Incidental Mutation 'R0581:Lats1'
| ID |
56429 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Lats1
|
| Ensembl Gene |
ENSMUSG00000040021 |
| Gene Name |
large tumor suppressor |
| Synonyms |
|
| MMRRC Submission |
038771-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.822)
|
| Stock # |
R0581 (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 7578705 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Alanine
at position 610
(T610A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000151533
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000040043]
[ENSMUST00000165952]
[ENSMUST00000217931]
|
| AlphaFold |
Q8BYR2 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000040043
AA Change: T610A
PolyPhen 2
Score 0.668 (Sensitivity: 0.86; Specificity: 0.91)
|
| SMART Domains |
Protein: ENSMUSP00000041915
Gene: ENSMUSG00000040021
AA Change: T610A
| 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: T610A
PolyPhen 2
Score 0.668 (Sensitivity: 0.86; Specificity: 0.91)
|
| SMART Domains |
Protein: ENSMUSP00000132078
Gene: ENSMUSG00000040021
AA Change: T610A
| 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: T610A
PolyPhen 2
Score 0.668 (Sensitivity: 0.86; Specificity: 0.91)
|
| Meta Mutation Damage Score |
0.0697 |
| Coding Region Coverage |
- 1x: 99.7%
- 3x: 99.0%
- 10x: 97.3%
- 20x: 93.7%
|
| Validation Efficiency |
95% (42/44) |
| 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: 40 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Akap9 |
A |
G |
5: 4,100,620 (GRCm39) |
T2761A |
probably benign |
Het |
| Apold1 |
G |
A |
6: 134,960,776 (GRCm39) |
V77I |
probably benign |
Het |
| Atad2 |
T |
C |
15: 57,990,060 (GRCm39) |
T139A |
probably benign |
Het |
| Cacna1a |
A |
T |
8: 85,328,565 (GRCm39) |
I1668F |
possibly damaging |
Het |
| Ccer2 |
T |
A |
7: 28,456,451 (GRCm39) |
|
probably benign |
Het |
| Cyp2c54 |
T |
A |
19: 40,035,999 (GRCm39) |
T304S |
probably benign |
Het |
| Dpp4 |
T |
A |
2: 62,187,020 (GRCm39) |
M497L |
probably benign |
Het |
| Evpl |
T |
A |
11: 116,120,316 (GRCm39) |
I541L |
probably benign |
Het |
| Ggn |
A |
G |
7: 28,871,729 (GRCm39) |
T370A |
probably benign |
Het |
| Ghr |
A |
G |
15: 3,418,116 (GRCm39) |
|
probably benign |
Het |
| Gm6605 |
C |
A |
7: 38,147,699 (GRCm39) |
|
noncoding transcript |
Het |
| Gpr68 |
G |
C |
12: 100,844,815 (GRCm39) |
P243R |
probably damaging |
Het |
| Gtf3c2 |
G |
T |
5: 31,316,862 (GRCm39) |
Y720* |
probably null |
Het |
| Il2rb |
T |
A |
15: 78,366,136 (GRCm39) |
Y387F |
possibly damaging |
Het |
| Kcnu1 |
T |
A |
8: 26,427,529 (GRCm39) |
V282E |
probably damaging |
Het |
| Krt222 |
G |
A |
11: 99,127,018 (GRCm39) |
Q201* |
probably null |
Het |
| Mroh2a |
GT |
GTT |
1: 88,183,888 (GRCm39) |
|
probably null |
Het |
| Myh7 |
T |
C |
14: 55,222,953 (GRCm39) |
I751V |
probably benign |
Het |
| Mypn |
A |
G |
10: 62,998,023 (GRCm39) |
I429T |
probably benign |
Het |
| Nemf |
A |
T |
12: 69,369,045 (GRCm39) |
D723E |
probably benign |
Het |
| Nlrp4b |
T |
C |
7: 10,448,457 (GRCm39) |
L220P |
probably damaging |
Het |
| Npr3 |
T |
A |
15: 11,851,536 (GRCm39) |
D418V |
probably damaging |
Het |
| Nsd3 |
A |
G |
8: 26,200,718 (GRCm39) |
N1270S |
probably damaging |
Het |
| Or1j15 |
T |
C |
2: 36,458,834 (GRCm39) |
S75P |
probably damaging |
Het |
| Or2g1 |
A |
G |
17: 38,106,993 (GRCm39) |
I219M |
probably damaging |
Het |
| Otogl |
G |
A |
10: 107,624,901 (GRCm39) |
T1579I |
possibly damaging |
Het |
| Pkp2 |
T |
A |
16: 16,087,647 (GRCm39) |
|
probably benign |
Het |
| Psd3 |
T |
C |
8: 68,173,598 (GRCm39) |
Y301C |
probably damaging |
Het |
| Psmb4 |
T |
C |
3: 94,793,479 (GRCm39) |
H134R |
probably damaging |
Het |
| Ralgapb |
A |
G |
2: 158,334,881 (GRCm39) |
T1043A |
probably benign |
Het |
| Sec14l5 |
T |
A |
16: 4,996,349 (GRCm39) |
|
probably null |
Het |
| Serpina12 |
T |
A |
12: 103,997,399 (GRCm39) |
Q374L |
probably damaging |
Het |
| Serpinb10 |
C |
T |
1: 107,474,692 (GRCm39) |
R362* |
probably null |
Het |
| Sorcs1 |
T |
A |
19: 50,241,139 (GRCm39) |
I416F |
possibly damaging |
Het |
| Sparcl1 |
T |
C |
5: 104,241,178 (GRCm39) |
D82G |
probably damaging |
Het |
| Stat6 |
A |
T |
10: 127,483,985 (GRCm39) |
Q89L |
probably damaging |
Het |
| Tat |
A |
G |
8: 110,718,270 (GRCm39) |
T52A |
possibly damaging |
Het |
| Yipf7 |
T |
A |
5: 69,678,406 (GRCm39) |
I128F |
probably benign |
Het |
| Zfp112 |
T |
A |
7: 23,825,288 (GRCm39) |
C419S |
probably damaging |
Het |
| Zzef1 |
A |
G |
11: 72,742,726 (GRCm39) |
I769V |
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 |
|
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 |
|
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'- AGTTCAGACTGTTCAGCCTACCCC -3'
(R):5'- ATGCAGACGCTGCTGATGAGAC -3'
Sequencing Primer
(F):5'- ACCTGTTGCTGAAGCTCCAAG -3'
(R):5'- CTGCTGATGAGACTTCAGGAC -3'
|
| Posted On |
2013-07-11 |
Incidental Mutation