiency |
100% (77/77) |
| 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: 68 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abcb11 |
A |
T |
2: 69,069,540 (GRCm39) |
I1285N |
probably damaging |
Het |
| Abcc8 |
G |
A |
7: 45,756,683 (GRCm39) |
R721* |
probably null |
Het |
| Alox8 |
T |
C |
11: 69,077,394 (GRCm39) |
Y423C |
probably damaging |
Het |
| Ankle2 |
T |
A |
5: 110,399,344 (GRCm39) |
|
probably null |
Het |
| Cdc14a |
A |
G |
3: 116,217,109 (GRCm39) |
I9T |
probably benign |
Het |
| Ceacam18 |
T |
C |
7: 43,291,328 (GRCm39) |
C257R |
probably damaging |
Het |
| Cilp |
T |
C |
9: 65,186,980 (GRCm39) |
V1025A |
probably damaging |
Het |
| Clcn7 |
G |
T |
17: 25,372,539 (GRCm39) |
|
probably benign |
Het |
| Csnk1d |
A |
T |
11: 120,874,014 (GRCm39) |
|
probably benign |
Het |
| Cyp11b2 |
A |
G |
15: 74,724,995 (GRCm39) |
S285P |
probably benign |
Het |
| Dip2b |
T |
A |
15: 100,093,665 (GRCm39) |
|
probably null |
Het |
| Dmrt1 |
T |
A |
19: 25,483,219 (GRCm39) |
M1K |
probably null |
Het |
| Dnajc14 |
T |
C |
10: 128,653,219 (GRCm39) |
V684A |
probably benign |
Het |
| Dnmt3b |
A |
G |
2: 153,512,284 (GRCm39) |
Q335R |
probably benign |
Het |
| Exoc3l2 |
T |
A |
7: 19,229,117 (GRCm39) |
C772S |
unknown |
Het |
| F2rl1 |
A |
T |
13: 95,650,492 (GRCm39) |
F130Y |
probably damaging |
Het |
| Galk2 |
C |
G |
2: 125,771,557 (GRCm39) |
S194* |
probably null |
Het |
| Garre1 |
C |
A |
7: 33,984,312 (GRCm39) |
V104L |
possibly damaging |
Het |
| Gpbp1l1 |
A |
G |
4: 116,430,714 (GRCm39) |
T62A |
probably benign |
Het |
| H2-Q10 |
A |
T |
17: 35,781,357 (GRCm39) |
D53V |
probably damaging |
Het |
| H2-T22 |
T |
C |
17: 36,349,924 (GRCm39) |
K356R |
probably benign |
Het |
| Insrr |
G |
A |
3: 87,718,911 (GRCm39) |
V956M |
probably damaging |
Het |
| Ints7 |
A |
G |
1: 191,328,443 (GRCm39) |
T239A |
probably damaging |
Het |
| Isl1 |
A |
G |
13: 116,444,806 (GRCm39) |
|
probably benign |
Het |
| Kcng2 |
A |
G |
18: 80,366,083 (GRCm39) |
C90R |
probably benign |
Het |
| Kif3c |
C |
T |
12: 3,451,735 (GRCm39) |
P171S |
probably damaging |
Het |
| Knl1 |
A |
G |
2: 118,911,994 (GRCm39) |
T1704A |
probably benign |
Het |
| Limd2 |
T |
C |
11: 106,050,215 (GRCm39) |
M1V |
probably null |
Het |
| Mcm10 |
A |
T |
2: 5,008,970 (GRCm39) |
I333N |
probably damaging |
Het |
| Mipep |
T |
A |
14: 61,040,329 (GRCm39) |
L283* |
probably null |
Het |
| Mixl1 |
A |
G |
1: 180,522,237 (GRCm39) |
S215P |
probably benign |
Het |
| Mmp21 |
A |
G |
7: 133,280,406 (GRCm39) |
L188P |
probably damaging |
Het |
| Mob1a |
T |
C |
6: 83,317,221 (GRCm39) |
S213P |
probably benign |
Het |
| Mplkipl1 |
C |
T |
19: 61,164,364 (GRCm39) |
G24R |
unknown |
Het |
| Ndufaf6 |
T |
C |
4: 11,060,917 (GRCm39) |
T220A |
probably benign |
Het |
| Nr4a3 |
A |
T |
4: 48,051,651 (GRCm39) |
Y135F |
possibly damaging |
Het |
| Ntn1 |
CCTTCTTCT |
CCTTCT |
11: 68,103,852 (GRCm39) |
|
probably benign |
Het |
| Obscn |
A |
T |
11: 59,027,032 (GRCm39) |
L57Q |
probably damaging |
Het |
| Or52e19b |
T |
A |
7: 103,032,840 (GRCm39) |
D123V |
probably damaging |
Het |
| Or5d35 |
T |
C |
2: 87,855,804 (GRCm39) |
L246P |
probably damaging |
Het |
| Pirb |
T |
A |
7: 3,715,661 (GRCm39) |
M839L |
probably benign |
Het |
| Plcl2 |
A |
G |
17: 50,914,254 (GRCm39) |
E421G |
possibly damaging |
Het |
| Ppp1r12b |
T |
C |
1: 134,876,771 (GRCm39) |
N99S |
probably benign |
Het |
| Ptpro |
A |
G |
6: 137,354,130 (GRCm39) |
K169E |
probably damaging |
Het |
| Rita1 |
T |
A |
5: 120,749,448 (GRCm39) |
K88N |
probably damaging |
Het |
| Rptn |
A |
T |
3: 93,303,776 (GRCm39) |
K370* |
probably null |
Het |
| Simc1 |
A |
G |
13: 54,687,576 (GRCm39) |
D115G |
probably null |
Het |
| Stab1 |
T |
A |
14: 30,864,000 (GRCm39) |
N136I |
probably benign |
Het |
| Syt4 |
T |
A |
18: 31,580,409 (GRCm39) |
|
probably benign |
Het |
| Sytl2 |
A |
T |
7: 90,038,106 (GRCm39) |
N522I |
probably damaging |
Het |
| Tax1bp1 |
A |
G |
6: 52,706,478 (GRCm39) |
|
probably benign |
Het |
| Tenm2 |
A |
T |
11: 35,969,396 (GRCm39) |
D847E |
probably damaging |
Het |
| Th |
G |
T |
7: 142,447,834 (GRCm39) |
D321E |
probably benign |
Het |
| Tmem44 |
A |
T |
16: 30,359,591 (GRCm39) |
L46Q |
probably damaging |
Het |
| Trp53bp1 |
A |
G |
2: 121,087,122 (GRCm39) |
L178P |
probably damaging |
Het |
| Trp63 |
A |
G |
16: 25,684,968 (GRCm39) |
*285W |
probably null |
Het |
| Tsen34 |
T |
C |
7: 3,697,380 (GRCm39) |
|
probably benign |
Het |
| Tssk4 |
C |
T |
14: 55,889,272 (GRCm39) |
T256I |
probably benign |
Het |
| Ttc17 |
A |
T |
2: 94,196,954 (GRCm39) |
N464K |
probably damaging |
Het |
| Ttll2 |
C |
T |
17: 7,618,998 (GRCm39) |
V310I |
probably benign |
Het |
| Ubn1 |
A |
G |
16: 4,895,177 (GRCm39) |
E741G |
probably damaging |
Het |
| Urad |
T |
A |
5: 147,252,264 (GRCm39) |
I63F |
probably damaging |
Het |
| Vcan |
T |
C |
13: 89,852,858 (GRCm39) |
T701A |
probably benign |
Het |
| Vmn2r58 |
A |
G |
7: 41,486,639 (GRCm39) |
V752A |
possibly damaging |
Het |
| Vmn2r69 |
C |
A |
7: 85,060,793 (GRCm39) |
V264L |
possibly damaging |
Het |
| Zfp292 |
A |
G |
4: 34,808,917 (GRCm39) |
S1376P |
probably damaging |
Het |
| Zfp955a |
G |
A |
17: 33,460,699 (GRCm39) |
R478* |
probably null |
Het |
| Znfx1 |
A |
C |
2: 166,897,189 (GRCm39) |
F578L |
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 |
|
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 |
|
R7328:Lats1
|
UTSW |
10 |
7,581,311 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
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'- TGGTGAAGTCTGTCTAGCAAG -3'
(R):5'- GTGCACAAGCCAAAGTCAGTC -3'
Sequencing Primer
(F):5'- GTCTGTCTAGCAAGAAAAGTCGATAC -3'
(R):5'- GTCAATTTAATATGGCCATCACGGTC -3'
|
| Posted On |
2016-03-17 |
Incidental Mutation